|ABSTRACTS OF DIACAN-12
|Year : 2013 | Volume
| Issue : 3 | Page : 164-201
Abstracts of DIACAN-12
|Date of Web Publication||10-Jul-2013|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Abstracts of DIACAN-12. Int J Nutr Pharmacol Neurol Dis 2013;3:164-201
| Plenary Lectures|| |
Bioactivities from tropical plants with traditional uses
M. S. Kanthimathi
Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia. E-mail: [email protected]
Two woody herbaceous plants in local forests, Cyrtandra cupulata (Gesneriaceae) and Apama tomentosa (Aristolochiaceae) were found to have substantial anti-oxidant activity on extraction with a series of solvents. Crude and purified compounds also showed anti-cancer activity; C. cupulata, against the breast cancer cell line, MCF-7 and A. tomentosa, against the ovarian cancer cell line, CaOv-3. The purified active compound from C. cupulata, beta-sitosterol, showed apoptotic activity against MCF-7, and also exhibited wound healing properties (by re-epithelialization of rat skin fibroblasts), enhanced lipogenesis in rat pre-adipocytes, and enhanced lipolysis and glucose uptake in rat adipocytes. The active compound from A. tomentosa, palmitone, exhibited apoptotic activity against CaOv-3, and increased the level of anti-oxidant enzymes (xanthine oxidase, glutathione peroxidase, and catalase) in the same cell line. Parts of these plants are used by the "orang asli" (aboriginal people) traditionally, as contraceptives, and also as post-natal tonics and anti-inflammatory agents. Though various genera of these plants are found in Asia and the Pacific rim, and their ethno-pharmacological benefits have been documented, these have not been substantiated by published scientific data. This is the first scientifically documented investigation of the various activities mentioned above.
Phytopharmacological studies of some medicinal plants of Bangladesh with special emphasis to anti-diabetic drug discovery
Mohammad A. Rashid, Mohammad A. Kaisar, Mohammad R. Haque, Md. Al Amin Sikder
Department of Pharmaceutical Chemistry, Phytochemical Research Laboratory, Faculty of Pharmacy, University of Dhaka, Dhaka-1000, Bangladesh. E-mail: [email protected]
Diabetes mellitus, or simply diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin or because cells do not respond to the insulin that is produced. In 2010, the International Diabetes Federation estimated that 5.7 million (6.1%) and 6.7 million (7.1%) of people living in Bangladesh are suffering from diabetes and impaired glucose tolerance, respectively. By 2030, this number of diabetic population is expected to rise to 11.1 million. Natural products, especially those derived from higher plants, have attracted scientists from ancient time because of their potential therapeutic values, including anti-diabetic activity. Drug development from natural sources showed that natural products or natural product-derived drugs comprised about 28% of all new chemical entities launched to the market. These are originated from terrestrial plants, microbes, marine organisms, etc. However, until recently, an insignificant part of the plants has been scientifically evaluated for their medicinal properties. Bangladesh is a rich repository of medicinal plants, many of which are widely used in the Ayurvedic, Unani, Herbal, and other traditional systems of medicines. Thus, our study programs were initiated to investigate some of the traditionally used medicinal plants of Bangladesh including, Andrographis paniculata, Anthocephalus chinensis, Sesbania sesban, Moringa oleifera, and Syzygium cumini in order to isolate and identify the bioactive compounds. The samples were collected, properly authenticated, and then extracted with solvents of various polarities. The concentrated extractives were subjected to repeated separation and purification processes, including high performance liquid chromatography. The structures of the purified molecules were elucidated by extensive spectroscopic studies and chemical derivatization, when required. The extractives were also subjected to appropriate assays to establish the bioactivities. We have investigated over 60 medicinal plants and several microbial strains that have resulted in the isolation and characterization of 150 compounds, including 50 new molecules. The crude extractives A. paniculata, A. chinensis, S. sesban, M. oleifera, and S. cumini demonstrated statistically significant reduction of elevated blood glucose levels in alloxan/streptozotocin-induced diabetic rats. A total of 18 compounds were isolated and identified from these plants by extensive spectroscopic studies: Andrographolide, neoandrographolide, 14-deoxy-11,12-didehydroandrographoside, 6 α-hydroxystigmat-20(21)-en-3-one, and stigmasterol from A. paniculata; β-sitosterol, β-sitosterone, α-amyrin, 4 ' ,5-dihydroxy-7-methoxyflavone, and 2 α,3 β,19 α-trihydroxyolean-12-en-20-oicacid-3-O-β-D-galactopyranosyl-(1→3)-β-D-glucopyranoside from A. chinensis; 4 ' ,5-dihydroxy-6,7-dimethoxyflavone, 3,7-dihydrxyoleanolic acid, 7-methoxygenistein, and oleanolic acid-3-O-arabinoside from S. sesban; and 7-hydroxycalamenene, methyl-β-orsellinate , β-sitosterol, and oleanolic acid from S. cumini. The series of studies which we conducted in our laboratory have resulted in the isolation and characterization of numerous chemically unique and biologically interesting secondary metabolites from medicinal plants, microbes, and marine organisms. Some of these results are in conformity with the traditional and folkloric uses of the investigated plants.
Regulation of type 1 diabetes: the role of peroxisome proliferator-activated receptor gamma
Norazmi Mohd. Nor
School of Health Science, UniversitiSains Malaysia, Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia. E-mail: [email protected]
It is fairly well established that the pathogenesis of type 1 diabetes (T1D) is driven by type 1 cytokines and inhibited by type 2 cytokines. We have previously reported that IFNγ and IL-2 were increased, whereas IL-4 and IL-1 0 were decreased in the immune cells of the T1D model, non-obese diabetic (NOD) mice. We have also shown that the expression of peroxisome proliferator-activated receptor gamma (PPARγ), which has been implicated in immune regulation, was reduced in the peritoneal macrophages, CD4 + , and CD8 + lymphocytes of NOD mice. Recently, natural T regulatory cells (T-reg) and Th17 cells have been suggested to play roles in T1D. T-reg cells are thought to suppress T1D, whereas Th17 cells are believed to promote the disease, due to their plasticity to produce type 1 cytokines in vivo. PPARγ is reported to be a negative regulator of Th17 cell differentiation while the role of this receptor in T-reg cells is still unknown. We found that the level of PPARγ expression was significantly reduced in T-reg cells. Interestingly, PPARγ activation increased the Th17 cell differentiation in NOD mice but did not affect Th17 cell differentiation in the control, non-obese diabetic-resistant (NOR) mice. Our findings suggest that PPARγ plays some role in controlling T1D with the involvement of T-reg cells but was unable to dampen the differentiation of, probably committed, Th17 cells.
Occurrence of micro-albuminuria and the associated risk factors in type 2 diabetes mellitus patients at the time of diagnosis
R. Sivakanesan, J. P. Suraweera, V. L. U. Illangasekera
Department of Biochemistry, Faculty of Medicine, University of Peradeniya, Sri Lanka. E-mail: [email protected]
The world is facing an unprecedented epidemic of diabetes mellitus, especially type 2. An estimated 30 million people worldwide had diabetes in 1985. By 1995, this number had increased to 135 million. Now, World Health Organization predicts a rise to an alarming 300 million by 2025. Micro-albuminuria is a strong predictor of overt diabetic nephropathy and cardiovascular morbidity and mortality among type 2 diabetic patients. With respect to Sri Lankan diabetics, data on the occurrence of micro-albuminuria and the associated risk factors in type 2 diabetics, especially at the time of diagnosis are lacking. In our earlier study conducted at the Teaching Hospital, Peradeniya, Sri Lanka, we have observed the frequency of micro-albuminuria in diabetic patients to be 27% and it was significantly related to the duration of diabetes and hypertension. A hospital-based cross-sectional, descriptive and analytical study was carried out in three major hospitals in the district of Kandy. The sample studied (n = 268) represented newly diagnosed type 2 diabetic patients between 20 and 70 years of age. All the subjects were screened for diabetic retinopathy. Morning spot urine specimen collected from the subjects who refrained from strenuous physical activity or smoking. Microalbumin in urine was estimated by turbidimetric method using Randox kit. Blood samples were taken for assessment of lipid profile and fasting plasma glucose (FPG). Statistical analysis was done using SPSS 1 0.0, 1999 standard version. The subjects irrespective of gender were grouped into 1 0-year period interval. Out of the total samples, 67.2% are in the age group of 40-59 years, with more or less similar percentages for age groups of 40-49 and 50-59 years. Nearly, 15% of the study group comprised of elderly persons. The overall occurrence of micro-albuminuria in type 2 diabetic patients at the time of diagnosis was 25%. Out of 95 male subjects, 26 were micro-albuminuric, whereas out of 173 female subjects, 41 were micro-albuminuric. Therefore, the occurrence of micro-albuminuria among male subjects (27.4%) was higher than that of female subjects (23.7%). But the difference was not statistically significant (P = 0.507). The occurrence of micro-albuminuria among 20-39 years age category (18.0%) was more or less similar to that of 40-49 years age category (18.4%), whereas occurrence of micro-albuminuria among 50-59 years age category (33.0%) was more or less similar to that of 60-70 years age category (30.0%). Finally, the occurrence of micro-albuminuria among 50-70 years age category (63.0%) was higher than among 20-49 years age category (36.4%) and the difference in occurrence was marginally (P = 0.074) significant. However, age has an influence in the albuminuric status in the newly diagnosed type 2 diabetic patients. The significantly associated factors for micro-albuminuria were marital status (P = 0.013), hypertension (P ≤ 0.001), mean arterial pressure (P < 0.001), smoking (P = 0.012), and retinopathy (P < 0.001). With a borderline significance, advancing age (P = 0.074), location of hospital (P = 0.076), and FPG (P = 0.067) were associated with micro-albuminuria. In males, advancing age (P = 0.047), hypertension (P = 0.001), smoking (P = 0.014), and retinopathy (P < 0.001) were significantly associated with micro-albuminuria and a borderline significance was observed with mean arterial pressure (P = 0.069). The significantly associated factors for micro-albuminuria in females were location of hospital (P = 0.044), marital status (P = 0.002), hypertension (P < 0.001), mean arterial pressure (P = 0.001), retinopathy (P < 0.001), and FPG (P = 0.047). With a borderline significance, advancing age (P = 0.085) was associated with micro-albuminuria in females. The independent risk factors for micro-albuminuria in the subjects were hypertension (P < 0.001), retinopathy (P < 0.001), and marital status (P = 0.012). The independent risk factor for micro-albuminuria in males was retinopathy only (P = 0.004) and in females were hypertension (P = 0.006), retinopathy (P = 0.004), and marital status (P = 0.005). Compared to the entire study group and males, the occurrence of retinopathy as well as coexistence of retinopathy and micro-albuminuria was lower in females. The occurrence of micro-albuminuria among the subjects with high TC concentration (26.4%) was higher than that among the subjects with normal TC concentration (23.4%). But the difference was not statistically significant. Similarly, the occurrence of micro-albuminuria among the subjects with high FPG concentration (28.4%) was higher than that among the subjects with normal FPG concentration (17.9%). But the difference was not statistically significant. There was a significantly higher occurrence of micro-albuminuria in subjects with retinopathy (74.2%) than in subjects without retinopathy (18.6%). Only 11.6% of the subjects had only retinopathy, and 8.6% had both retinopathy and micro-albuminuria. The results thus indicate that in a noticeable number of newly diagnosed subjects, already the kidney and eye function have been affected due to diabetes. A considerable percentage (25%) of the type 2 diabetics is already prone to have micro-albuminuria at the time of diagnosis, whereas the males with retinopathy and the females with retinopathy and/or hypertension were observed to be at more risk of having micro-albuminuria at the time of diagnosis.
Kynurenine pathway is activated in diabetes
M. M. Essa 1,2 , M. Al-Maskari 3 , E. K. LIM 2 , M. I. Waly 1 , G. J. Guillemin 2 , S. Subash 1
1 Department of Food Science and Nutrition, Sultan Qaboos University, Sultanate of Oman, 2 Department of Pharmacology, Neuropharmacology group, University of New South Wales, Sydney, Australia, 3 Health Sciences, Al-Buraimi University, Oman. E-mail: [email protected]
The kynurenine pathway (KP) is the major route for tryptophan (TRP) catabolism. The intermediates generated in KP can be either neurotoxic, such as quinolinic acid (QUIN), or neuroprotective, such as picolinic acid (PIC), an important endogenous chelator. The KP activated during neuro-inflammation and oxidative stress conditions and serotonin is produced from TRP by serotonergic neurons. We hypothesize that KP might be involved in the pathogenesis of diabetes. This study aimed to characterize the expression of the KP in diabetic blood (serum) samples. Using high-performance liquid chromatography, we analyzed the levels of TRP and kynurenine, and with gas chromatography/mass spectrometry, the levels of PIC and QUIN, in the serum of diabetic patients and control subjects. Significantly altered KP metabolites were found in diabetic samples than controls. Our present results suggest that KP might be involved in the pathogenesis of diabetes and opened a new therapeutic door for diabetes.
Tualang honey: A potential anti-cancer agent
Nik Soriani Yaacob
Department of Chemical Pathology, School of Medical Sciences, UniversitiSains Malaysia, Health Campus, 1615 Kubang Kerian, Kelantan, Malaysia. E-mail: [email protected]
Tualang honey is rich in flavonoids and phenolic acids and has been shown to possess anti-microbial, free radical scavenging and anti-oxidant activities and wound healing properties. We observed that Tualang honey has significant anti-cancer activities against breast cancer cells in vitro. Accelerated apoptotic effects were observed when Tualang honey was used in combination with tamoxifen on MCF-7 and MDA-MB-231 cells, with involvement of caspase activation and modulation of expression of markers of apoptosis. Further analysis demonstrated that the anti-cancer mechanism involves changes in mitochondrial membrane potential and cell cycle arrest in the cancer cells. Interestingly, Tualang honey displayed chemopreventive ability on breast epithelial cell line, MCF-1 0A. The honey is not only non-cytotoxic to MCF-1 0A cells but is also capable of dampening the cytotoxic effect and DNA damage induced by tamoxifen on these epithelial cells probably via upregulation of repair proteins. Inhibition of DNA damage and expression of biomarkers of photocarcinogenesis following ultraviolet irradiation of mouse keratinocytes further demonstrates the chemopreventive potential of Tualang honey.
Against cancer? Why not nature!
Graduate Institute of Applied Science of Living, Tainan University of Technology, Biological Function of Dietary Phytochemicals, 529 - Jhongiheng Road, Yongkang District, Tainan City, 7 1 0 0 2, Taiwan. E-mail: [email protected]
Cancer metastasis refers to the spread of cancer cells from the primary neoplasm to distant sites, where secondary tumors are formed. From several decades ago to now, cancer lasts to be the leading-lethal cause worldwide and metastasis is yet the major cause of cancer-related death. The term of natural bioactives or phytochemicals is generally referred to the compounds exclusive of essential nutrients that have specific biological activity to human. For health benefits, the desire to use non-chemical therapy such as nutraceuticals supplementation to prevent pathology development is eager in the developing or developed countries. Numerous natural phytochemicals have been widely demonstrated to have the capability to prevent cancer metastasis. The in vitro and in vivo anti-invasive and anti-metastatic activities of phenolic acids, monophenol, polyphenol, and their derivatives (curcumin, resveratrol, gallic acid, chlorogenic acid, caffeic acid, carnosol, capsaicin, 6 -shogaol, and 6 -gingerol) as well as flavonoids and their derivatives (EGCG, EGC, ECG, EC, genistein/genistin, silibilin, quercetin, anthocyanin, luteolin, apigenin, myricetin, tangeretin, kaempferol, glycitein, licoricidin, daidzein, and naringenin) have been revealed. In addition, vast numbers of natural dietary compounds other than phenolics have also been demonstrated that they might also possess the capability to inhibit invasion and metastasis of various cancers. These non-phenolic compounds include terpenoids compounds (retinoids/retinoic acid, ursolic acid, ganoderic acid, ganodermanontriol, lucidenic acid, and zerumbone), isothiocyanates (sulforaphane, benzyl isothiocyanate, phenethylisothiocyanate, allylisothiocyanate, s-allycysteine, allicin, and diallyl disulfide), indole (indole-3-carbinol/3,3-diindolylmethane), carotenoids (lycopene/apo-8'- lycopenal, β-carotene, and lutein), alkaloids (caffeine and piperine), furcoumarins (bergamottin), lignin (sesamin), and xanthone (isoalavaxanthone). These lines of scientific evidence suggest that the daily consumption of natural foods containing adequate natural bioactives could be beneficial for the prevention of cancer metastasis or could improve cancer prognosis.
A novel combination immunotherapy for targeting murine breast cancer with interleukin-13 receptor alpha 2 DNA vaccine and an immunotoxin
Hideyiki Nakashima 1,2 , Syed. R. Husain 2 , Yuki Sato 1,2 , Mitomu Kioi 1,2 , Kenji Mitsudo 1 , Raj. K. Puri 2 , Iwai Tohnai 1
1 Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan, Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA. E-mail: [email protected]
Interleukin-13 receptor α2 chain (IL-13Rα2), a tumor-associated antigen, is a potential target for immunotherapy. A variety of human cancers express high levels of IL-13Rα2, but its precise role in tumor immunology is not known. IL13-pseudomonas exotoxin (PE), a targeted cytotoxin composed of IL-13 and mutated form of PE, induces specific killing of IL-13Rα2 positive tumor cells. In this study, we determined the efficacy of IL13-PE in combination with IL-13Rα2 DNA vaccination in murine 4T1 breast carcinoma, which naturally overexpress IL-13Rα2 antigen. For orthotopic 4T1 tumor model, cells were injected into the mammary fat pad in BALB/c mice. Mice receiving intra-tumoral injections of IL13-PE and subsequent DNA vaccinations reduced tumor size and significantly prolonged overall survival of animals compared to the control mice. Combination therapy caused higher CTL activity and interferon-γ release from splenocytes in vitro compared to the controls. Interestingly, mice which received combination therapy accumulated lower levels of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in spleen and tumors compared to the PBS-treated control mice. The mechanism of synergistic anti-tumor effect involved not only T-cell dependent tumor regression but also elimination of immunosuppressive elements, especially MDSCs and Tregs. A similar combination therapy will be applied in subcutaneous and orthotopic head and neck cancer models.
Interleukin-13 receptor α2 chain regulation in human head and neck by hyperthermia In vitro
Kei Sugiura 1 , Hideyuki Nakashima 1,2 , Makiko Okubo 1 , Itaru Sato 1 , Masaki. Iida 1 , Yuki Sato 1,2 , Mitomu Kioi 1,2 , Kenji Mitsudo 1 , Syed R. Husain 1,2 , Iwai Tohnai, Raj K. Puri 1,2
1 Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan, Tumor Vaccines and Biotechnology Branch, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda MD, USA. E-mail: [email protected]
Hyperthermia is often utilized together with chemotherapy and radiation as the increase in blood flow in tumor tissue results in increasing treatment efficacy. Interleukin-13-pseudomonas exotoxin (IL13-PE), a targeted cytotoxin composed of IL-13 and mutated Pseudomonas exotoxin, induces specific killing of IL-13 receptor α2 ( IL-13Rα2) positive tumor cells. Our objective is whether hyperthermia treatment of oral squamous cell carcinoma (OSCC) can modulate the expression of IL-13Rα2 and increase their sensitivity to IL13-PE, especially in IL13-PE-resistant cells. OSCC cell lines, HSC-3 and SCC-25 cells were heated to 43c for 1 h. The proliferation of heat-stressed OSCC cells showed >50% growth inhibition compared to control cells. Then, the expression levels of IL-13Rα2 and HSP70/HSP90 were analyzed. IL-13Rα2 was upregulated after heating of OSCC cells. Western Blot analysis of heat-stressed HSC-3 cells revealed that HSP70/HSP90 expression increased in time-dependent manner. Cytotoxic activity of IL13-PE was evaluated by protein synthesis inhibition assay. The assay with IL13-PE showed that heat-stressed OSCC cells decreased the number of IC50 compared to that of without heated OSCC cells. These data suggest that hyperthermia of human OSCC sensitize to IL13-PE most likely by upregulating the expression of cell-surface IL-13Rα2. Now, we are studying to observe the efficacy of IL13-PE after hyperthermia in a mouse model.
Oral submucous fibrosis: Pathogenesis and malignant transformation
W. M. Tilakaratne
Department of Oral Pathology, Faculty of Dental Sciences, University of Peradeniya, Sri Lanka. E-mail: [email protected]
High proportion of oral cancers in South Asia is preceded by some form of a pre-cancer. The recent changes to the terminology of pre-cancer paved the way for the new term, oral potentially malignant disorders (OPMD). The population prevalence of OPMD in Sri Lanka, based on one large epidemiological survey on the general population was estimated at 4.2%. One of our recent studies conducted using similar clinical criteria for detecting prevalence of oral pre-cancer showed a figure of 6.7%. Although there is a long list comprising of oral submucous fibrosis, leukoplakia, oral lichen planus, erythroplakia, chronic hyperplastic candidiasis, sideropenic dysphagia, tertiary syphilis, and actinic keratosis, the first two entities are the most important as a significant number of oral cancers arise from those in South Asia. Oral submucous fibrosis (OSF) was first described in the early 1950s, and it is a potentially malignant disease predominantly seen in people of Asian descent. The hallmark of the disease is submucosal fibrosis that affects most parts of the oral cavity, pharynx, and upper third of the esophagus. When the disease was first described in 1952, it was classified as an idiopathic disorder. The pre-cancerous nature of OSF was first described by Paymaster in 1956 when he observed slow growing squamous cell carcinoma in one-third of the patients with the disease. Although the disease was described in 1952, its pathogenesis and mechanisms of malignant transformation have been elusive. Exact mechanisms of imbalance in collagen metabolism leading to accumulation of fibrous tissue need to be understood in order to plan new treatment strategies. More importantly, carcinogenesis in the background of fibrosis has not been investigated adequately. However, our work together with research from other groups in the last two decades helped the clinicians and pathologists to understand the pathogenesis as well as malignant transformation to some extent. It is clear that the use of areca nut is the etiological factor for the deadly disease. The most important ingredient causing the disease appears to be arecoline present in areca nut. Further, areca nut is classified as a definite carcinogen by IARC. Therefore, health policy makers in South Asia should take this into consideration when planning health education programs as oral cancer is by far the commonest cancer in this part of the world. We have investigated the possible pathways of pathogenesis and malignant transformation in detail using basic as well as advanced molecular biological techniques. Most of the events that take place in pathogenesis and malignant transformation and their inter-relationships at various levels of the disease have been identified as a result of our work expanding over a period of 15 years on the subject of OSF.
Prognostic markers of oral squamous cell carcinoma
B. S. M. S. Siriwardena
Department of Oral Pathology, Faculty of Dental Sciences, University of Peradeniya, Sri Lanka. E-mail: [email protected]
Oral cancer synonymously defined as oral squamous cell carcinoma (OSCC) is among the 10 most frequent cancers globally and three quarters have been reported in the developing world. Further, oral cancer ranks as the third most common cancer after the stomach and cervix in developing countries. Unfortunately, in this part of the world where oral cancer is most common, information such as incidence, prevalence, mortality, treatment protocols, survival data, and prognostic indicators is least available. Oro-pharyngeal carcinoma is a major oncological problem in many regions of the world where tobacco habits are practiced in the form of chewing and/or smoking. Such habits are practiced by certain groups in Sri Lanka and other parts of south and south east Asia including India. Early diagnosis is the key to improve survival; thus, identification of these lesions at the stage of pre-cancer would certainly help in achieving better prognosis. Early diagnosis is found to be the single most significant factor in improving prognosis. Traditionally, histopathological parameters such as vascular invasion, metastasis, host immune response, etc., are considered prognostic markers for many cancers. For OSCC, we investigated less studied features such as pattern of invasion of the cancer. One of our early studies showed very convincing results on the relationship between pattern of invasion and metastasis, hence the prognosis. We have proven with several studies subsequently that the pattern of invasion is a very reliable factor in oral cancer to predict metastasis and it is being used in diagnostic histopathology reporting as a helpful guide for surgeons to plan the treatment for neck nodes in oral cancer patients. Another practical problem that we experience in the management of oral cancer in Sri Lanka and other south Asian countries is the presence of multiple single primaries or synchronous cancers which may be due to excessive exposure to carcinogens in the form of chewing habits. The prognosis and survival of synchronous cancers are notoriously less compared to single primary cancers. However, there were no studies comparing the two groups in order to analyze histopathological differences and to compare that with survival. In an attempt to identify molecules which may have an effect on predicting prognosis of oral cancer, several molecules were selected due to known biological properties of those molecules/genes in cancer biology. The molecules that we studied were Periostin, VEGF-C, Survivin, Matrix metallo-proteinases (MMP)-10, Aurora B, and HIF-1 alpha. HIF-1 alpha is a gene which we investigated in oral submucous fibrosis. As this was a novel finding in oral pre-cancer at that time, researchers started working on this in relation to oral cancer. Because of the consistency of results from different groups in predicting prognosis of oral cancer using this molecule, it can be considered a useful gene in metastasis and prognosis of oral cancer. The next molecule that we studied was periostin, a secreted protein, which has been suggested to function as a cell adhesion molecule for pre-osteoblast and to participate in osteoblast recruitment, attachment, and spreading. According to our study, this molecule shown to have a relationship with other metastasis associated histological features such as pattern of invasion which we showed previously. It was proved with our results that periostin has a strong relationship with angiogenesis, invasion, and metastasis. Therefore, identification of periostin in an incisional biopsy may help in predicting metastatic potential of the cancer. Survivin, another molecule that we studied belongs to the inhibitors of apoptosis gene family. It is well known that survivin overexpression is associated with a poor outcome in various cancers. In our study, we found that survivin overexpression in both nuclei and cytoplasm of HNSCC cells, and that both nuclear and cytoplasmic survivin overexpression were significantly associated with malignant behaviors of HNSCC including cell proliferation, differentiation, and lymph node metastasis. MMPs are a family of extracellular zinc-dependent neutral endopeptidases collectively capable to degrade extracellular matrix proteins. Degradation of ECM is an essential part of growth, invasion, and metastasis of malignant tumors. These results suggest that MMP-10 plays an important role for invasion and metastasis of OSCC, and therefore MMP-10 can be used as a marker for prediction of metastasis. Aurora-B kinase is a chromosomal passenger protein and is essential for chromosome segregation and cytokinesis. Aurora-B overexpression in various cancer cells induces chromosomal number instability to produce multi-nuclearity and relates to metastasis. Our group found that the labeling index of Aurora-B was significantly correlated with lymph node metastasis and histological grades of differentiation. The other molecule that we were interested was VEGF-C, angiogenesis-related gene. Angiogenesis is the most important requirement for the cancer cells to survive. Therefore, we hypothesized that VEGF-C expression is correlated with lymph vessel density, pattern of invasion, and metastasis. With a series of experiments we carried out, it was concluded that VEGF-C plays an important role for lymphangiogenesis and invasion in the metastatic process and can be a strong predicting factor for metastasis of oral cancer.
| Invited Lectures|| |
Anti-diabetic molecules from terrestrial plants and marine mangroves
Arvind K. Srivastava
Division of Biochemistry, CSIR-Central Drug Research Institute, Lucknow - 226 010, India. E-mail: [email protected]
In spite of phenomenal development in synthetic drug chemistry and antibiotics, plants still constitute an important part of pharmacopoeias in both the developed and developing countries. Plants were worshipped and regarded as more valuable than gold not only in India but also in other parts of the world where the modern civilization spread. This was mainly due to their magical power of providing relief to different ailments association with the creation of mankind. Uses of plants in India for health care date back to about 5000 years. In Ayurvedic or Indian system of medicine, crude drugs are obtained from plants and there are about 8000 herbal remedies for human ailments, besides the numerous plants used in folk medicine by tribal and rural people. Madhumeha which is presently known as diabetes mellitus is an age old anguish of the human beings since time immemorial. Nearly, 400 terrestrial plants including herbs have been described in the literature in the therapy or management of madhumeha. Today, chemical and pharmaceutical investigations on many of these have added a great deal of status to the use by the presence of active ingredients and their action in biological system. Bioactivity evaluation is an important part of development of new drugs from natural products at Central Drug Research Institute, Lucknow and in the anti-hyperglycemic activity evaluation program, the various parts of a large number of terrestrial plants and marine mangroves were screened and anti-diabetic activity in many of the terrestrial plants and marine mangrove have been confirmed in various animal models of type 2 diabetes mellitus. Further, chemical entities responsible for anti-diabetic activity in some of terrestrial plants such as Aegle marmelos, Ficus bengaliensis, F. racemosa, Pongamia pinnata, Trigonella foenum, Pterocarpus marsupium, Tectona grandis, Coccinia indica, Withania coagulens, Ocimum sanctum, Dodecedenia grandiflora, Cupressus semipervens, and marine mangroves, i.e., Xylocarpus granatum and Xylocarpus moluccensis were identified, their actions at molecular level are being explored. This investigation received financial supports from CSIR, New Delhi in the form of networked project-0032) and Ministry of Earth Sciences, New Delhi.
Anti-hyperlipidemic and beneficial role of Coumarin, naturally occurring flavonoids in experimental type 2 diabetes
Leelavinothan Pari, Narayanasamy Rajarajeswari
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainarar - 608 002, Tamil Nadu, India.
E-mail: [email protected]
Dyslipidemia is one of the most common complications of diabetes mellitus, significantly contributing to cardiovascular morbidity and mortality in diabetic patients. At present, dyslipidemia is most commonly treated with lipid-lowering drugs, some of which are associated with serious adverse side effects. The effects of dietary components on plasma lipid metabolism have recently received considerable attention, highlighting the importance of natural products as lipid metabolism regulators. Many medicinal plants have been found to be useful to successfully manage hyperlipidemia, these include Coumarin (1, 2-benzopyrone), a naturally occurring flavonoids from various plants including tonka beans, sweet clover, bilberry, green tea, and chicory. In this study, we examined a lipid-lowering effect along with anti-oxidant role of Coumarin in normal and experimental type 2 diabetic rats. Experimental type 2 diabetes mellitus was induced by a single intra-peritoneal injection of streptozotocin, 15 min after the intra-peritoneal administration of nicotinamide. Normal and type 2 diabetic rats were orally administered with 100 mg/kg body weight of Coumarin for 45 days. The results show that there were significant increases in tissue lipids, total serum cholesterol, triglyceride, and low-density lipoprotein cholesterol and a decrease in high-density lipoprotein cholesterol in experimental diabetic rats. Oxidative stress in diabetic rats were also indicated by increased levels of thiobarbituric acid reactive substances, hydroperoxides with decreased levels of superoxide dismutase, catalase, and glutathione peroxidase. Administration of Coumarin over a period of 45 days returned these levels to near normal. These results suggest that Coumarin has hypolipidemic along with anti-oxidant effects in type 2 diabetic rats.
Prevention of coronary artery disease and its complications in patients with diabetes mellitus
S. R. Gupta
Cardiologist, Tirupathi, India. E-mail: [email protected]
Diabetes mellitus (DM) is likely to affect 360 million people Worldwide by 2030. Cardiovascular disease (CVD) is the main cause of morbidity and mortality in persons with diabetes, most commonly due to coronary artery disease (CAD) followed by cerebrovascular disease and heart failure. Nearly, 80% of deaths in persons with diabetes are due to CVD. Diabetes poses 2-4-fold increase in risk of CAD and is considered CAD equivalent. Diabetes affects one out of three acute coronary syndrome patients (ACS) and associated with worse outcomes than non-diabetics. Diabetes nullifies protection enjoyed by young women from CAD. CAD occurs early in persons with diabetes and vascular changes may begin in pre-diabetic stage and have the potential for reversal if recognized early. Persons with DM often have greater number of risk factors for CAD-like systemic hypertension, dyslipidemia, obesity, and a pro-coagulent state. Clear association observed between severity of hyperglycemia and CVD risk. Endothelial dysfunction is the hall mark of diabetic vascular disease in the form of abnormal nitric acid function, increased endothelin and angiotensin 2, and decreased prostacyclin activity. Diabetic dyslipidemia is characterized by high triglyceride levels, low high-density lipoprotein (HDL), and increase in small low-density lipoprotein (LDL). Increased circulating tissue factors, factors V11, von wellibrand factor, and plasminogen activator inhibitor 1 and decrease in levels of anti-thrombin 3 and protein C are common in persons with DM and increase the thrombosis potential and atherosclerosis. Diabetes is also associated with increased oxidative stress with accumulation of advanced glycation products, lipid-rich plaque with inflammatory cells in filtration. Lifestyle interventions are the cornerstone of prevention of CAD and its complications in persons with DM as in non-diabetics. Cessation of smoking, moderate aerobic exercise, diet modification, and weight control are strongly recommended by ADA and AHA. Number of pharmacological strategies is proven effective in persons with diabetes like intensive lowering of hypertension and lipids. ACE inhibitors are to be considered in diabetes independent of HTN and are drugs of choice in patients of diabetes with HTN or other CAD risk factor. About 70% of diabetic patients develop HTN and require to be treated more aggressively and the target BP is <130/80 mm of Hg. ARBs to be considered when ACE inhibitors are not tolerated. Beta-blockers which were relatively contraindicated, in recent meta-analysis of outcome trials showed benefit in patients with DM in ambulatory setting and post-ACS patients. Reduction of LDL is the prime target in management of diabetic dyslipidemia. Statins are recommended for all patients with DM older than 40 years with one or more CAD risk factors or younger in the setting of CAD or multiple risk factors. The target for LDL is <70 mg/dl. The next targets are triglycerides and non-HDL cholesterol which may require increase in statin dose or addition of nacin, ezitamide, fish oils, or fibrates. ADA and AHA recommend Aspirin 75-162 mg for all patients with DM who have CAD or men more than 50 years and women over 60 years with additional risk factors. Incremental benefit observed with addition of clopidogrel. Accumulated data about the effectiveness of glucose control on CVD reduction are less robust. Recent major trials showed more intense glucose control which showed no significant CVD benefit than usual control. Target glucose control in DM is A1C <7%. Metformin is found to be the main therapeutic agent in all diabetic patients without contraindications to it. Combination therapy including insulin to achieve A1C targets may be required. The approach to ACS patients with DM is similar to general population with target glucose levels <180 mg/dl. Intensive anti-platelet therapy is beneficial particularly, Tirofiban and Eptifibatids showing significant mortality benefit than non-diabetics. Diabetics derive more benefit with primary reperfusion and angioplasty and higher restenosis and worse long-term outcome common. CAD, both chronic and acute remains common cause of heart failure in diabetes. ACE inhibitors are the first choice. Eplerenone is recommended in all patients of DM with decreased ejection fraction. Beta-blockers are also effective, particularly carvidolol which has favorable effect on insulin sensitivity and plasma lipids. Thus, persons with diabetes are at high risk of CAD and its complications. Lifestyle changes, aggressive management of the associated risk factors like systemic HTN, dyslipidemia, use of anti-platelet drugs, and better control of hyperglycemia help in prevention of CAD and reduce its morbidity and mortality in persons with diabetes as in non-diabetic population.
Trends in diabetes research
K. V. Pugalendi
Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, India. E-mail: [email protected]
Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia (increased blood glucose) resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nerves, heart, and blood vessels. According to World Health Organization, by 2030, more than 75% of people with diabetes will be from India. The underlying goal of all diabetes treatment and management is to maintain an adequate blood glucose concentration. Due to unwanted side effects of available oral hypoglycemic drugs (insulin secretagogues, biguanides, thiazolidinediones, α-glucosidase inhibitors, and intestinal dipeptidyl peptidase four inhibitors), the efficacies of these compounds are debatable and there is a demand for new compounds for the treatment of diabetes. Nowadays, insulin pen, jet injector, insulin inhalers, insulin pump, and insulin pill are used to treat type 1 diabetes mellitus. Vaccine has been developed, which stops the destruction of pancreatic beta-cells in humans, thereby preventing type 1 diabetes in people at high risk and also halting its progress in people newly diagnosed with it. In people with type 1 diabetes, the islet cells in the pancreas no longer produce insulin and so transplanting a new pancreas to a person with type 1 diabetes would cure their disease. A gene called SHIP2 which appears to regulate insulin is a potential gene therapy target for the treatment of type 2 diabetes. The most widely used insulin-secreting cell lines are RIN, HIT, MIN, INS-1, and TC cells, which produce insulin and small amounts of glucagon and somatostatin. Studies on animal models of diabetes have contributed greatly in understanding the etiology and pathogenesis of the disease. It also helps in the development and evaluation of newer agents for the treatment of diabetes. Diabetes research is the only way that is going to help us to find a cure in the future. Diabetes is a common disease where every individual needs unique care. Management of diabetes without any side effects is still a challenge for the medical system. Hence, search for a drug with low cost, more potential, and without adverse effects is being pursued in several laboratories around the world. People with diabetes and their families must be aware of the latest medical therapies and approaches, as well as healthy lifestyle choices. Screening for diabetes and creating awareness among common man regarding diabetes is indeed a great service.
Design, synthesis, characterization, and evaluation of anti-diabetic activity of novel vanadium and zinc complexes for the treatment of experimental diabetes
Department of Biochemistry, University of Madras, Guindy Campus, Chennai - 600 025, India. E-mail: [email protected]
The use of metals in therapeutic drugs becomes increasingly important over the last couple of decades, resulting in a variety of exciting and valuable metallo-pharmaceutical drugs. Zinc and vanadium are the two biologically important elements known to possess anti-diabetic properties. The development of zinc and vanadium complexes with various ligands in order to reduce the toxicity of the metals continues. In this study, an attempt has been made to synthesize zinc and vanadium complexes using flavonol as a ligand. The complexes were subjected to spectral characterization. Acute and chronic toxicity studies revealed the non-toxic nature of the complexes. Oral administration of the complexes at a concentration of 5 mg/kg b.w./rat/day for 30 days to streptozotocin-induced diabetic rats showed significant reduction in blood glucose, glycosylated hemoglobin (HbA1c), with concomitant improvement in plasma insulin levels. Further, the oral glucose tolerance test performed in experimental rats indicated that the zinc and vanadium complexes have significant anti-hyperglycemic activity in streptozotocin-induced diabetic rats. The extent of oxidative stress in experimental diabetes was assessed by determining lipid peroxide levels, pancreatic tissue anti-oxidant enzyme activities, and plasma concentrations of non-enzymatic anti-oxidants. Oral treatment with the zinc-flavonol as well as vanadium flavonol complex significantly improved anti-oxidant levels and alleviated levels of oxidative stress markers. Histological observations revealed that complexes effectively protect pancreatic β-cells against oxidative damage. The results of this study indicate that the zinc and vanadium flavonol complexes possess anti-oxidant activity in addition to its anti-hyperglycemic nature.
Diabetes and cancer: Common disease-biology insights and compelling need for a "diabetoncology" approach
Madras Diabetes Research Foundation, Chennai - 600 086, India. E-mail: [email protected]
A growing body of evidence indicates a strong association between type 2 diabetes and cancer. The biological nature of this association, however, is not clearly understood. Epidemiological data suggest that patients with diabetes have a higher risk of developing several types of cancer, including liver, pancreatic, colorectal, gynecologic, and breast cancer. Cancer prognosis has also been suggested to be adversely affected by diabetes. The three most obvious means by which diabetes could influence the development and spread of cancer are insulin, blood glucose, and inflammation. Although hyperinsulinemia with stimulation of IGF-1 axis stimulates the proliferation of certain cancer cells by mechanisms that utilize both the phosphatidylinositol-3 kinase and MAP kinase/Akt signaling pathways, it is also a cell survival (anti-apoptotic) mechanism that enhances tumor cell migration and invasive capacity. Though insulin is the main suspect, researchers are also exploring whether high blood glucose may contribute to cancer because one trait of cancer cells is that they are adept at absorbing glucose from the blood with no need for insulin. Thirdly, inflammation is most important underlying issue both in diabetes and cancer. In order to understand the "bigger scientific picture," there is an imperative need to address the following questions: (a) Is there a meaningful association between diabetes and cancer incidence or prognosis? (b) What risk factors are common to both cancer and diabetes? (c) What are the possible biological links between diabetes and cancer risk? Diabetes treatments influence cancer risk or cancer prognosis? Several recent studies emphasize that treatment of diabetes and insulin resistance with dietary interventions, increased physical activity, and insulin-lowering drugs, such as metformin, may improve prognosis and responsiveness to anti-cancer treatments in patients with diabetes and cancer. In the era of treatment selectivity and molecular-targeted anti-cancer drugs, the accumulating evidence of common pathways linking cancer and diabetes is increasingly pointing the way forward for novel therapeutic avenues. Irrespective of their domain, researchers studying the molecular pathogenesis of diabetes and cancer should foster collaborations on a common cell-biology/disease-biology platform. The time has also come to overcome the conventional tunnel vision that results in two diseases being treated by separate clinicians, and to move toward a comprehensive approach that is ideally treated by future "diabetoncologists."
Recent trends in the treatment of cancer and diabetes
Shiradi Sai Trust and Hospital, Nammakal, India.
E-mail: [email protected]
Recent trends in the treatment of diabetes and cancer are discussed in this paper. Research studies of Swetia Chirayata leaves and Trigonella seeds prove their anti-hyperglycemic activity for diabetes. Combined suspension of extract of Swertia Chirayata and Trigonella Foenum graecum showed minimum blood glucose level. Reliable researches in the last few years showed that phytochemicals are effective in the treatment of cancer. These agents have been shown to suppress cancer cell proliferation and inhibit activation pathways. These chemopreventive agents reverse chemoresistance and radioresistance in cancer patients. These results suggest that the hypoglycemic action is mediated by the activation of an insulin signaling pathway in adipocytes and liver cells. In recent years, there are many reports of anti-cancer activities of artemisinins. Artemisinins have inhibitory effects on cancer cell growth, including many drug- and radiation-resistant cancer cell lines. Motivated by these studies, the author himself undertook original clinical trials with two herbal compounds Mithru Sirusti, (for cancer) and Kanaya Sirusti (for diabetes). A trial with 72 cancer patients and 82 diabetic patients has given excellent results. Dramatic drop in blood glucose for diabetic patients was recorded and all cancer patients showed excellent recovery. The immunity boosting mechanism is to be studied further. Paper discusses the recent developments in the treatment of cancer and diabetes, gives valuable insight and methodology of the researcher's own treatment model of both illnesses with confirmatory laboratory findings. Researcher concludes that herbal medicines have excellent scope in the treatment of cancer and diabetes and also that researchers should exchange their data and findings to get herbal medicines their rightful place in the treatment of chronic diseases.
Development and characterization of Interleukin-4-targeted immunotherapy for cancer
Prabhudas S. Patel
Biochemistry Research Division and Cell Biology Division, The Gujarat Cancer and Research Institute, Ahmedabad - 380 016, India. E-mail: [email protected]
Identification of over-expressed cell surface receptors is critical for development of cancer vaccines and targeted therapies. It has been demonstrated that a variety of human tumors and tumor cell lines overexpress IL-4 receptors. The receptor-targeted anti-cancer approach was developed by constructing a chimeric fusion protein that consisted of IL-4 and BAD gene to produce cpIL-4BADaa immunotoxin. This immunotoxin binds to receptor positive tumor cells specifically, blocking protein synthesis and killing them. The in vitro testing of this immunotoxin was carried out on glioblastoma cell lines and head and neck cancer cell lines. For in vitro analysis, cell viability and colony-forming assays were performed and IC 50 was calculated. In vivo testing was also performed on BALB/c mice. For in vivo analysis, the toxin was given through intra-tumor, intra-peritoneal, and intra-venous routes. In vitro and in vivo proved anti-cancer properties of the immunotoxin. The results suggested that this immunotoxin may serve as targeted therapy for treating human cancers.
Effect of Triphala mouth rinse on human oral cancer cell lines: An In vitro analysis
P. D. Madan Kumar
Department of Public Health Dentistry, Ragas Dental College and Hospital, Chennai - 600 119, India. E-mail: [email protected]
According to the World Health Report 2004, cancer accounted for 7.1 million deaths in 2003 and it is estimated that the overall number of new cases will rise by 50% in the next 20 years. In India, the age standardized incidence rate of oral cancer is 12.6 per 100,000 population. Patients with cancer in the head and neck area can be treated with surgery, radiotherapy, or a combination of both. A well-known side effect of radiation is mucositis. Hence, use of the mouth rinse becomes inevitable during the treatment of oral cancer. Though traditionally allopathic preparations have been used in patients with oral cancer for maintenance of oral health and reduce the incidence of treatment-induced oral mucositis, recent studies have shown the effectiveness of traditional Indian Ayurvedic preparations on oral health. Among them Triphala, a tradition Ayurvedic preparation prepared by mixing three components of an herbal plant has been found to be effective against periodontal diseases and dental caries. This study focuses on the effectiveness of Triphala mouth rinse on human oral cancer cell lines and the assess whether it exerts any cytotoxic effect on the human oral cancer cell lines. If found to be effective against oral cancer cell lines, Triphala can be used as a cost-effective therapeutic and preventive regimen for patients with oral cancers.
Animal models in experimental oral cancer and their management
K. Vasudevan, S. Manoharan 1
Departments of Zoology, and 1 Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar - 6 08 002, Tamilnadu, India. E-mail: [email protected]
Oral cancers are the world's most common human neoplasm and account for 3% of all newly diagnosed cancer cases. Biologically and clinically relevant animal models are essential to study multiple stages of oral carcinogenesis including normal tissues, aiming for the development of diagnostic and prognostic markers. A number of chemical carcinogens such as coal tar, 20-methylcholanthrene, 9,10-dimethyl-1,2 benzanthracene, and 4-nitroquinoline-1-oxide have been used in experimental oral carcinogensis. The several rodent models used for in vivo evaluation for oral cancer employ known carcinogens, transplantation, and genetic (knockout and transgenic) induction methods. These models are described together with their advantages and disadvantages. Their optimization and application in future research may improve the early detection and treatment of oral cancer. Experimental animal models care and management of treatment groups with reference to rodents will be discussed.
Attenuation of hepatocellular carcinoma by melatonin or α-ketoglutarate is associated with modulation of 24-h rhythms of oxidative stress and anti-oxidant status in rats
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram - 608 002, Tamil Nadu, India. E-mail: [email protected]
Tumors and tumor-bearing hosts exhibit markedly distorted rhythms which can serve as markers in early diagnosis and prognosis of cancer. Chronotherapy (administration of drugs at their best tolerated time) would enhance the efficacy and decrease the toxicity of anti-cancer drugs. Melatonin and α-ketoglutarate (α-KG) act as inhibitors of tumor promoting effect of N-nitrosodiethylamine (NDEA). Wistar rats received (20 mg/kg b.w.) of NDEA for 20 days. Melatonin (5 mg/kg b.w.) or α-KG (200 mg/kg b.w.) was given on a daily basis for 20 weeks. At the end of 20-week period, blood samples were collected from the tail at six time points during a 24-h period and the rats were sacrificed, the liver being macroscopically inspected. As markers for liver function, the activity of aspartate transaminase (AST) and alanine transaminase (ALT) and the levels of α-fetoprotein (α-FP) were measured in serum. To assess lipid peroxidation and the anti-oxidant status in blood, plasma levels of thiobarbituric acid reactive substances (TBARS) and of reduced glutathione (GSH) were measured, together with the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) in the erythrocyte fraction. Macroscopically, detectable hepatic tumors developed in all NDEA rats, an effect prevented by melatonin or α-KG. NDEA administration augmented significantly mesor and amplitude of 24-h rhythm of AST (211.3 and 5.7), ALT (117.8 and 8), αFP (8.9 and 1.3), and TBARS (4.7 and 0.2) levels and decreased mesor values of 24-h rhythm of GSH concentration and SOD (1.5), CAT (2.9), GPx (14.8), and GST (2.0) activities. Acrophases were delayed by NDEA treatment in all cases except for that of αFP which became phase-advanced. Co-administration of melatonin or α-KG partially counteracted all effects of NDEA. Melatonin administration decreased mesor of TBARS (2.1) significantly and augmented mesor of SOD (4.2) activity as compared to control. The results indicate that melatonin and α-KG are effective in protecting the circadian sequels of NDEA administration and the melatonin augmented the anti-oxidant defense in rats.
Diabetes and cancer: An analysis of 5 years of publications (2008-2012) with special reference to India
B. Bhat, M. Pathak, L. Ramamani, S. Burde, R. S. Jayasomu
CSIR-National Institute of Science Communication and Information Resources (NISCAIR), New Delhi, India. E-mail: [email protected]
Publications on diabetes and cancer in last 5 years (2008-2012) were analyzed using common searching tools viz., scopus, web of knowledge, and Google scholar. All the three sources were searched for number of records on three categories: "Diabetes and Cancer," "Diabetes," and "Cancer," independently for worldwide (author's affiliation anywhere in the world) as well as for India (from India) for the period 2008-2012. Google scholar which is more generic gave maximum number of hits (records) with 526,000, 756,000, and 596,000 for each category in worldwide search and 19,800, 36,100, and 80,400 hits specific to India. Although scopus showed 12,058, 151,959, and 508,467 hits for respective categories of search worldwide and 464, 6163 and 11,944 for India, ISI Thomson's web of knowledge gave a very conservative figure of 6792, 106,089, and 375,743 for records across the globe and 171, 2815, and 7590 for India. Year-wise data have shown an increasing trend in number of publications on diabetes and cancer independently from 2008 to 2011 but showed a decline during 2012, whereas publications on "diabetes and cancer" combined have shown a consistently increasing trend from 2008 to 2012. In fact, it showed a quantum jump from 2011 to 2012, possibly indicating the researchers' interest in exploring the association between the two life-threatening diseases that rank 12 th and 2 nd leading cause of death, respectively. Details such as top 10 authors who publish more; organizations, countries, and the sources (journals) among top 10; and whose works are most cited, etc., under each category for both worldwide and India have been worked out.
CSIR-NISCAIR, a premier institute in science publishing in India for last six decades has published 418 and 592 peer-reviewed papers on diabetes and cancer during this period. While Indian Journal of Experimental Biology carried the most number of articles both in diabetes (134) and cancer (167), Indian Journal of Natural Products and Resources published 67 papers on diabetes followed by Indian Journal of Biochemistry and Biophysics (IJBB) with 52 papers. IJBB published 82 papers on cancer followed by Indian Journal of Chemistry section B which published 69 papers. Among the IJBB papers under "diabetes," "anti-diabetic and anti-oxidant potential of ethanolic extract of butea monosperma leaves in alloxan-induced diabetic mice" by Sharma and Garg published in 2009 received maximum citations (24 times), the paper, "effect of curcumin and ferulic acid on modulation of expression pattern of p53 and bcl-2 proteins in 7,12-dimethylbenz[a] anthracene-induced hamster buccal pouch" by Balakrishnan et al., published in 2010 received maximum citations (8 times) under cancer category.
The rosy lips that lost the luster…. why?
S. K. Hayath Basha
Department of Biochemistry, Islamiah College, Vaniyambadi - 635 752, Tamil Nadu, India. E-mail: [email protected]
Love is a magic thread that binds every human being into one. When a man is born as a child, his rosy mouth expresses "maa," the first and foremost lovable word in the world. This rosy lovely mouth has lost its luster by his bad habits of utilizing tobacco and alcohol in various ways. At last, these habits become the cause of a cruel disease called oral cancer. 75% of all oral cancers are due to heavy alcohol and tobacco consumption. Both alcohol and tobacco temporarily stimulate (speed-up) nerves and body. The people once practiced to these bad habits, become addicted for seeking the temporary pleasures to forget their worries and problems they face in everyday life. Almost all the types of oral cancer could be prevented by the healthy habits, treated, or even cured in early diagnosis. This paper throws light on the various risk factors and preventive measures of oral cancer.
Designing of antagonists to anti-apoptotic members of Bcl-2 family proteins using peptidodynmimetic method
Department of Bioinformatics, Structural Biology Lab, School of Chemical and Biotechnology, SASTRA University, Thanjavur - 613 401, Tamil Nadu, India. E-mail: [email protected]
Bcl-B, one of the six anti-apoptotic proteins identified so far, interacts specifically with pro-apoptotic protein Bax implying that the Bcl-B must play an important role in the apoptotic process exclusively mediated by the Bax. Hence, it is indispensable of designing specific inhibitors to the Bcl-B in order to avoid adverse effect on the chemotherapy treatments of specific cancers overproducing the anti-apoptotic protein. In the present studies, BH3-mimetics that are capable of displacing BaxBH3 from Bcl-B have been screened using "peptidomimetic" and "peptidodynmimetic" methods. Pharmacophore patterns representing essential residues of hBaxBH3 to interact with hBclB were identified under static (peptidomimetic method) and dynamic (peptidodynmimetic method) conditions. The patterns were then used to collect small molecules mimicking the peptide interactions with the protein and the collected chemical compounds have been named as "peptidomimetics" and "peptidodynmimetics" in the former and later methods, respectively. Strikingly, the "peptidodynmimetics" showed superior qualities to the "peptidomimetics" in terms of ligand efficiencies, bioavailability, and pharmacokinetics for interacting with the hBclB as analyzed by means of dockings, molecular dynamics, and pharmacokinetic prediction software tools. The experimental validations for a few numbers of the "peptidodynmimetics" identified from the studies are right now under progress. The unique advantages of the "peptidodynmimetic method" to screen/identify highly efficient BH3-mimetics to modulate other anti-apoptotic proteins-BH3-only peptides interfaces that are, in general, composed of a heap of amino acids have also been discussed in detail.
Strategy in drug delivery system
Medicinal Chemistry and Nanoscience Research Laboratory, Centre for Research and Development, East Campus, PRIST University, Thanjavur - 614 904, Tamilnadu, India. E-mail: [email protected]
Poor water soluble compounds are major problem for drug formulation and it was difficult to use them by conventional formulation techniques that abandoned many drugs on early days of herbal research. The medicinal plants identified by many indigenous system of India such as Ayurvedha and Siddha have used their own knowledge in the formulation process which is still unclear but they are effective and being practiced all over India. The modern researchers just consider the benefits suggested by these indigenous systems and take lightly the concept of formulation process followed by the indigenous system. Probably this was the reason for abandoned drugs. Nowadays, modern science has developed many instruments and technologies that solve all the problems of solubility. This paper discusses the systematic and most accepted strategies in the formulation technology. This will help the researches to minimize the dose and toxicity. The improvement of efficacy, target delivery, and best bioavailability are the prime factors of therapeutic action that can be achieved by this approach. This also will help the manufacturer to prepare stable drugs for the convenient transportation and storage.
| Oral Presentations|| |
Tread mill test and hsCRP in diabetics: A correlation study
Deepa S. Sajjanar
Department of Biochemistry, Blde S Shri B. M. Patil S Medical College, Bijapur, India
The levels of hsCRP as well as exercise tread mill test responses have been used for assessing prognosis in individuals without overt heart disease. The exercise testing responses alone cannot be used for the prognosis, whereas hsCRP is a recommended predictive marker for cardiovascular disease risk even in diabetics. This study was done to evaluate the correlation between hsCRP levels and exercise tread mill test responses. Around 40 diabetics were enrolled in the study, serum hsCRP and exercise tread mill test variables such as exercise time, maximum heart rate achieved, and heart rate recovery at 1 st and 3 rd min were evaluated in each of the patients. HsCRP levels (mg/L) and the exercise time in seconds were negatively correlated in both men and women and were statistically significant (P value < 0.001). This study concluded that increased hsCRP levels were associated with unfavorable exercise capacity in both sexes. These findings suggest that inflammatory status may play a role on tread mill exercise test responses in diabetics without overt heart diseases.
Usefulness of estimation of non-high-density lipoprotein cholesterol in type 2 diabetes
Nilima Dongre, S. S. Walvekar, J. G. Ambekar, Rama Jailkhani
Department of Biochemistry, BLDEU's Shri B. M. Patil Medical College, Bijapur - 586 103, India
It has been suggested that non-high-density lipoprotein (non-HDL) cholesterol measure is a useful evaluation tool to assess heart disease death risk. The non-HDL cholesterol is defined as the value between total cholesterol and HDL-total cholesterol, and it involves the different fractions of lipoproteins: Low-density lipoprotein (LDL), intermediate-density lipoprotein, and very LDL, including highly atherogenic lipoproteins as very LDL remnants. The elevated coronary heart disease (CHD) risk affecting patients with type 2 diabetes may be attributed to a combined dyslipidemia. The purpose of this study was to compare the values of non-HDL cholesterol as a cardiovascular risk marker in diabetic with CHD and non-diabetic with CHD. It was found that the mean values of non-HDL cholesterol in the diabetic and CHD groups were higher than the values from the control group. Non-HDL cholesterol is found to be a quick and simple way to estimate the risk of developing cardiovascular disease. This study concludes though the results, show the significant increase in non-HDL cholesterol levels; to predict it to be a marker for CHD large data must be studied. Patients' follow-up is important to see the glycemic status by measuring the HbA1c. Further study needs to be carried out to assess the predictive value of non-HDL cholesterol verifying its specificity and sensitivity.
Modulation of reverse cholesterol transport by Butea monosperma bark extract in streptozotocin-induced diabetic rats
B. T. Divya, S. Mini
Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala, India
Diabetes is associated with profound alterations in the plasma lipid and lipoprotein profile with an increased risk of cardiovascular disease (CVD). CVD is the major cause of morbidity and mortality in both type 1 and type 2 diabetes. The availability of multiple lipid-lowering drugs and supplements provides new opportunities for patients to regulate lipid levels. In this study, we evaluated the effect of Butea monosperma bark extract (BMBE) in diabetes-induced dyslipidemia. Effects of ethanolic extract of BMBE (500 mg/kg b.w.) on the levels of serum glucose, cholesterol, triglycerides, high-density lipoprotein (HDL), apo A1, apo B, plasma insulin, and LPL were studied in streptozotocin (40 mg/kg bw, i.p.)-induced diabetic rats. It was found that BMBE treatment for 45 days significantly reduced the serum glucose, TC, TG, and apo B in diabetic rats. At the same time, markedly increased plasma insulin, LPL activity, serum HDL, and apo A1 were found in BMBE-treated diabetic rats. Expression of ABCA1 and ABCG1 was examined in the liver of experimental rats. Significant increase in the expression of ABCA1 and ABCG1 was observed in liver of diabetic rats receiving BMBE treatment as compared with the diabetic group. The findings from both in vivo and molecular studies reveal the hypolipidemic potential of BMBE and suggest that the plant extract may be useful for the management of diabetic dyslipidemia.
Study of adenosine deaminase, insulin resistance, and inflammation in gestational diabetes mellitus and normal pregnancy
C. Selvakumar, R. Kalaivani
Department of Biochemistry, Meenakshi Medical College and Research Institute, Enathur, Kanchipuram - 631 552, Tamilnadu, India
The aim of this study was to investigate the level of ADA activity, insulin resistance, and inflammation in normal pregnancy, GDM, and normal non-pregnant women. The plasma catalytic concentration of ADA, fasting insulin, fasting glucose, and IL- 6 was measured in samples of 30 GDM, 30 normal pregnant, and 30 non-pregnant healthy women. Adenosine deaminase activity was significantly higher in GDM (27.50 ± 7.04 IU/L) and pregnant women (22.69 ± 8.26 IU/L) than those of normal non-pregnant individuals (14.05 ± 3.11 IU/L) (P < 0.0001), but the ADA level was not significantly different from GDM and normal pregnant women (P = 0.95). There were significant differences between IL- 6 levels in GDM and pregnant women. Insulin resistance was seen in GDM. Adenosine deaminase activity was significantly higher in GDM and pregnant individuals than normal group in this study. Our study hypothesizes that increased ADA activity and IL- 6 may be due to altered immunity.
Angiotensin-converting enzyme gene insertion/deletion polymorphism and microalbuminuria in type 2 diabetes mellitus in South Indian population
K. Ramalingam, J. N. Naidu, Dasu 1
Departments of Biochemistry, and 1 General Medicine, Narayana Medical College, Nellore - 524 003, Andhra Pradesh, India
The insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been shown to be associated with a number of complications of type 2 diabetes. Results on the development and progression of albuminuria, however, have remained controversial, with ethnic differences being a potential reason. This study aimed to demonstrate the relationship between ACE genotype and progression of micro-albuminuria in South Indian patients. One-hundred and fifty patients with type 2 diabetes were categorized in this cross-sectional study into following groups: Normoalbuminuria (n0 = 55), micro-albuminuria (n = 50), and macro-albuminuria (n = 45). ACE gene I/D polymorphism genotypes were determined using the polymerase chain reaction method. The distribution of ACE genotypes was significantly different among the groups (P < 0.001), with the II genotype decreasing and the DD genotype increasing in frequency with increasing severity of albuminuria. Multivariate regression analysis showed that the ACE genotype did not change the odds of having micro-albuminuria versus normoalbuminuria, whereas the D allele independently increased the odds of having macro-albuminuria versus micro-albuminuria approximately 3-fold (P < 0.01). In south Indian patients with type 2 diabetes, the D allele is associated with progression, but not development of albuminuria.
Detection of SNPs in slc22a1 gene in type 2 diabetes mellitus patients undergoing metformin drug therapy
V. K. Prasannaswaamy, N. Manoj Kumar
Department of Genetic Engineering, SRM University, Chennai, India
Personalized medicine is the concept that drug therapy can be tailored to a person's genetic make-up. Personalized medicine has its origins in pharmacogenetics, where the genetic variations of human individuals can guide the selection of drugs, in order to maximize useful effects and to minimize harmful side effects. The application of personalized medicine allows for an earlier detection and a more effective treatment of many chronic diseases such as diabetes, cancer, etc. Diabetes mellitus, or simply diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced. Metformin, a drug belonging to the biguanide class, has become the first line of defense against type 2 diabetes mellitus (T2DM). The major action of metformin is exerted in the liver, where it reduces the glucagon-mediated glucose output by the liver. Metformin is able to exert glucose-lowering actions with a low risk of hypoglycemia, as well as reduce the likelihood of developing macrovascular (hypertension and atherosclerosis) and microvascular (neuropathy, retinopathy, and nephropathy) complications, these qualities make it an attractive first-line therapy. However, metformin results in adverse events such as diarrhea and nausea that occur in about 30% of patients, or a more serious but very rare side effect, lactic acidosis. Despite an exceptional efficacy and safety profile, several T2DM (about 38%) still fail to reach glycemic goals in metformin therapy. The inter-patient variability in response to metformin therapy is found to be related to polymorphisms in the organic cation transporter (OCT) genes and the multidrug and toxin extrusion (MATE) genes. SLC22A1 and SLC22A2 are the genes which code for OCT1 and OCT2, respectively, whereas SLC47A1 and SLC47A2 genes encode for the MATE1 and MATE2-K proteins. In this study, the SNPs in SLC22A1 genes will be detected in T2DM patients undergoing Metformin therapy.
Herbal treatment for diabetes and cancer
V. Sangeetha, P. S. Sharavanan 1
Departments of Botany, Govt. Thirumagal Mills College, Gudiyattam, 1 Annamalai University, Annanmalai Nagar - 608 002, India
Traditional medicinal plants are gifted by god into the world. These herbals are used for the treatment of cancer and diabetes. The use of Ayurvedic medicines is common in the world. It has been estimated that almost 75% of the world's population have therapeutic experience with herbal remedies. The herbal plants Azadirahta indica, Ocimum sanctum, and Emblica officinalis have anti-pyretic, anti-cancer, anti-diabetic, anti-oxidant, and analgesic properties. A number of clinical studies have been carried out in recent years that show potential link between herbal therapies and improved blood glucose control in diabetic subjects. This study discusses about the use of anti-cancer and anti-diabetic medicinal plants.
Confirmation of traditional claims of anti-hyperglycemic activity in selected edible and medicinal plants
Savita Pal, Rakesh Maurya 1 , Akhilesh K. Tamrkar, Arvind K. Srivastava
Divisions of Biochemistry and 1 Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow - 226 001, India
The crude powders as well as ethanolic, aqueous ethanolic (50%), and aqueous extracts of the parts of edible plants, i.e., Allium sativum, Allium cepa, Aloe vera, Bauhinia forficata, Ipomea batatas, and Mangifera indica and medicinal plants, i.e., Catharanthus roseus, Caesalpinia bonducella, Eucalyptus globulus, Ficus bengalensis, Phyllanthus niruri, Potentilla fulgens, Tinospora crispa, and Terminalia arjuna were evaluated for their respective hypoglycemic and anti-hyperglycemic effects on normal and streptozotocin (STZ)-induced diabetic rats with and without sucrose challenge. No significant effect of either the crude powder or any of the extracts on blood glucose profile of normal rats was found, whereas the crude powders and ethanolic, aqueous ethanolic, and aqueous extracts of many of these plants showed improvement on glucose tolerance in both normal and STZ-induced diabetic rats post-sucrose load. Crude powders as well as the said extracts were found efficient in lowering blood glucose profile of STZ-induced diabetic rats. These results provide scientific evidence of using the parts of the said plants in the management of hyperglycemia in human beings in the traditional system of medicine and need further studies for exploring the target(s) of action of these anti-diabetic agents.
A novel footwear for type I and II diabetic patients
K. Anbarasi, J. R. JohncyLeadiah Bai 1 , T. Shantha Kumar
Departments of CSE, and 1 Bio-Medical, Alpha College of Engineering, Chennai, Tamil Nadu, India
Existing researches in early days have shown that the human activity recognition using wireless sensor have made a wide range health-related applications, in which the daily activities may provide additional information to medical doctors to accurately diagnose chronic (long-lasting) diseases like diabetes, as well as design the care plan of the patients to maintain their health status. Diabetes is also a metabolic disease affecting about 250 million of people all over the world. Patients with diabetes are at high risk for lower extremity skin breakdown and subsequent amputation. In our project, we are about to design a novel footwear with wireless sensor cater for diabetic patients. So we are using this adaline type of network that is used along wireless to sense the pressure using the sensors. Adaline is also a device consisting of a single processing element as such it is not technically a neural network. Patients develop foot deformities, secondary to muscle atrophy and imbalances, which result in high pressures under the forefoot during walking. Patients are unable to perceive that high pressure or pain on their foot due to sensory impairments.
Fisetin protects pancreatic β-cell from hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats
G. Sriram Prasath, S. Subramanian
Department of Biochemistry, University of Madras, Guindy Campus, Chennai - 600 025, India.
Persistent hyperglycemia is often associated with chronic oxidative stress which mainly contributes to the development and progression of diabetes as well as its secondary complications. The sensitivity of pancreatic β-cells to oxidative stress has been attributed to their low content of anti-oxidants compared with other tissues. Bioactive compounds with potent anti-diabetic properties have been shown to ameliorate hyperglycemia-mediated oxidative stress. Recently, we have reported that oral administration of fisetin (10 mg/kg b.w.), a bioflavonoid found to be present in strawberries, persimmon, to streptozotocin-induced experimental diabetic rats significantly improved normoglycemia. This study was aimed to evaluate the anti-oxidant potential of fisetin in both in vitro and in vivo. Fisetin treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin, with an elevation in plasma insulin. The treatment also improved the anti-oxidant status in pancreas as well as plasma of diabetic rats indicating the anti-oxidant potential of fisetin. In addition, the results of the in vitro anti-oxidant studies such as 2,2-Diphenyl-1-picrylhydrazyl and ABTS assays substantiate the free radical scavenging activity of fisetin. Histological studies on the pancreatic tissue also evidenced the tissue protective nature of fisetin. The beneficial effects of fisetin were comparable with gliclazide, a standard reference drug for diabetes. Thus, fisetin may be considered an adjunct for the treatment of diabetes.
Gossypin, a flavonolglucoside protects pancreatic beta-cells from glucotoxicity in streptozotocin-induced experimental diabetes in rats
V. Thamizhiniyan, S. Subramanian
Department of Biochemistry, University of Madras, Guindy Campus, Chennai - 600 025, India
Chronic oxidative stress caused by glucotoxicity plays a crucial role in the onset and progression of pancreatic beta-cell dysfunction in diabetes mellitus. Several studies have reported that flavonoids protect tissues from oxidative damage through its anti-oxidant potential. This study was aimed to investigate the anti-oxidant activity of gossypin by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and ABTS radical scavenging assays and its role on glucotoxicity-mediated pancreatic beta-cell dysfunction in streptozotocin-induced experimental diabetes in rats. Gossypin effectively scavenges both DPPH and ABTS radicals generated in the reaction mixtures, which implies the anti-oxidant property of gossypin. Oral administration of gossypin to diabetic rats significantly improved the anti-oxidants and reduced the levels of lipid peroxides, nitric oxide, IL-1 β, and nuclear NF-&B p65 unit in pancreatic tissues. The improved insulin content in pancreas and plasma in the experimental diabetic rats treated with gossypin as well as histological observations demonstrates the possible role of gossypin in the protection of pancreatic beta-cells. In addition, blood glucose, glycosylated hemoglobin, glutathione, lipid peroxides, IL-1 β levels in plasma, and nitric oxide level were significantly altered upon treatment with gossypin. Thus, it may be concluded that the pancreatic islet beta-cell protective role of gossypin against glucotoxicity-mediated oxidative damage might be attributed by its anti-oxidative potential.
Synthesis and evaluation of anti-diabetic properties of copper (II) hesperidin complex in streptozotocin-induced diabetic rats
V. Sendraya Perumal, S. Subramanian, V. Narayanan 1
Departments of Biochemistry, and 1 Inorganic Chemistry, University of Madras, Guindy Campus, Chennai - 600 025, India
Flavonoid-metal complexes are of great pharmacological interest as the complexes are more effective than the free flavonoids or inorganic trace metals, i.e., physiological properties of flavonoids have been used to reduce the toxicity of metals and enhance the therapeutic uses upon complexation. In this study, we have designed, synthesized, and characterized a copper (II) hesperidin complex and evaluated its anti-diabetic activity in experimental diabetic rats. Acute and chronic toxicity studies revealed the non-toxic nature of the complex. Oral administration of the copper (II) hesperidin complex at a concentration of 5 mg/kg b.w./rat/day for 30 days to diabetic rats showed significant improvement in the altered levels of biochemical parameters such as blood glucose, glycosylated hemoglobin, with concomitant improvement in plasma insulin levels. The increased levels of urea, uric acid, and creatinine were also normalized upon treatment with the complex. Further, the oral glucose tolerance test performed in experimental diabetic rats indicated the improved glucose tolerance. The results of the study indicate that copper (II) hesperidin exhibits significant anti-diabetic activity without toxicity in streptozotocin-induced diabetic rats.
Extraction, isolation, and characterization of syringin, a phenylpropanoid glucoside from Musa Paradisiaca tepal extract and evaluation of its anti-oxidant potential in streptozotocin-induced diabetic rats
C. Shanmugasundaram, S. Subramanian
Department of Biochemistry, University of Madras, Guindy Campus, Chennai - 600 025, India
Syringin, a phenylpropanoid glucoside is found to be present in the tepals of Musa Paradisiaca. Various pharmaceutical actions of syringin have been reported. In this study, an attempt has been made to extract, isolate, and characterize syringin from Musa Paradisiaca tepal extract and to evaluate its anti-oxidant nature in streptozotocin experimental diabetes in rats. Syringin scavenges both 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and ABTS radicals generated in the reaction mixtures, which indicates the free radical scavenging property of syringin. Syringin treatment showed a significant reduction in the levels of blood glucose, glycosylated hemoglobin, with an elevation in plasma insulin. The treatment also improved the anti-oxidant status in pancreas as well as plasma of diabetic rats indicating the anti-oxidant potential of syringin. Histological studies on the pancreatic tissue also evidenced the tissue protective nature of syringin. From the results obtained, it can be concluded that syringin possess potent anti-oxidant property and the presence of syringin may be responsible for the observed beneficial pharmacological properties of Musa Paradisiaca flower extract.
Ethyl acetate fractions of Xylocarpusmoluccensis and Xylocarpusgranatum display anti-diabetic and anti-dyslipidemic activities on high-fat-fed C57BL/6J db + mice
Arun K. Rawat, T. Narender 1 , Akhilesh K. Tamrkar, Arvind K. Srivastava
Divisions of Biochemistry and 1 Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Chattar Manzil Palace, M. G. Marg, Lucknow - 226 001, India
The high-fat diet-fed C57BL/6J mouse model is a robust model for impaired glucose tolerance (IGT) and early type 2 diabetes, which may be used for studies on pathophysiology and development of new therapeutic strategies. Consumption of high-fat diet rich in coconut oil to C57BL/6J db+ mice also resulted in increased body weight gain, over time a stable IGT, hyperglycemia with a progressively increased hyperinsulinemia that led to development of Insulin resistance and diabetes mellitus type 2. The objective of this study was to elucidate the anti-diabetic and anti-dyslipidemic activities of ethyl acetate fractions of Xylocarpusgranatum (CDR-134 F194) and Xylocarpusmoluccensis (CDR-267 F018), respectively, on these high-fat diet-fed C57BL/6J db+ mice. Six to eight weeks animals were kept on high-fat diet containing coconut oil (fat content 42% of energy) for 12 weeks, whereas the sham control received standard chow diet. Animals showing mild hyperglycemia and impaired oral glucose tolerance were subgrouped and treated with ethyl acetate fractions of Xylocarpusmoluccensis (CDR-267 F018) and Xylocarpusgranatum (CDR-134 F194), respectively, at a dose of 100 mg/kg body weight for 5 consecutive weeks. An average of 21 and 14% improvement on IGT was observed in CDR-134 F194- and CDR-267F018-treated groups, whereas nearly 30 and 29% lowering in serum triglyceride level, 11 and 12% lowering in total serum cholesterol level, and around 32% and 23% increase in serum HDL-C level were found in CDR-134 F194- and CDR-267 F018-treated groups, respectively. Myotubes (L6) treated in vitro with CDR-134 F194 and CDR-267 F018, respectively, showed many fold increase in PPARγ, PGC 1 α and Cox 7 and decrease in PDK 4, PDK 2, and Hmgcr. These results will be discussed in the light of anti-diabetic and anti-dyslipidemic activities of CDR-134 F194 and CDR-267 F018.
Confirmation toward establishing anti-hyperglycemic activity in some traditional Indian plants
Arvind Mishra, Rakesh Maurya 1 , Akhilesh K. Tamrkar, Arvind K. Srivastava
Divisions of Biochemistry and 1 Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow, Chattar Manzil Palace, M.G. Marg, Lucknow - 226 001, India
Diabetes mellitus is one of the most common endocrine disorders and is a major global health problem affecting more than 5% of the world's population. Herbal drugs even in the crude forms or their extracts may be more beneficial, economically viable, and socially well accepted provided their anti-hyperglycemic efficacy and safety are proven in validated animal models. Therefore, our study was focused toward the confirmation of the anti-hyperglycemic effects in crude powders, ethanolic, and aqueous extracts of different plant parts of selected traditional medicinal plants, namely Azadirachta indica, Cinnamomum tamala, Gymnema sylvestre, Emblica officinalis, Momordica charantia, Terminalia belerica, Piper nigrum, Terminalia chebula, Eugenia jambolana, Trigonella foenum graecum, and Pterocarpus marsupium. Anti-hyperglycemic effects were investigated on both normoglycemic and streptozotocin (STZ)-induced diabetic rats with or without sucrose challenge. Significant improvement in oral glucose tolerance and lowering of blood glucose were observed with one or more extracts of each plant in normal and STZ-induced diabetic rats with and without sucrose challenge. Even the crude powders of these plants turned out with similar and remarkable outcome in the above animal models. This study confirms the traditional claim of anti-hyperglycemic activity in crude powders of the parts of nearly all the above said plants and warrants for determination of their mechanism(s) of action and identification of anti-diabetic ingredients.
Influence of anti-diabetic therapy on plasma lipid profile and its relation to erythrocyte membrane lipid levels in type 2 diabetic subjects
Basavaraj S. Aski, B. B. Devarnavadagi, R. T. Kashinath, N. S. Biradar 1 , S. S. Walvekar
Department of Biochemistry, BLDE University's SRI B. M. Patil Medical College, 1 Department of Medicine, Alameen Medical College, Bijapur, India
The diabetes-induced plasma dyslipidemia possibly may lead to an alteration in red blood cells (RBC) membrane cholesterol/phospholipids ratio in diabetic subjects resulting in a possible alteration in RBC membrane properties. It has been observed in our laboratory, such a change occurs in type 2 diabetic subjects. The effect of various oral anti-diabetic drugs and or insulin on diabetes-induced RBC membrane alteration is not known. Hence, this work was undertaken to establish the influence of anti-diabetic drugs and or insulin on RBC membrane lipid levels in type 2 diabetic subjects. Blood samples from randomly selected type 2 diabetic subjects attending medical OPD of Sri B. M. Patil Medical College and Hospital, Bijapur and Alameen Medical College and Hospital Bijapur, were collected after obtaining written consent. The plasma lipids as well as RBC membrane lipids were estimated. The study group includes normal subjects (group-1), diabetics (group-2), diabetics receiving oral drugs (group-3), diabetics receiving insulin (group-4), and diabetics receiving both oral drugs and insulin (group-5). The study suggests an increase in plasma lipid levels with a parallel raise in RBC membrane lipid composition in diabetic subjects and hypoglycemic drugs, insulin combined therapy regime may help to control the diabetic dyslipidemia-induced erythrocyte membrane lipid alterations.
Ethnobotanical survey on medicinal plants used to treat diabetes mellitus in Chidambaram
B. Vinoth, R. Manivasagaperumal
Department of Botany, Annamalai University, Annamalai Nagar - 608 002, Tamilnadu, India
Diabetes mellitus is a chronic disorder of carbohydrate metabolism characterized by increased fasting and post-prandial blood sugar levels. Traditional medicines derived from medicinal plants are used by 60% of the World's population. Herbal medicine is gaining popularity both in developing and developed countries because of their natural origin and less side effects. The herbal drugs with anti-diabetic activity are yet to be commercially formulated as modern medicines, even though they have been acclaimed for their therapeutic properties in the traditional systems of medicine. Medicinal plant treatments have been used throughout the World for the therapy of diabetes mellitus. Among many medications and other alternative medicines, several herbs have been known to control diabetes; additionally, they have no side effects. This paper is an attempt to list the plants which have been used to treat diabetes by the traditional healers in Chidambaram. List of those medicinal plants and their common name, botanical name, family, and various uses will be discussed and could help the forth coming researchers to work on diabetes mellitus.
Hypoglycemic properties of Tinospora cardifolia in allaxon induce diabetic rats
G. Chandran, M. Chandran
Department of Zoology, Thiagarajar College, Madurai - 9, India
Diabetes mellitus, currently, is a major health problem for the people of the world and is a chronic metabolic disorder resulting from a variable interaction of hereditary and environmental factors. The number of people suffering from the disease worldwide is increasing at an alarming rate with a projected 366 million peoples likely to be diabetic by the year 2030 as against 191 million estimated in 2000. Though we cannot cure diabetes, but we can control the diabetes with the help of allopathic treatment in the term of tablets or insulin injection. The side effect due to allopathic treatment is one of the unavoidable problems. Actually, the phytocompounds present in the Tinospora cardifolia has ability to rejuvanate and induce the multiplication of beta-cells present in the islets of Langerhans. Hence, in this investigation, the plant T. cardifolia extract was chosen to evaluate its anti-diabetic potential.
Evaluation of anti-diabetic properties of Mimosa Pudica in streptozotocin-induced diabetes in rats
R. Deepa, S. Subramanian 1
Departments of Biochemistry, Madha Dental College and Hospital, 1 University of Madras, Guindy Campus, Chennai, India
Diabetes mellitus is a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances of carbohydrate, fat, and protein metabolism, resulting from defects in insulin secretion, insulin action, or both. Nowadays, it is one of the leading causes of morbidity and mortality. The treatment of diabetes mellitus by pharmaceutical drugs leads to undesirable side effects and moreover too expensive. Recently, the medicinal plants play an important role in the management of diabetes mellitus. The aim of this study is to evaluate the anti-diabetic properties of Mimosa pudica in streptozotocin (STZ)-induced diabetes in rats. Male Wistar albino rats were randomly assigned into five groups of six animals each: Control, diabetic control (STZ induced), diabetic and drug, diabetic and standard drug (Glibenclamide), and drug alone. After 30 days of treatment, rats were sacrificed and the biochemical parameters such as blood glucose, total hemoglobin and glycosylated hemoglobin, urea, creatinine, and serum enzymes were determined. Mimosa pudica leaves extract administered to diabetic rats for 30 days significantly reduced the levels of blood glucose, glycosylated hemoglobin, urea, and creatinine, and significantly increased total hemoglobin. These data indicate that Mimosa pudica can act as an effective anti-diabetic and thereby promoting healthy longevity to live a healthy life.
Anti-diabetic activity of Cardiospermum halicacabum L. leaf extract on streptozotocin-induced diabetic rats
Krishnan Baskaran, Ramalingam Saravanan, Kodukkur Viswanathan Pugalendi
Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, India
Cardiospermum halicacabum L. (CH) is widely used in Indian medicine to treat various diseases. This study was undertaken to investigate the anti-diabetic activity of leaf extract of CH on streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in adult male albino Wistar rats (weighing 180-200 g) by administration of STZ (40 mg/kg b.w) intra-peritoneally. The diabetic rats showed an increase in blood glucose, glycated hemoglobin (HbA1c) and decrease in body weight, plasma insulin, and blood hemoglobin (Hb). The three different CH leaf extracts (chloroform, ethanol, and ethyl acetate) were administered orally to the diabetic rats at 100 mg/kg b.w dose for 45 days. The diabetic rats restored the blood glucose, HbA1c levels, and improved the body weight, plasma insulin, blood Hb to near normal. Among the three different leaf extracts, ethyl acetate extract of CH showed maximum activity. This investigation concludes that the leaf extract of CH possesses anti-diabetic activity.
Impact of probiotics on glycemic and anti-oxidative status with implications on neurotransmitters in diabetic animal models
Sandhya Gaekwad, Pelekhrienuo Kire, S. Sasikala, Dharshit Shah 1 , Kannan Eagappan, K. Kanjana
Department of Clinical Nutrition and Dietetics, PSG College of Arts and Science, 1 Department of Pharmacology, PSG College of Pharmacy, Coimbatore, India
To explore the beneficial use of probiotics in diabetic albino rats, changes in body and brain weight and to check its impact on neurotransmitters. The study was carried out for 30 days. Streptozotocin (30 mg) was used to induce diabetes in two groups: Treated and untreated groups. A third group served as a healthy control. Lbcasei and rhamnosus (75 mg/kg body wt) were administered daily to the treated group intra-peritoneally, whereas insulin (1 unit) was administered daily to the untreated group intra-muscularly. On every 3 rd consecutive day, blood glucose was measured and body weight of the animals was recorded once a week. On the 31 st day, all animals were sacrificed, and the brain was weighed and the levels of neurotransmitters, glutamate, aspartate, and GABA, were estimated. Anti-oxidant status was assessed by measuring levels of superoxide dismutase (SOD), reduced glutathione (GSH), and thiobarbituric acid (TBARs) in the blood. Glycemic control was better in the insulin (untreated) group when compared to the probiotic (treated) group. Weight loss was more in the treated group, which could be attributed to the poorer glycemic control seen in that group. Though the glycemic control in the probiotic group was not equivalent to that of the insulin group, the absence of morbidity itself is a significant finding. No changes were seen in brain weight in both groups. With reference to anti-oxidative status, there was no significant difference in the SOD and TBARS between treated, untreated, and control groups. GSH levels were higher in the probiotic (treated) group. Also the mean concentrations of neurotransmitters were found to be on higher side in the treated and untreated groups when compared with the control group, which may be attributed to diabetes per se as such. There was also a pronounced deviation in GABA concentration in the treated group compared to control and untreated groups, in an exponential manner. GABA is a counter-regulatory neurotransmitter to the excitatory neurotransmitters, aspartate and glutamate. The exponential increase in GABA could be due to its increasing to neutralize the consequences of the excitatory neurotransmitter. The absence of any morbidity in diabetic rats treated only with probiotics and no other hypoglycemic agents is suggestive of a future possible role as an adjunctive therapeutic agent in diabetes mellitus.
Evaluation of magnesium and blood lipid levels in type II diabetes mellitus
B. B. Devaranavadgi, S. S. Devaramani, B. S. Aski, Indira Hundekari, Surendra Naik, R. T. Kashinath 1
Department of Biochemistry, BLDEU's Shri B. M. Patil Medical College, Bijapur - 586 103, 1 Department of Biochemistry, Subbaiah Institute of Medical Sciences, Shimoga, Karnataka, India
Diabetes mellitus is one of the most common metabolic disorders. The incidence of diabetes is increasing globally and in India. Magnesium depletion has a negative impact on glucose homeostasis and insulin sensitivity in patients with type II diabetes mellitus. Magnesium deficiency can lead to development of complications such as retinopathy, thrombosis, and hypertension. Hence, the study was planned to assess FBS and PPBS, serum Mg, urea, creatinine, and blood lipid levels in type II diabetes mellitus. One hundred type II diabetic patients attending diabetic clinic at BLDEU's Shri. B. M. Patil Medical College Hospital and Research Centre, Bijapur were compared with 100 non-diabetic age- and sex-matched controls. In our study, we observed 37% of diabetic patients had low serum Mg levels and 9% of non-diabetic controls had low serum Mg levels. Thus, type II diabetic patients had higher incidence of lower serum Mg levels as compared with the age-and sex-matched non-diabetic controls. Hence, we support the need of supplementation with Mg in diabetic patients who have proven hypomagnesaemia and the presence of its complications.
Effect of Padina tetrastromatica on carbohydrate metabolism of high-calorie-fed/streptozotocin-treated diabetic rats
D. S. Mohan, S. Mini, G. Muraleedhara Kurup
Department of Biochemistry, University of Kerala, Kariavattom Campus, Thiruvananthapuram - 695 581, Kerala, India
Diabetes mellitus, the fastest growing health challenge facing humanity is a manifestation of metabolic disturbances due to the dietary intake of excess carbohydrates and lipids. It is characterized by insulin insufficiency and/or insulin dysfunction. This study was designed to simulate the natural history and metabolic characteristics of human type II diabetes in rats and its treatment with Padina tetrastromatica, edible marine brown algae. The rats, except the controls were fed with high-calorie diet for 2 months and then were intra-peritoneally injected with streptozotocin (15 mg/kg bwt). Effect of oral administration of 80% aqueous methanolic extract (150, 300, 450, and 600 mg/kg bwt) for 30 days on the levels of serum glucose, glycated hemoglobin, liver, and muscle glycogen and the activities of hepatic hexokinase and gluconeogenic enzymes were evaluated. Administration of the extract significantly decreased serum glucose and glycated hemoglobin in a dose-dependent manner. The hepatic and muscle glycogen which was decreased in the diabetic control group retained to normal upon treatment. The activity of hexokinase was decreased and those of the gluconeogenic enzymes get increased in the liver of diabetic control group, whereas the treatment tends to restore the normal levels. Hence, it can be concluded that, the extract at a dose of 450 mg/kg bwt should be considered an excellent candidate for future studies of obesity-associated experimental diabetes mellitus.
Estimation of thyroid hormones in patients with type II diabetes mellitus
Department of Biochemistry, Shri B. M. Patil Medical College, Bijapur - 586 103, Karnataka, India
Diabetic patients have a higher prevalence of thyroid disorders compared to normal population because patients with one organ-specific autoimmune disease are at risk of developing other autoimmune disorders. In the general population, approximately 6% of people have some form of thyroid disorder. However, the prevalence of thyroid disorder increases to over 10% in people with diabetes. There is a higher occurrence of thyroid diseases, particularly hypothyroidism, among people with type 2 diabetes. Sixty subjects comprising of 30 healthy controls and 30 type 2 diabetes mellitus cases were studied. In all the subjects, fasting blood glucose, serum thyroid stimulating hormone (TSH), serum tetraiodothyronine (T4), and serum triiodothyronine (T3) were estimated. TSH levels were increased in diabetic patients (7.56 ± 8.4, P < 0.05) when compared to controls (2.75 ± 2.00) which was statistically significant. However, serum T3 (cases: 0.93 ± 0.44, controls: 1.00 ± 0.35, P < 0.488) and T4 (cases: 6.87 ± 2.41, controls: 7.40 ± 2.05, P0 < 0.799) levels were within the normal range. Since thyroid disorders and diabetes mellitus have a common autoimmune etiology, diabetic patients having increased TSH could be due to immunological disturbances and is suggestive of diabetic patients probably suffering from subclinical hypothyroidism.
Diabetes and its treatment in Ayurvedha
B. Jayaprasad, B. Jayagowri, P. S. Sharavanan
Department of Botany, Annamalai University, Annamalainagar, Tamil Nadu, India
Diabetes mellitus is termed as silent killer and recently evidence of cases of "Insulin resistance" and the occurrence of side effects from prolonged administration of conventional drugs has triggered the search for safe and effective alternatives. In Ayurvedha, all the diseases are diagnosed on the basis of Vatha, Pitha, and Kapha by means of naadi. Ancient science of Ayurveda has discussed diabetes at length thousands of years ago. The knowledge and effectiveness of diagnosis can be understood with the fact that Ayurveda has classified diabetes (Prameha) into 20 types, Kaphajaprameha (subdivided into 10 types), Pittajaprameha (subdivided into 6 types), and Vatajaprameha (again subdivided into 4 types). In these three types of prameha, Kaphajaprameha and Pittajaprameha are curable and vatajaprameha cannot be cured. Ayurvedic practitioners use diet modification, Panchakarma, several herbal preparations for the treatment of diabetes. Exercise is another cornerstone of ayurvedic treatment toward diabetes. Yoga and breathing exercises are traditionally used. This paper discusses the above information in detail.
Nitric oxide mediates the insulin sensitivity effects of β-sitosterol in high-fat diet-fed rats
M. K. Radika, C. V. Anuradha
Department of Biochemistry and Biotechnology, Annamalai University, Annamalai Nagar - 608 002, India
The objective of the study is to investigate the protective effect of β-sitosterol on high-fat-fed rat model of insulin resistance (IR) and to assess whether nitric oxide (NO) is involved in its action. Adult male albino Wistar rats of body weight 150-180 g were fed either control diet (CON) or high-fat diet (HFD). Each dietary group was divided into two: Treated or untreated with β-sitosterol (10 mg/kg b.w.-1 day-1) for 4 weeks. Inhibition of total nitric oxide synthase (NOS) by administration of nitro-L-arginine methyl ester (L-NAME) and inducible NOS (iNOS) by aminoguanidine (AG) in HFD and HFD+ β-sitosterol groups were accomplished to identify the role of NO. HFD-fed rats showed hyperglycemia, hyperinsulinemia, IR, oxidative damage, nitrosative stress, lipid accumulation, and elevated serum aminotransferases. Increased expression of iNOS and decreased expression of endothelial NOS (eNOS) were observed in them. Hepatic fat accumulation was further confirmed by histology. The abnormalities associated with HFD feeding were significantly reduced by β-sitosterol. L-NAME administration for the last 7 days to β-sitosterol-treated HFD rats abolished the glucose lowering effect of β-sitosterol, but the ability to decrease oxidative stress remained unaltered. Administration of AG resulted in improved glucose homeostasis and anti-oxidant levels but decreased oxidative stress and enhanced anti-oxidant potential in both HFD and HFD + β-sitosterol-treated groups. Thus, β-sitosterol promotes insulin sensitivity in rats fed HFD possibly by improving NO levels.
QSAR-based designing of specific inhibitors to aldose reductase 2 playing crucial roles in chronic diabetic complications
Gudimalla Shashikanth, Thirunavukkarasu Sivaraman
Department of Bioinformatics, Structural Biology Lab, School of Chemical and Biotechnology, SASTRA University, Thanjavur - 613 401, India
In diabetics, elevated glucose concentrations are often being converted into sorbital by aldose reductase (ALR2) in polyol pathway. It has been documented that ALR2 is the culprit for diabetic complications involving a number of organs as the enzyme present in many parts of humans such as retina, cornea, myelin sheath, placenta, and red blood cells. In the present studies, we have developed a 3D-QSAR model inhibitor to the enzyme, based on 118 flavonoids derivatives for which IC 50 values have been reported in the literature. Of the 251 models generated, a model consisting of six pharmacophore features (AADHRR) was selected for similarity searches as the model yielded better regression value of 0.775 vis-ΰ-vis other models, upon fitting the data representing 3D structural alignments of the reported ligands with the model pharmacophore structure, to the standard least-square equations. Using a best-fitted analogue of flavonoids derivatives obtained from the 3D-QSAR model, as a seed, a small focused-combinatorial library containing 200 de novo inhibitors to the enzyme was generated and the compounds were subjected to affinity filter, bioavailability filter, and toxicity filter using an array of computational tools. Combined comprehensive analysis on the data obtained from the various filters resulted in a few numbers of efficient de novo inhibitors against the enzyme. The structural features of the lead compounds have been brought into fore in detail.
Telemedicine in the treatment of diabetes mellitus
Sri Nandhanam Group of Instituitions, Tirupattur - 635 601, Tamil Nadu, India
Diabetes is a metabolic disorder characterized by insulin deficiency. The diabetic patients require continuous monitoring under the care of a diabetic expert. In some remote places or patient under critical condition, it is impossible to take such a continuous care. To overcome these problems and conditions, the modern technology talks a lot about tele-medicine or tele-treatment. Therefore, this paper talks about some important aspects of tele-medicine and treatment available for treating diabetes through modern technologies like wireless communication which includes mobile communication, internet connection, etc.
Studies on the hypoglycemic properties- Tephrosia purpurea
K. Umamaheswari, M. Chandran
Department of Zoology, Thiagarajar College, Madurai - 9, India
Diabetes mellitus is a group of disorders with different etiologies and it is characterized by derangements in carbohydrate, protein, and fat metabolism caused by the complete or relative insufficiency of insulin secretion or insulin action. It is associated with several long-term complications, including retinopathy, nephropathy, neuropathy, and angiopathy. The diabetes mellitus increases with increasing proportion of the aging population, consumption of calorie-rich diet, obesity, and sedentary lifestyle which have led to a tremendous increase in the number of diabetics worldwide. The allopathic treatment for diabetes mellitus quickly regulates the hyperglycemic condition; at the same time, it creates various side effects in long-term treatment. To avoid the side effects due to allopathic treatment, both the patient and researcher more eager to investigate the new alternate methods to cure the diabetes mellitus. In India, 30-40 years before, all the people used the herbal medicine to cure all types of diseases. Hence, this study has been programmed to screen the plant Tephrosia purporea for hypoglycemic activities.
Evaluation of anti-oxidant and anti-carcinogenic activities of wheatgrass and analysis of bioactive constituents
Garima Shakya, Kumaravel Mohankumar, Sankar Pajaniradje, Muddasarul Hoda, Rukkumani Rajagopalan
Department of Biochemistry and Molecular Biology, School of Life Sciences, Pondicherry University, Puducherry, India
Cancer is the second leading cause of death worldwide and oxidative stress is responsible for causing cancer. Toxic effects of chemotherapeutic drugs cause severe reduction in quality of life. Anti-oxidants play a very important role in the prevention of cancer. Therefore, efforts have been made to identify natural anti-oxidants having anti-cancer potential. Various herbs, fruits, and vegetables have diverse phytochemicals that display anti-oxidant properties and help in reducing the risk of cancer. Wheatgrass has a potent anti-oxidant efficacy and has been used as a health drink and is used to cure many diseases in folk medicine. Hence, in this study, we tested the anti-oxidant and anti-cancer effects of wheatgrass. Different extracts of wheatgrass were tested for anti-oxidant abilities such as ferric reducing power, total anti-oxidant assay, and nitric oxide radical scavenging activity. The best solvent extract was further evaluated for anti-proliferative activity in Hep2 cells. The bioactive constituents were analyzed by gas chromatography-mass spectroscopy (GC-MS). Methanol extract showed high quantity of phenols and flavonoids and GC-MS analysis showed the presence of nine bioactive phytoconstituents. It had good anti-oxidant and anti-proliferative activity. From our study, we conclude that wheatgrass has good anti-oxidant property and being a natural product it could be safe for cancer treatment.
Screening of common variants in abra1 of breast cancer patients in South India
Dakshina Moorthy Janani, R. K. Shalini, Rekha Namachivayam, M. Parani
Department of Genetic Engineering, SRM University, Chennai, India
Breast cancer is the most common type of cancer affecting women worldwide. According to AIIMS, New Delhi, the rate of breast cancer in Indian metro cities is likely to increase from 21.7 to 28.7% by 2015. Several genes have been reported to associate with the breast cancer, viz., BRCA1, BRCA2, p53, etc. A recent study on Finland breast cancer patients, a novel gene Abraxas, is found to be associated with breast cancer. Abraxas is a protein in BRCA-associated complex. Abraxas is required for the localization of BRCA1 complex to DNA damage foci and takes part in DNA damage repair pathway. We are screening for mutations in Abraxas gene (ABRA1) in clinically proven breast cancer patients among south Indian population. In our study, 300 samples including both sporadic and familial cases will be analyzed for nine coding exons of ABRA1. We emphasize on future studies of mutations in Abraxas gene and its prevalence in Indian scenario to use it as a marker for early diagnosis and targeted therapies.
Protective effects of naringin on modulating anti-oxidant and lipid peroxidation in DEN-induced hepatocellular carcinoma rats
T. Prabu, V. Manju
Department of Biochemistry, Periyar University, Salem - 11, India
The study aims at elucidating the anti-oxidant efficacy of naringin in N-Nitrosodiethylamine (DEN)-induced rat liver carcinogenesis. Administration of naringin (40 mg/kg BW orally) for 16 weeks to DEN-induced (200 mg/kg BW in drinking water) rats offered protection against the oxidative stress and thereby prevented liver carcinogenesis. DEN induction in experimental animals resulted in increased activities of liver marker enzymes (AST, ALT, ALP, and LDH), albumin, bilirubin, total protein, and lipid peroxide levels and decreased levels of anti-oxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase). Naringin treatment restored the elevated activities of liver marker enzymes and anti-oxidant status to near normal with decreased lipid peroxide. Histological observations of liver tissue too correlated the above biochemical findings. Hence, these results clearly suggest that naringin treatment prevents liver damage, lipid peroxidation, and protects the anti-oxidant defense system in DEN-induced liver carcinogenesis in rats.
Effect of D-Pinitol on the apoptosis of human breast cancer cell line MCF-7
T. Rengarajan, N. Nandakumar, M. P. Balasubramanian
Department of Pharmacology and Environmental Toxicology, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai - 600 113, India
The aim of this study was to investigate the impact of a dietary D-Pinitol on the human breast cancer cell line (MCF-7) and its possible role in the induction of apoptosis. Human breast cancer cells were treated with different concentrations of D-Pinitol and its cytotoxicity effect was measured by MTT method and lactate dehydrogenase leakage assays. Apoptosis was analyzed by light microscopic studies and DNA fragmentation. The mechanism of apoptosis was studied with the expression of p53, Bcl-2, and caspase-3 proteins. Glutathione content, reactive oxygen species, and mitochondrial membrane potential were also measured in MCF-7 cells after D-Pinitol treatment. The results revealed that D-Pinitol significantly inhibited the proliferation of MCF-7 cells in a concentration-dependent manner. Apoptotic morphology was observed in MCF-7 cells treated with D-Pinitol at the concentration of 60 and 80 μM. DNA fragmentation, accumulation of p53, Bcl-2, and expression of caspase-3 proteins were observed in MCF-7 cells after the treatment with D-Pinitol. The depletion of GSH and an elevation of LDH were observed in MCF-7 cells treated with D-Pinitol. Therefore, in conclusion, D-Pinitol induced cytotoxicity in MCF-7 cells in vitro. Apoptosis of MCF-7 cells may be due to the DNA damage and expression of apoptotic proteins. Depletion of GSH may be involved in the induction of apoptosis of Michigan cancer foundation-7 cells.
In vitro anti-cancer activity of marine clam Anadara granosa (linn.) against HeLa cell model using comet assay
J. Anusuya, S. Hemalatha
Department of Zoology, Annamalai University, Annamalainagar - 608 002, Tamil Nadu, India
Marine organisms have to withstand extreme variation in pressure, salinity, temperature, etc., and these environmental valuables have facilitated the organism to produce varied chemicals of unique features. Many of these secondary metabolites possess biological activities with implications for application as antibiotic, anti-parasitic, anti-viral, and anti-cancer agents. In this study, screening of different extracts of whole body (methanol, chloroform, and acetone extracts) from Anadara granosa has been conducted using the in vitro comet assay for anti-cancer using HeLa cell lines. Among the three extracts, methanol extract showed significant (P ≤ 0.005) anti-cancer activity. These results indicate that methanol extract of A. granosa effectively inhibits in vitro HeLa cell multiplication by inducing DNA damage to these cancer cells.
Anti-cancer, DNA cleavage, and anti-microbial activity of some homodinuclear lanthanide complexes of phenylthiopropionic acid
C. Shiju, D. Arish S. Kumaresan
Department of Chemistry, Manonmaniam Sundaranar University, Tirunelveli - 627 012, 1 Center for Scientific and Applied Research, P. S. N. College of Engineering and Technology, Tirunelveli - 627 152, Tamilnadu, India
Corresponding Author: Dr. Shanmugam manoharan Reader, Dept of Biochemistry and Biotechnology, Annamalai University, Annmalai Nagar, 608 002, India. Ph: +91 4144 238343/Fax: +91 4144 238141
Email: [email protected], [email protected]
Lanthanide complexes of La(III), Pr(III), Nd(III), Sm(III), and Ho(III) with phenylthiopropionic acid were synthesized and characterized by elemental analysis, mass, IR, electronic spectra, molar conductance, TGA, and powder XRD. The results show that the lanthanide complexes are homodinuclear in nature. The two lanthanide ions are bridged by eight oxygen atoms from four carboxylate groups. Thermal decomposition profiles are consistent with the proposed formulations. Powder XRD studies show that all the complexes are amorphous in nature. Anti-microbial studies indicate that these complexes exhibit more activity than the ligand itself. The DNA cleavage activity of the ligand and its complexes were assayed on E. coli DNA using gel electrophoresis in the presence of H 2 O 2 . The result shows that the Pr(III) and Nd(III) complexes have completely cleaved the DNA. The anti-cancer activities of the complexes have also been studied toward human cervical cancer cell line (HeLa) and colon cancer cells (HCT116) and it was found that the La(III) and Nd(III) complexes are more active than the corresponding Pr(III), Sm(III), and Ho(III) complexes, and the free ligand on both the cancer cells.
Ameliorating effect of Curcuma amada against cancer and oxidative stress
K. Gowri, C. Elanchezhiyan, S. Suhasini, Bilal Ahmad Bhat
Department of Zoology, Annamalai University, Annamalai Nagar - 608 002, India
This study was aimed to investigate the anti-cancer and anti-oxidant activity of a storage form of Curcuma sp. namely Curcuma amada mango ginger rhizome. No significant changes were observed in pH, titrable acidity, and total soluble solids of the rhizomes stored at different temperatures, viz., room temperature (25C), low temperature (14C), and chilling temperature (4C). The total phenol contents of the aqueous rhizome extracts of C. amada were 41.25 mg gallic acid equivalents/g dry material. The reducing power and superoxide, ABTS and DPPH radical scavenging activities of C. amada were very significant. These results supported that C. amada could be an economically important plant species due to its high anti-oxidant and anti-cancer potential.
Cancer and diabetes treatment with herbal plants
S. Kaveriammal, A. Subramani 1
Department of Plant Biology and Plan Biotechnology, Government Thirumagal Mills College, Gudiyattam, Vellore, 1Department of Botany, Arignar Anna Govt. Arts College, Villupuram - 605 602, India
Ayurveda is one of the most widely practiced systems of the Indian traditional medicine, but there are others such as siddha and unani, used in the Indian subcontinent. According to World Health Organization, 76 million people died of cancer and diabetes treatment. For cancer and diabetes, Azadirachta Indica, Arabic Acacia, curcuma longa Rhizome, Vaccinium stamineum, and Terminalai arjuna are used for the present paper discussion about the importance of above-mentioned medicinal plants.
Modulating effect of Apigenin on the expression pattern of cell-proliferative, apoptotic, inflammatory, and angiogenic markers during 7,12-dimethylbenz[A] anthracene-induced hamster buccal pouch carcinogenesis
Simon Silvan, Shanmugam Manoharan 1
Acharya Arts and Science College, Acharyapuram, Villianur - 605 110, 1 Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar - 608 002, Tamil Nadu, India
Aim was to investigate the modulating effect of apigenin on expression pattern of apoptotic (p53, Bcl-2, Bax, and Caspase-3 and 9) cell proliferative (PCNA, Cyclin D1, c-fos), angiogenic (VEGF), and inflammatory (NF͖B, COX-2) markers during 7,12-dimethylbenz[a] anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral squamous cell carcinoma was developed in the buccal pouches of golden Syrian hamsters by painting with 0.5% DMBA three times a week for 14 weeks. Abnormal expression pattern of cell proliferative, apoptotic, inflammatory, and angiogenic markers was noticed in hamsters treated with DMBA alone. Oral administration of apigenin at a dose of 2.5 mg/kg b.w modulated the above-mentioned molecular markers toward suppression of cell proliferation in hamsters treated with DMBA. The anti-cell proliferative, anti-inflammatory, anti-angiogenic, and apoptotic potential could be responsible for the inhibition of tumor formation during DMBA-induced hamster buccal pouch carcinogenesis.
Influence of melatonin on the status of lipid peroxidation and anti-oxidants during N-nitrosodiethylamine-induced liver carcinogenesis in mice
V. Devi, P. Subramanian
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar - 608 002, Tamil Nadu, India
Hepatocellular carcinoma is a major public health burden in all countries. Lipid peroxidation has been implicated as a major cause in cancer development. In this study, we investigated the effect of melatonin on N-nitrosodiethylamine-induced liver cancer in mice (Mus booduga). N-nitroso compounds are known hepato-carcinogens and cause liver necrosis. N-nitrosodiethylamine increases the lipid peroxidation products (thiobarbituric acid reactive substances and lipid hydroperoxides) and significantly decreased the anti-oxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase levels. Administration of melatonin significantly reduced the liver marker levels and simultaneous elevation in anti-oxidant levels. On the basis of these findings, we concluded that melatonin as a potent endogenous anti-oxidant and free radical scavenger, melatonin could possess anti-carcinogenic effects.
Evaluation of chemopreventive response of silibinin and its nanoparticles in experimental oral carcinogenesis using light-induced autofluorescence spectroscopy
M. Gohulkumar, S. Shaiju Nazeer 1 , R. S. Jayasree, N. Krishnakumar
Department of Physics, Annamalai University, Annamalainagar - 608 002, Tamilnadu, 1 Biophotonics and Molecular Imaging Lab, Biomedical Technology Wing, Poojappura, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram - 695 011, Kerala, India
Autofluorescence spectroscopy is an emerging optical technique used for real-time cancer diagnosis. The aim of this study is to investigate the chemopreventive effects of prepared silibinin-loaded nanoparticles relative to efficacy of free silibinin (SIL) in modifying the carcinogenic process and to study the changes in the endogenous fluorophores during DMBA-induced oral carcinogenesis by light-induced autofluorescence (LIAF) spectroscopy. LIAF emission spectra from the hamster buccal mucosa of the control and the experimental groups of animals were recorded in the 400-700 nm spectral range on a miniature fiber optic spectrometer from different anatomical sites of each group, with excitation at 405 nm. Oral squamous cell carcinoma was developed in the buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. DMBA-painted animals revealed the morphological changes, hyperplasia, dysplasia, and well-differentiated squamous cell carcinoma. LIAF emission spectra showed significant difference between the control and tumor tissues. The tumor tissues are characterized by an increase in the emission of porphyrins and a decrease in the emission of nicotinamide adenine dinucleotide hydrogenase and flavin adenine nucleotide when compared to the control tissues. Furthermore, oral administration of SIL and its nanoparticulates restored the status of endogenous fluorophores in the buccal mucosa of DMBA-painted animals. On a comparative basis, the treatment of nanoparticulate silibinin was found to be more effective than free silibinin in improving the status of endogenous porphyrins to a normal range in DMBA-induced hamster buccal pouch carcinogenesis. The result of this study further suggests that LIAF spectroscopy may be a very valuable tool for rapid and sensitive detection of endogenous fluorophores changes in response to chemopreventive agents.
Heroic roles of biological micro electro mechanical system/nano electro mechanical system in cancer therapy
S. H. Fathima Naseem
Sri Nandhanam Polytechnic College, Tirupattur - 635 601, Tamil Nadu, India
Treating the diseases without side effects is a challenge in medical field. Diabetes mellitus, cardiovascular diseases, and cancer are the outstanding diseases of human beings that require efficient treatment in controlling the diseases. Biological micro electro mechanical system/nano electro mechanical system (Bio-MEMS/NEMS) is one of the new emerging biotechnologies which are used in treatment of various diseases. Targeting, small and more controlled drug dosing, reduced toxicity, and less invasive are the advantages of bio-MEMS/NEMS in cancer therapy. Because these techniques include direct delivery of drugs into the targets like tumor cells with the least side effects when compared to the other existing cancer therapies like chemotherapy, radiation, hormone therapy, and surgery. This paper illustrates bio-MEMS/NEMS in cancer therapy in vivo level and could inspire the young budding scientists to come out with successful solutions in treating tumors in near future.
In vitro anti-cancer and anti-bacterial activity of selected sea weeds collected from Gulf of Mannar
A. Shibu, S. Dhanam 1
Departments of Botany, Government Thirumagal Mills College, Gudiyattam, 1Government Arts and Science College, Vilupuram, India
Anti-cancer activities of some selected seaweed extracts are obtained from the marine algae. Enteromorpha intestinilas, Ulva lactuca, Dictyota dichotorna, and Padina boergesinii were investigated. The extracts have been taken from acetone, benzene, and chloroform and were assessed against the human breast adenocarcinoma cell lines DU145, LNCaP, and PC3 using the cytotoxic assay, in vitro. The crude extract of E. intestinilas showed strong cytotoxic activity against the DU-145 cell line and it showed less than 10% viability after treatment. It is found that the algal extracts have also anti-bacterial activity against the following bacteria: Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Escherichia coli. The maximum inhibitory activity was seen against S. pneumoniae and E. coli.
Herbal treatment to cure breast cancer
B. Kalapana, S. Lakshmi 1
1 Department of Botany, Government Thirumagal Mills College, Gudiyattam - 632 602, 1 Department of Botany, A.A. Government Arts College, Villupuram - 605 602, India
A wide variety of alternative breast cancer treatments such as acupuncture, massage, megavitamins, herbal supplements, nutrition, and magnetic therapy are available in India. Herbal supplements are plant extracts and have long been used for a variety of health purposes. The fact is that herbal supplements can act like a drug and may be harmful when taken in large amount. Prevention and treatments to breast cancer through tumor lifting, chemotherapy, or radiotherapy are restrained not long, cancer will grow up again. It is not surprise if patients then trying to alternative treatment using herbal therapy. Garlic in raw or in powder form, broccoli in raw and powder forms, grapes, wheat-grass in a raw form or juice, green tea, and soyabean are used as efficient anti-breast cancer agents and beneficial diets such as cucumber, carrot, banana, spinach, and peas are also used to get rid of pain from cancer.
Anti-cancer properties of Piper nigrum (L.)
P. S. Sharavanan, B. Jayaprasad
Department of Botany, Annamalai University, Annamalai nagar - 608 002, Tamil Nadu, India
Plants are one of the most widely used medicines in the world today due to its less side effects over synthetic drugs. Today, herbal products as remedy or medicine have experienced an explosive growth and profitable popularity. The vast majority of primary lung cancers are carcinomas of the lung, derived from epithelial cells. Lung cancer is responsible for the most cancer deaths in both men and women throughout the world. Epidermal growth factor receptor (EGFR) signaling is a main pathway driving lung cancer. The EGFR is a transmembrane glycoprotein with an extracellular ligand-binding domain and an intra-cellular domain possessing intrinsic tyrosine kinase activity. The silencing of the EGF may reduce the risk of cancer cell growth. In this work, an attempt was made to find a novel inhibitor for lung cancer using in silico approach. The lung cancer target EGFR was identified and the structure was modeled. The modeled structure was validated to ensure the stereochemical quality of the 3D structure. Medicinal plants have been used for centuries as remedies for human diseases because they contain components of the therapeutic value. Piper nigrum has been used as a spice in India since pre-historic times and has medicinal properties as well. The medicinal and pharmacological activities are mainly due to the presence of phytochemicals. The active compounds of Piper nigrum were screened and Molecular Docking analysis was carried out between the receptor and the active compounds of Piper nigrum, which provide a theoretical support for the interaction studies between the compounds and receptor from the binding affinity and dock score of the docked complex. The best active compounds were screened based on the dock score and binding energy of the docked complex. The docking studies showed that piperine and caffeic acid have the highest score. The above study demonstrates that the compound piperine and caffeic acid show more activity against lung cancer. The studies reveal that piperine and caffeic acid have potent anti-tumor inhibiting potential against lung cancer.
Cancer risk among cadmium elevated women in Madurai District
N. Sasirekha, M. Chandran
Department of Zoology, Thiagarajar College, Madurai - 9, India
Breast cancer is the second leading cause of cancer mortality in women aged 55-74 years. It has a lifetime incidence rate of one-in-eight, or 12.6%. It is of great importance to understand which environmental factors might lead to increased risk for breast cancer. In particular, trace metals are known to have a variety of adverse health effects. To find this, many studies have been conducted on their possible carcinogenic properties in humans. Among these, few studies suggested that the cadmium might also cause early puberty and possibly breast cancer. It has shown that even low doses and short-term exposure to cadmium can cause specific DNA damage in breast tissue and may be a possible mechanism of action of cadmium on the cell cycle of human mammary cell lines. Cadmium exposure was found to be associated with a 2-fold increase in risk for breast cancer. Cadmium is a naturally occurring metal found in soil, rocks, and water. Human exposure to cadmium is frequent through food and industrial exposure because they are frequently dumped together with household waste, thereby contaminating the environment. Hence, this study has been assigned to trace out if any possibilities occur in the cadmium elevated women to form breast cancer.
Anti-proliferative effect of glycosides of Rivina humilis against HeLa cell lines
K. P. Indumathi, S. Velusamy 1
Department of Biochemistry, Kongu Arts and Science College, Erode, 1 Department of Genetic and Breeding, VCRI, Namakkal - 02, India
Aim of the study was to determine the anti-proliferative activities of Rivina humilis ethanol extract against HeLa cancer cell lines. The phytochemical constituents, anti-microbial, and anti-oxidant properties were analyzed. The plant exhibited anti-microbial activity and the zone of inhibition against staphylococcus, Pseudomonas, Serratia were 1.3 cm, 1.1 cm, 1.7 cm, respectively. The glycosides were purified by silica gel and sephadex G-100 column chromatography found to possess a molecular weight of 102 and 75 KDa. Its utility as a potent anti-cancer agents, crude and purified glycosides fraction were assessed for anti-proliferative action against normal and HeLa cell lines. It was observed that this plant exhibited more cytotoxic (154% decrease) in HeLa cell lines than that of normal HPLs by Tryptan blue cell exclusive assay, MTT assay, and neutral red assay, suggesting significant selective in inducing cytotoxicity. The genotoxicity imparted by the purified glycosides was less (14.28%) and 37.42% as an average by DNA fragmentation method and the comet scored was 276.8 pixels of DNA in tail. These data sustain that R. humilis has anti-cancer property and more studies are warranted on exploiting R. humilis as a potent anti-cancer drug.
Evaluation of anti-cancer properties of methanolic extract of Aristolochia indica, on cancerous albino rat
K. R. Udhayavani, M. Chandran
Department of Zoology, Thiagarajar College, Madurai - 625 009, India
Plants, which possess anti-cancer properties are subsequently been used as potent anti-cancer drugs. Aristolochia indica, an Indian medicinal plant, a twinning paleo herb, belongs to family Aristolochiaceae. It is used to treat cholera, leprosy, skin disease, menstrual problems, and snakebites. The plant is also used as antiseptic, anti-pyretic, and anti-fertility agent. The dry roots of A. indica, are reputedly used in Indian folk medicine. The essential oil of A. indica has been found to show anti-bacterial activity. An extract of A. indica showed tumor inhibitory activity against the adenocarcinoma. Sesquiterpenoid from the roots of A. indica exhibited the anti-cancer property. Hence, this study was designed to evaluate the anti-cancer properties of A. indica on cancerous albino rat.
Protective effect of fisetin on cell surface glycoconjugates during 7, 12-dimethylbenz (a) anthracene-induced hamster buccal pouch carcinogenesis
J. Sathiyapriya, K. Suresh
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamilnadu, India.
The protective effect of fisetin on cell surface glycoconjugates was investigated by measuring the status of protein bound hexose, hexosamine, total sialic acid, and fucose in the plasma, buccal mucosa, and erythrocyte membrane during 7,12, dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis. Oral squamous cell carcinoma was developed in the buccal pouch of male golden hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. The total numbers of tumors, tumor burden, and tumor volume were calculated in DMBA- and DMBA + fisetin-treated hamsters. We observed 100% of tumor formation with marked abnormalities in glycoconjugates in plasma, erythrocyte membrane, and buccal mucosa in tumor bearing hamsters. Oral administration of fisetin at a dose of 10 mg/kg bw to DMBA-treated hamsters on alternate days for 14 weeks reduced the tumor formation as well as protected the levels of glycoconjugates in DMBA-painted hamsters. This study thus suggests that fisetin has potent chemopreventive efficacy as well as protected abnormalities in cell surface glycoconjugates levels during DMBA-induced hamster buccal pouch carcinogenesis.
Modulating effect of 6 -paradol on histopathological alterations and apoptotic associated gene expression during 7,12-dimethylbenz(a)anthracene-induced oral carcinogenesis in male golden Syrian hamster
M. Arokia Vijayaanand, K. Suresh
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamilnadu, India
This study was designed to investigate the modulating effect of 6-paradol on histopathological alterations and immunoexpression pattern apoptotic-associated genes (P 53 , BCL-2, Caspase-3, and tumor necrosis factor-α [TNF-α]) during 7, 12-dimethylbenz[a] anthracene (DMBA)-induced oral carcinogenesis. Oral squamous cell carcinoma was induced in the buccal pouches of male Syrian golden hamsters by painting with 0.5% DMBA, three times a week for 14 weeks. To assess the chemopreventive potential of 6-paradol, a dose of 30 mg/kg b.wt was orally administrated to DMBA-treated hamsters on alternate days of DMBA painting for 14 weeks. The development of oral carcinoma was confirmed by histopathological analysis. We observed 100% tumor formation with altered expression pattern of apoptotic-associated genes in tumor bearing animals. Oral administration of 6-paradol reduced significantly DMBA-induced neoplastic changes (tumor incidence, tumor volume, and tumor burden) and histological abnormalities as well as modulated immunohistochemical expression pattern of P 53 , BCL-2, Caspase-3, and TNF-α toward the suppression of oral carcinogenesis. The results of this study confirmed that 6-paradol inhibited cellular proliferation and exhibited pro-apoptotic potential during DMBA-induced oral carcinogenesis.
Effect of rosmarinic acid on apoptotic and inflammatory proteins in 1,2-dimethylhydrazine-induced rat colon cancer
V. Karthikkumar, G. Sivagami, N. Nalini
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar - 608 002, Tamilnadu, India.
Colorectal cancer is one of the leading causes of cancer-related deaths in western countries and is becoming increasingly common in Asia. This study is an effort to unravel the anti-carcinogenic effects of rosmarinic acid (RA) in 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Male Wistar rats were divided into six groups and fed a high-fat diet. Group 1 served as control, group 2 was given RA (5 mg/kg b.w.) orally, every day for a total period of 30 weeks, and groups 3-6 were given weekly injections of DMH (20 mg/kg b.w. s.c.) once a week in the groin for the first 15 weeks. In addition to DMH, groups 4 - 6 received RA at the dose of 5 mg/kg b.w. during the initiation, post-initiation stages, and also throughout the entire study period. Macroscopic and microscopic tumors were identified in all the groups that received DMH. The results revealed that supplementation with RA significantly inhibited the formation ACF, ACF multiplicity, and tumors in DMH-treated rats. Moreover, RA supplementation to DMH-administered rats significantly reduced the cell proliferation markers viz., argyrophillic nucleolar organizing regions, proliferative cell nuclear antigen, and inflammatory markers COX-2. In addition to that, RA modulates the activities of apoptotic proteins caspases 3 and 9. The above findings clearly underline the chemopreventive efficacy of RA against DMH-induced colon carcinogenesis.
In vitro anti-tumorigenic effect of Ficus racemosa bark and isolation of lead anti-tumorigenic compounds by glide docking
A. Poongothai, S. Annapoorani
Department of Biochemistry, Biotechnology and Bioinformatics, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore - 43, India.
This study aimed to evaluate the in vitro anti-tumorigenic effect of Ficus racemosa bark against DLA tumor cells and also to isolate the lead anti-tumorigenic compounds by glide docking. The in vitro anti-tumorigenic effects of methanolic extract of F. racemosa bark were assessed by Trypan blue assay. The phytochemical constituents of methanolic extract of F. racemosa bark were identified by gas chromatography-mass spectroscopy (GC-MS) analysis and the in silico characterization of phytochemical constituents of the selected plants were carried out by standard precision (SP), extra precision (XP), and induced fit docking in order to identify the lead compounds responsible for the anti-tumorigenic activity. The results indicated that the extracts of the plant showed a dose-dependent cytotoxic activity to DLA tumor cells. GC-MS analysis showed the presence of total of 24 compounds. The SP docking followed by XP and induced fit docking confirmed the presence of two compounds from F. racemosa with high glide score and energy and ADME properties. These lead compounds can be recommended as anti-cancer agents.
Anti-tumorigenic efficacy of Morinda tinctoria and Nerium indicum leaves against DLA tumor implanted Swiss albino mice and in silico docking to identify the lead compounds
K. P. Sreena, S. Annapoorani
Department of Biochemistry, Biotechnology and Bioinformatics, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore - 43, India
This study was aimed to evaluate the anti-tumorigenic efficacy of methanolic extract of Morinda tinctoria (MEMT) and Nerium indicum (MENI) leaves against DLA implanted Swiss albino mice and also to identify the lead compound for anti-tumorigenic activity. The in vivo anti-tumorigenic effect was evaluated by assessing the activities of liver marker enzymes such as aspartate transaminase, alanine transaminase, and alkaline phosphatase in serum and activities of enzymatic anti-oxidants such as catalase, superoxide dismutase, and glutathione peroxidase and level of non-enzymatic anti-oxidants such as vitamin A, vitamin C, and vitamin E in the liver of DLA transplanted Swiss albino mice. The in silico docking studies were performed by standard precision and extra precision docking. The results indicated that activity of liver marker enzymes significantly increased and the activities of enzymatic and non-enzymatic anti-oxidants significantly decreased in DLA-induced mice. Administration of plant extracts individually and to the DLA-treated mice showed a significant decrease in the activities of liver marker enzymes and increase in the activities of enzymatic anti-oxidants and level of non-enzymatic anti-oxidants which proved their protective action against the damage caused by DLA tumor cells and maintains the normal function of the liver. These results also confirmed their anti-tumorigenic activity and in silico docking showed one lead compound in MENI and that can be recommended as anti-tumorigenic agent.
Oxidative stress markers
Department of Pharmacology, Meenakshi Ammal Dental College, Chennai, India
Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. In humans, oxidative stress is known to play an important role in the development of many diseases and ageing process or may exacerbate their symptoms. Reactive oxygen species (ROS) produced either endogenously or exogenously can attack lipid, protein, and nucleic acid simultaneously in the living cells. In nuclear and mitochondrial DNA, 8-hydroxydeoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, is formed when DNA is oxidatively damaged by ROS. It is the most frequently detected and studied DNA lesion. Upon DNA repair, 8-OHdG is excreted in the urine. Numerous evidences have indicated that urinary 8-OHdG not only is a biomarker of generalized, cellular oxidative stress but might also be a risk factor for cancer, atherosclerosis, and diabetes. For example, elevated level of urinary 8-OHdG has been detected in patients with various cancers. In human atherosclerotic plaques, there were increased amounts of oxidative modified DNA and 8-OHdG. The aim of these articles is to emphasize the availability and action of different types of oxidative stress markers.
Study of anti-oxidant status in myocardial infarction cases before and after thrombolytic therapy
P. T. Komala, K. Ambika Devi 1
Departments of Biochemistry Meenakshi Medical College, Kanchipuram, Tamil Nadu, 1 PIMS, Eluru, Vijayawada, Andhra Pradesh, India.
Free radical oxidative injury has been linked to various disorders including diabetes and myocardial infarction (MI). This study has been taken to analyze the extent of oxidative injury and the anti-oxidant defensive mechanism by estimating malonaldehyde and defensive markers such as serum ceruloplasmin, serum catalase, and serum uric acid at 6-12 h of onset of MI and 5 days after thrombolytic therapy. Out of total 100 cases, 50 age-matched control cases and 50 cases of known MI (with electrocardiogram report) were taken. Serum malonaldehyde was estimated by thiobarbituric acid method, serum ceruloplasmin by O-diansidine method, serum uric acid by uricase kit method, and serum catalase activity by spectrophotometric assay. Routine blood sugar, blood urea, serum creatinine, hemoglobin %, HIV, HBsAg were also done. The data were statistically analyzed and the mean, SD values are calculated. Student's ' t' test and ' P' values are also calculated. Statistically significant increase in malonaldehyde, uric acid, ceruloplasmin in MI cases compared to controls with " P" values <0.000 was seen. Significant decrease in serum catalase in control cases compared to patients with " P" value <0.000 was seen. There was a significant decrease in serum uric acid, malonaldehyde, and ceruloplasmin and increase in serum catalase after 5 days of thrombolytic therapy. The area under table of the ROC curves of different parameter was compared. In this study, there was significant increase in serum malonaldehyde, uric acid, and ceruloplasmin levels in MI cases compared to controls. Malonaldehyde is the best marker to indicate oxidative stress in MI, proved by area under curve (ROC curve) of the above parameters.
Phytochemical analysis and identification of flavonoids from Cardiospermum halicacabum by high performance lipid chromatography, gas chromatography mass spectroscopy, and Fourier transform infrared
R. Rajeswari, M. Sridevi
Department of Biochemistry, VMKV Medical College, Salem, Tamil Nadu, India.
Flavonoids are a group of polyphenolic compounds occur naturally in various parts of a plant and are an integral part of the human diet. They have been reported to exhibit a wide range of biological effects, including anti-bacterial, anti-viral, and anti-inflammatory actions. In addition, flavonoids inhibit lipid peroxidation (LPO), platelet aggregation, capillary permeability, etc. Cardiospermum halicacabum Linn. (Sapindaceae) is an herbaceous climber found throughout the plains of India, commonly used in the treatment of rheumatism, lumbago, earache, and fever. The plant possesses several flavonoids such as apigenin, pinitol, and luteolin. This study was undertaken to identify and confirm the presence of flavonoids in C. halicacabum leaf extracts. This study is to evaluate the presence of bioactive phytochemical constituents and identify flavonoids from C. halicacabum leaf extracts. Fresh leaves of C. halicacabum were collected, shade dried, and powdered. The coarse powder was subjected to successive extraction with petroleum ether, chloroform, acetone, and ethanol in Soxhlet apparatus. The crude extracts were subjected to preliminary phytochemical investigations and high performance lipid chromatography (HPLC), gas chromatography mass spectroscopy (GCMS), and Fourier transform infrared (FTIR) analyses. The bioactive phytochemical constituents such as alkaloids, tannins, flavonoids, and terpenoids are present in ethanolic extract of C. halicacabum. HPLC, GCMS, and FTIR analyses of ethanol extract of C. halicacabum show the presence of apigenin and luteolin. There is an increasing demand for herbal-based medicines as an alternative to modern medicines because of their toxicity and side effects on prolonged administration. This study confirms the presence of flavonoids in C. halicacabum leaf extract. Thus, this plant can be utilized as an alternative source of useful drugs. Isolation of flavonoids from ethanol extract of C. halicacabum leaf is in progress.
Protective effect of ethanolic extract of Hibiscus Rosa Sinensis petals in diabetic heart
Sneha S. Pillai, J. Saranya, S. Mini
Department of Biochemistry, University of Kerala, Thiruvananthapuram, Kerala, India.
Diabetes is one of the major risk factors for the development of cardiovascular diseases, accounting for 80% of all diabetic mortality. Major complications of diabetes that profoundly impact cardiac functions are glucotoxocity, lipotoxocity, and oxidative stress. Many of the oral anti-diabetic agents used today have serious adverse effects. Plant materials are considered one of the good sources for a lead to make new drug. Hibiscus rosasinensis (HRS) is an ornamental and medicinal plant found in India. This study evaluated the effect of ethanolic extract of HRS in streptozotocin (STZ)-induced diabetic rats and compared it with a standard anti-diabetic drug metformin. The extract and metformin were given intra-gastrically at a dose of 300 and 150 mg/kg body wt, respectively, for a period of 30 days. Increased levels of blood glucose, cholesterol, and triglycerides in diabetes were significantly decreased by extract administration. AST and ALT levels were normalized. The depleted anti-oxidant defense systems (catalase, superoxide dismutase, glutathione peroxidase, GRd, and glutathione-S-transferase) in the heart of diabetic rats were significantly enhanced and lipid peroxidation products (MDA, HP, and CD) were decreased by the extract supplementation. The overall effect was much better than metformin treatment. The histopathological studies of heart also reinforce our findings. Hence, this study reveals the cardioprotective effect of ethanolic extract of HRS in STZ-induced diabetes mellitus.
Night-time food restriction modulates the circadian patterns of redox status in rats
M. Jayakumar, P. Subramanian
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Tamil Nadu, India.
Temporal restricted feeding, a potent synchronizer of peripheral oscillators, has profound influences on light entrained rhythms through the suprachiasmatic nucleus, the master biological clock. This study is to investigate the effects of night-time food restriction (20:00-08:00 h) on the circadian rhythms of circulatory thiobarbituric acid reactive substances (TBARS), anti-oxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) in Wistar rats for 21 days. The experimental rats were grouped into normal and night-time food restricted. The variations of circadian characteristics (acrophase, amplitude, and mesor) of lipid peroxidation products and anti-oxidants were analyzed. Reduced lipid peroxidation (decreased mesor of TBARS) associated with increased anti-oxidant activities (increased mesor of SOD, CAT, GPx, and GST) and altered acrophase, amplitude, and 'r' values were found in night-time food restricted rats when compared to normal rats. These circadian alterations may be due to modulation in the temporal pattern of the endocrine profile, secretion of digestive enzymes, absorption of nutrients, and metabolism.
Oral anti-diabetic metformin protects hepatocytes against acetaminophen-induced oxidative damage and necrosis
R. Rajesh, B. T. Divya, S. Mini
Department of Biochemistry, Kerala University, Kariyavattom, Thiruvananthapuram - 695 581, India.
Glutathione depletion by N acetyl D benzoquinone imine (NAPQI), the active metabolite of acetaminophen prompts cells to undergo necrosis and apoptosis via oxidative damage leading to hepatotoxicity. Metformin, the oral anti-diabetic agent is gaining prior research significance due to its pleiotropic effect on different pathways such as AMPK, MAPK, and mTOR signaling, which shares events with metabolic activation and central propagation associated with DILI. A study was performed to evaluate the possible ameliorating effect of Metformin in oxidative stress produced by acetaminophen in cultured Chang liver cells. MTT assay and lactate dehydrogenase leakage assay show significant protective effect of Metformin at therapeutic doses. Increased viability confirms restoration of mitochondrial respiration since mitochondrial dysfunction is evident in AAP toxicity. Epifluorescent double staining with ETBr/Acridine orange confirms induction of apoptosis and necrosis in cultured hepatocytes which was significantly reversed by Metformin. Glutathione stimulating harmone depletion accounts for major reason in AAP toxicity and results show significant increase in cellular glutathione levels when treated with Metformin along with increase in glutathione reductase (40%). Our study shows significant ameliorative effect of Metformin on acetaminophen toxicity in cultured hepatocytes at therapeutic doses which confirm anti-oxidant effect of Metformin and the findings open new possibilities regarding therapeutic potential of Metformin.
Overweight adolescents and metabolic syndrome
Department of Biochemistry, BLDEU's Shri B M Patil Medical College, Bijapur - 586 103, Karnataka, India.
With the increasing prevalence and magnitude of adolescent obesity, the metabolic syndrome among the adolescents has been studied in many parts of India but not in northern Karnataka. Our study was aimed to examine the effect of varying degrees of adolescent obesity on the prevalence of metabolic syndrome. A total number of 200 adolescents, aged 14-19 years, were included in the study. Among 200 adolescents, 120 were overweight as defined by WHO and 80 were age- and sex-matched controls. In all the subjects, the height, weight, BMI, waist circumference, blood pressure, fasting serum glucose, total cholesterol, and triglycerides were measured by standard procedures. Socio-demographic data were collected by questionnaire. The metabolic syndrome was determined by the IDF consensus (2007) definition of metabolic syndrome in children and adolescents. Prevalence of metabolic syndrome was 20.2%, 12.4%, and 1.6% among adolescents who were overweight (basal metabolic index (BMI) >95 th percentile), at risk of overweight (BMI between 85 th and 95 th percentile), and normal weight (BMI below the 85 th percentile), respectively. Urban boys had the highest rate (5·8%) compared with girls and rural youngsters. A total of 76% of overweight adolescents had at least one and 38·1% overweight adolescents had at least two abnormalities of metabolic syndrome. We conclude that being overweight poses a greater risk of developing the metabolic syndrome among adolescents. Hence, primary prevention strategies are required to prevent further complications such as diabetes mellitus and its consequences.
Screening of mutations in Thiopurine-S-Methyl Transferase gene in Indian population for clinical action
N. Manoj Kumar, Anu Nandakumar, Sonam Chopra
Department of Genetic Engineering, SRM University, Chennai, India.
Cancer is the leading cause of death in the worldwide population. Chemotherapy is the basic treatment given for cancer patients which makes use of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathioprine. These drugs function as purine antagonists that inhibit the DNA synthesis. The incorporation of these drugs into DNA produces the required therapeutic effect, which creates enough toxicity to affect the cancerous cells. Thiopurine-S-Methyl Transferase (TPMT) enzyme is involved in eliminating the toxicity once the drug has produced its therapeutic effect and it starts getting accumulated in our body reaching to a toxic level. If the TPMT gene involved in producing this enzyme carries any mutation, it will lead to accumulation of toxicity produced by the drugs, which can cause severe myelo-suppression, anemia, leukopenia, and even death. Patients with such mutation suffering from cancer, if administered with thiopurine drugs, will be severely affected. In order to prevent such a case, the screening of such mutations is very much essential. Our work is basically to screen for the presence of mutations in TPMT gene in Indian population for clinical effect by genotyping. This will help the doctors in tailoring the dosage of thiopurine drugs from preventing the individuals with TPMT deficiency from various lethal therapeutic side effects and in future to administer them with alternative drugs in order to attain improved therapeutic effect.
Design, synthesis, characterization, and evaluation of DNA binding, cleavage activities of novel diketone-based macrocyclic complexes of Cu (II), Zn (II), and Ni (II)
S. Iyyam Pillai, S. Subramanian 1 , M. Kandaswamy
Departments of Inorganic Chemistry, and 1 Biochemistry, University of Madras, Guindy Campus, Chennai - 600 025, India.
Ever since the anti-cancer activity of cisplatin was discovered in 1965, novel strategies for the preparation of more effective less toxic, target specific and preferably non-covalently bonded metal complexes capable of cleaving the phosphodiester of the DNA continuous for the successful treatment of cancer. In this study, an attempt has been made to synthesize a series of macrocyclic mononuclear complexes of the type [M (C31H26N2O2) ClO4], where M = Cu (II), Ni (II), and Zn (II) by Schiff's base condensation of 1, 4 diamino butane and benzyl the ligand and the complexes have been characterized with the aid of FTIR, NMR, mass, elemental analysis, and electronic studies. Based on the data generated, a five coordinate square pyramidal geometry for all the synthesized complexes has been proposed. The interaction of the transition metal complexes with calf thymus DNA was studied by the use of physical methods such as ultra violet-visible, emission, and viscosity techniques. The intrinsic binding constants obtained through electronic absorption experiments and the electrophoretic mobility pattern during agarose gel electrophoresis established that the complexes were capable of cleaving SC plasmid DNA through oxidative stress.
Evaluation of DNA binding, cleavage activities of zinc flavonol complex
K. Vijayaraghavan, S. Iyyam Pillai 1 , S. Subramanian
Departments of Biochemistry, and 1 Inorganic Chemistry, University of Madras, Guindy Campus, Chennai - 600 025, India.
Cancer is a clinical syndrome that has tormented human throughout the history. DNA is generally the primary intra-cellular target of anti-cancer drugs because the interaction between small molecules and DNA can cause DNA damage in cancer cells, blocking the division of cancer cells, and resulting in cell death. Small molecules can interact with DNA through three non-covalent modes: Intercalation, groove binding, and external electrostatic effects. Among these interactions, intercalation is one of the most important DNA-binding modes, which is related to the anti-tumor activity of the compound. In this regard, mixed-ligand metal complexes were found to be particularly useful because of their potential to bind DNA via a multitude of interactions and to cleave the duplex by virtue of their intrinsic chemical, electrochemical, and photochemical reactivities. In this regard, binding of zinc complexes to DNA has attracted much attention. In this study, an attempt has been made to synthesize a zinc flavonol complex and evaluation of DNA binding and cleavage activities of the complex. The interaction of the zinc flavonol complex with calf thymus DNA was studied by the use of physical methods such as ultra violet-visible, emission, and viscosity techniques. The intrinsic binding constants obtained through electronic absorption experiments and the electrophoretic mobility pattern during agarose gel electrophoresis established that zinc flavonol complex was capable of cleaving DNA.
Docking, synthesis, and biological evaluation of some novel 5-substituted-1,3, 4-thiadiazol-2-amines and their schiff bases
Vachala Seekarajapuram Dinakaran, Bhargavi Bomma
Department of Pharmaceutical Chemistry, MCOPS, Manipal University, Manipal - 576 1 0 4, Karnataka, India.
An attempt was done to synthesize some novel 5-substituted-1,3,4-thiadiazol-2-amine derivatives by conventional method. Various aromatic acids were made to react with thiosemicarbazide and benzaldehyde, respectively. This method provides a simple and powerful tool for the synthesis of large number of multifunctional 1,3,4-thiadiazol-2-amines and they were evaluated for anti-oxidant, anti-inflammatory, and anti-cancer activities. Out of all the 10 synthesized compounds, 5-chloro-2-hydroxy substituted phenyl at the 5 th position of the 1,3,4-thiadiazol-2-amine (TDZS-4) showed potent anti-oxidant activity by DPPH radical scavenging method at low concentration with IC 50 value 16.2 μg/mL. The same compound, TDZS-4 had shown significant reduction in inflammation at both 1 st and 3 rd h with % reduction in edema of 100 and 85%, respectively. All the synthesized compounds were subjected to docking interaction with the 2CIB protein in order to determine their in silico effect on cancer, and the results revealed that the TDZS-1 and TDZS-2 bearing 4-hydroxy-3-nitro and 4-methoxy-3-nitro substituted phenyl at the 5 th position of the 1,3,4-thiadiazol-2-amine, respectively, have shown better Moldock score values indicating their better interaction with 2CIB protein. Compounds showing well-docked configuration with 2CIB had also shown better in vitro cytotoxicity when evaluated on Hep2 cell lines. Further, the in vivo study by EAC model revealed that the compound TDZS-1 was effective in animals as well, endorsing the importance of TDZS-1 compound as an anti-cancer agent.
Screening of anti-diarrheal and phytochemical potential of Aeglemarmelos Corr.
S. Balamurugan, G. Thiyagarajan, S. Karthikeyan, S. Selvamani
Department of Botany, Wing (DDE), Annamalai University, Annamalainagar - 608 002, India.
Medicinal plants are playing a vital role in human health care. About 80% of the world populations relying on traditional medicine for their primary health care. Medicinal plants are the backbone of traditional system of medicine such as Siddha, Ayurvedha, etc. Traditional system of medicine always plays an important role to treat different sorts of diseases including diabetes and cancer. In this series, Aeglemarmelos raw fruit pulp acts as curative agent and it worked against diarrhea, ulcer healing, diabetes, oxidative stress, and other biological activities. To understand the anti-diarrheal effect of Aeglemarmelos fruit pulp, this work was undertaken. This work was carried out for the period of 5 months. Aeglemarmelos fresh fruit pulp was collected from the trees of Annamalainagar, and processed using standard methodologies adopted from Ayurvedha pharmacopoeia of India. The plant material was authenticated and processed. Extract was prepared using aqueous and alcohol. Intestinal mobility and fecal score methods were employed to screen anti-diarrheal activity. Results revealed that the extract was effective in controlling diarrhea.
Anti-oxidant and anti-microbial activities of Morinda citrifolia fruit
S. Vennila, D. Brindha
Department of Biochemistry, PSG College of Arts and Science, Coimbatore - 14, India.
Medicinal plants have been used for centuries as remedies for human diseases because they contain components of therapeutic value. One such important fruit is Morinda citrifolia L, a member of the family Rubiaceae, which is commonly known as Noni and is used in traditional medicine as a remedy for various diseases. The 50% ethanolic extract of the fruit was found to contain highest amount of enzymatic (SOD, CAT, peroxidase, glutathione peroxidase, glutathione reductase, and glutathione-s-transferase) anti-oxidant activity. The 50% ethanolic extract of M. citrifolia was screened for their anti-microbial activity using disc diffusion method. The anti-bacterial activity of 50% ethanolic extract of M. citrifolia at a concentration of 100 μg against Klebsiella pneumoniae was found to be more effective than all the organisms which were compared to the standard drug Ciprofloxacin (5 μg/ml). The anti-fungal activity of 50% ethanolic extract of M. citrifolia at a concentration of 100 μg against Aspergillus fumigatus was found to be more effective than all the organisms which were compared to the standard drug Fluconazole (20 μg/ml). In minimum inhibitory concentration, when the concentration was increased, the growth inhibition was decreased in all the organisms. From this study, it could be concluded that, the phytochemicals from the fruit of M. citrifolia were proved to be potent anti-oxidant and anti-microbial agents.
Ameliorating effect of aqueous extract of lettuce (Lactuca sativa) fed with selenate against oxidative stress and apoptotic or necrotic cell death of albino Wistar rats
Iafshana Shafi, S. Milton Prabu
Department of Zoology, Annamalai University, Annamalai Nagar - 608 002, India.
Leaves of the lettuce plant are often used by man as food supplement because of the nutritional as well as high mineral potentials of the plant. The plant has been reported to have an excellent composition of calcium and iron; good source of vitamins A, B, and C, with a very high roughage value. The aim of this study was to elucidate the effect of aqueous leaf extract of lettuce on the oxidative stress and apoptosis on the kidney and liver of Wistar albino rat. Thirty-two adult Wistar albino rats of both sexes were used for this study. They were assigned into three extract treated groups and were administered with 300 mg/kg, 200 mg/kg, and 100 mg/kg body weight of the extract, respectively, and one control group, administered with equal volume of normal saline. Administration was done orally using an orogastric tube for 2 weeks. Twenty-four hours after the last administration, all the animals were sacrificed using cervical dislocation, laparatomy was performed, the kidney and liver were excised, trimmed free of fat, rinsed in cold phosphate buffer solution solution. The liver was quickly fixed in 10% formol saline, while the kidney was fixed in Bouin's fluid. In the kidneys, there were neither tubular necroses nor interstitial and glomerular hemorrhage. Both the distal and proximal convoluted tubules were free of occlusion. The glomeruli were also devoid of distortion, derangement, and degenerative changes. The histology of the liver displayed normal parenchymal architecture with cords of hepatocytes and portal tracts when treated with the extract. The central veins were well preserved. There was no ballooning degeneration of the hepatocytes, necrosis, or formation of mallory bodies. The sinusoids were also devoid of congestion and there were no cytoplasmic vacuolations of the hepatocytes. These findings suggest that the consumption of lettuce has no deleterious implications on the histological profile of the kidney and liver of Wistar albino rats.
Screening of anti-diarrheal potential of Hemidesmus indicus (L) R. Br leaves
Department of Botany Wing (DDE), Annamalai University, Annamalainagar - 608 002, India.
Medicinal plants are the backbone of traditional system of medicines such as Siddha, Ayurveda, etc. The acceptance of traditional medicine as an alternative form of health care and development of microbial resistance to the available antibiotics has led researchers to investigate the anti-microbial activity of medicinal plants. Traditional system of medicines always plays an important role to treat different sorts of diseases. In this series, leaves of Hemidesmus indicus L. are used to treat diarrhea. This study was planned to analyze the leaves of H. indicus for its anti-diarrheal potentials. Infusions of the leaves of the plant are variously utilized as medications for treating diarrhea. H. indicus leaves were dried under shade and extracted. Anti-diarrheal study results revealed that both extracts were found to possess anti-diarrheal activity. Extracts were significantly reduced intestinal mobility. The present findings suggest that H. indicus could be a potential source of natural anti-diarrheal agent.
Wound healing activity of a polyherbal Siddha formulation
R. Sridhar, M. Srinivasan
Medicinal Chemistry and Nanoscience Research Laboratory, Centre for Research and Development, East Campus, PRIST University, Thanjavur - 614 904, Tamilnadu, India.
Non-healing wounds are a significant problem in healthcare systems all over the world. Unlike other areas of health care, wound management needs much attention for maximum benefit. During the last 1 0 years, different types of multidisciplinary concepts for the treatment of wounds have been created. A number of drugs ranging from simple non-expensive analgesics to complex and expensive chemotherapeutic agents administered in the management of wound. These drugs do not play a major role in the wound healing process. The production and clinical evaluation of herbal remedies have made revolution in the use of traditional medicine in modern industrial venture rather than the use of raw herbal materials. On this basis, medicated oil prepared by the Siddha medicine system was selected and subjected for this experiment. Excision wound model was used to evaluate the wound healing activity using rats. Medicated oil was applied on the wound surface and the rate of wound healing was studied by taking photographs of wound surface on regular intervals. These wound surface images were measured and calculated using a software UTHSCSA image tool. Results showed that the wound healing activity of medicated oils prepared by the Siddha medicine was significant (P < 0.05) than the control.
Preparation and evaluation of curcumin nanosuspension for therapeutic application
P. F. Steffi, M. Srinivasan
Medicinal Chemistry and Nanoscience Research Laboratory, Centre for Research and Development, East Campus, PRIST University, Thanjavur - 614 904, Tamilnadu, India.
Curcumin is a natural product found in the rhizome of Curcuma longa being responsible for its biological actions. The medicinal use of this plant has been documented in Ayurveda system of medicine for over 6000 years. It is commonly used as a spice, flavoring agent, food preservative, and coloring agent for decoration. It exhibits anti-inflammatory, anti-viral, anti-bacterial, anti-oxidant, and nematocidal activities. Due to its poor solubility in water, there is a need to formulate this curcumin for better bioavailability. An experiment was planned to formulate the curcumin to nanosuspension for therapeutic application. Curcumin was extracted by acetone using soxhlet apparatus and evaporated by vacuum rotary evaporator. It was recrystallized by saturation solubility method using different solvent system. The crystals obtained from evaporation were subjected for characteristic analysis such as physical parameter like melting point and solubility then by instrumentations such as thin layer chromatography and UV-VIS spectrophotometer to find out the presence and purity of curcumin. Nanosuspension was prepared by bottom up method using saturation solubility method using acetone and water solvent system with SDS stabilizer. The stability of this formulation was characterized by the measurement of zeta potential. Results showed that prepared nanosuspension has good stability (-28.9 ± 245 mV) up to 15 days from the day of preparation.
Cancer and smoking
B. Bhat, R. S. Jayasomu
CSIR-National Institute of Science Communication and Information Resources (NISCAIR), New Delhi, India.
Cancer is one of most challenging non-communicable diseases (NCD) that haunt humankind and can be referred "life-threatening" due to their epidemic nature and the extent of mortality and morbidity they cause. Cancer in fact, is not a single disease but a generic term for a spectrum of biologically different conditions. Cancer burden in Tamil Nadu for 2012-2016 has been predicted at an alarming level of 55,000 new cases per year. Although breast cancer replaced cervical in the number of cases, particularly in urban areas, lung, stomach, and large bowel cancers have also shown an increasing trend. Experts suggest that cancer should be declared as a "notifiable disease" in order to prevent the epidemics of tobacco-related cancers as well as challenges of ominous cancer such as lung and stomach cancers. Smoking is by far the most important preventable cause of cancer in the world. Smoking accounts for one in four UK cancer deaths, and nearly a fifth of all cancer cases. In the UK, smoking kills five times more people than road accidents, overdoses, murder, suicide, and human immune deficiency virus all put together. Smoking causes more than four in five cases of lung cancer. Lung cancer has one of the lowest survival rates of all cancers, and the good news is that most of these deaths are preventable, by giving up smoking in time. Smoking also increases the risk of over a dozen other cancers including cancers of the mouth, larynx (voice box), pharynx (upper throat), nose and sinuses, esophagus (food pipe), liver, pancreas, stomach, kidney, bladder, cervix, and bowel, as well as one type of ovarian cancer and some types of leukemia. There is also some evidence that smoking could increase the risk of breast cancer. Strict smoking policies thus help reducing smoking rate considerably and thereby save vital number of lives.
Chemopreventive efficacy of lupeol during 7, 12-dimethylbenz(a)anthracene-induced oral carcinogenesis
D. Palanimuthu, S. Manoharan
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar - 608 002, Tamil Nadu, India.
The chemopreventive potential of lupeol was assessed by monitoring the tumor incidence and using the status of phase I and II xenobiotic metabolizing enzymes, lipid peroxidation, and anti-oxidants as biochemical end points during 7,12-dimethylbenz(a) anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumors were developed in the buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA three times a week for 14 weeks. Oral squamous cell carcinoma with marked abnormalities in the status of biochemical markers was noticed in hamsters treated with DMBA alone. Oral administration of lupeol at a dose of 50 mg/kg bw completely inhibited the formation of oral tumors and brought back the status of biochemical markers during DMBA-induced oral carcinogenesis. This study thus demonstrates the chemopreventive potential of lupeol in DMBA-induced oral carcinogenesis.
Chemopreventive efficacy of citral in 7,12- dimethylbenz (a) anthracene (DMBA)-induced hamster buccal pouch carcinogenesis
D. Rajasekaran, Shanmugam Manoharan
Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar - 608 002, Tamil Nadu, India
Our aim was to investigate the chemopreventive efficacy of citral in 7,12-dimethylbenz (a) anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral tumor was developed in the hamster buccal pouches by painting with 0.5% DMBA in liquid paraffin three times weekly for 14 weeks. We observed 100% tumor formation with marked abnormalities in the status of phase I and II detoxification agents, lipid peroxidation by-products, and anti-oxidants in hamsters treated with DMBA. Oral administration of citral at a dose of 100 mg/kg bw to DMBA-treated hamsters completely prevented the tumor formation as well as brought back the status of above-mentioned biochemical variables. The results thus indicate that citral has significant chemopreventive potential, which is probably due to its anti-oxidant potential as well as modulating effect on the activities of phase I and II detoxification enzymes during DMBA-induced oral carcinogensis.
Anti-diabetic effect of Salacia oblonga hydroalcoholic extract on streptozotocin-induced diabetic rats
N. Medhavi, S. Manoharan 1 , M. Srinivasan
Centre for Research and Development, PRIST University, Thanajavur - 613 403, 1 Department of Biochemistry and Biotechnology, Annamalai University, Chidambaram, Tamilnadu, India.
Acarbose is a carbohydrate found in the hydroalcoholic extract of Salacia oblonga, which is being used by traditional medicine practitioners for treating diabetes. Recent studies proved that the Acarbose is one of the compounds responsible for this anti-diabetic activity. This study has investigated the anti-hyperglycemic effect of Salacia oblonga hydroalcoholic extract (water/alcohol 60:40%) by measuring the level of blood glucose, and glycosylated hemoglobin parameters in the blood of streptozotocin-induced diabetic rats. An increase (P < 0.05), in blood glucose and glycosylated hemoglobin, was noticed in diabetic animals as compared to normal rats. On treatment with Salacia oblonga hydroalcoholic extract at a dose of 50 mg/kg p.o for the period of 30 days, all these values of induced animals came to the normal. It is concluded that oral administration of Salacia oblonga hydroalcoholic extract demonstrated the anti-diabetic effect in streptozotocin-induced diabetic rats.
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