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ORIGINAL ARTICLE
Year : 2022  |  Volume : 12  |  Issue : 4  |  Page : 275-281

Actions of Caffeic Acid Loaded-Silver Nanoparticles on Blood Pressure, Oxidative Stress, and Antioxidants in Nitric Oxide Deficient Hypertensive Rats


Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India

Date of Submission16-Jun-2022
Date of Decision03-Jul-2022
Date of Acceptance18-Aug-2022
Date of Web Publication30-Nov-2022

Correspondence Address:
MSc, PhD Boobalan Raja
Associate Professor, Department of Biochemistry & Biotechnology, Annamalai University, Annnamalainagar-608 002, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijnpnd.ijnpnd_41_22

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   Abstract 


Objectives: This study aimed to evaluate the antihypertensive and antioxidant potential of caffeic acid-loaded silver nanoparticles (CA-AgNPs) in Nω −Nitro-L-arginine methyl ester hydrochloride (L-NAME) induced hypertension in male albino Wistar rats. Materials and methods: The rats have randomly divided into four groups, that is, Group I Control rats, Group II rats injected with CA-AgNPs, Group III L-NAME rats, and Group IV −L-NAME+ CA-AgNPs. Hypertension was induced in rats by oral administration of L-NAME (40 mg/kg body weight) dissolved in drinking water daily for 4 weeks. Rats were given intraperitoneal injection of CA-AgNPs (0.5 mg/kg/ml). Results: The results showed that L-NAME administration caused a sustained increase in blood pressure, levels of thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), and a significant decrease in the activities of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx), and levels of non-enzymatic antioxidants such as vitamin C and vitamin E in the tissues such as heart, aorta, liver, and kidney. Above pathological changes were considerably restored with the treatment of CA-AgNPs. Conclusions: The result confirms CA-AgNPs have enough potential to narrow down hypertension and oxidative stress in L-NAME hypertensive rats.

Keywords: Caffeic acid, hypertension, oxidative stress, antioxidants, silver nanoparticles


How to cite this article:
Kalaiarasi K, Raja B, Saranya D, Dhakshinamoorthi R. Actions of Caffeic Acid Loaded-Silver Nanoparticles on Blood Pressure, Oxidative Stress, and Antioxidants in Nitric Oxide Deficient Hypertensive Rats. Int J Nutr Pharmacol Neurol Dis 2022;12:275-81

How to cite this URL:
Kalaiarasi K, Raja B, Saranya D, Dhakshinamoorthi R. Actions of Caffeic Acid Loaded-Silver Nanoparticles on Blood Pressure, Oxidative Stress, and Antioxidants in Nitric Oxide Deficient Hypertensive Rats. Int J Nutr Pharmacol Neurol Dis [serial online] 2022 [cited 2023 Jan 26];12:275-81. Available from: https://www.ijnpnd.com/text.asp?2022/12/4/275/362413




   Introduction Top


Cardiovascular diseases (CVDs) are the major cause of morbidity and mortality in developed and developing countries. Hypertension is a crucial risk factor for CVDs and contributes to one-third of global mortality.[1],[2] Hypertension, a worldwide epidemic at present, is not a disease in itself rather it is an important risk factor for serious cardiovascular disorders including myocardial infarction, stroke, heart failure, and peripheral artery disease.

It is well-established that oxidative stress contributes to the development of hypertension through nitric oxide (NO) deficiency.[3],[4],[5] The vascular endothelial cells product NO is a potent vasodilator with important role in the growth and resistance of blood vessels.[6],[7],[8] NO synthase inhibitors induce endothelial dysfunction and oxidative stress by decreasing NO activity.[9] Subchronic administration of laboratory rodents with NO synthase inhibitors, such as N-nitro-L-arginine methyl ester (L-NAME), results in chronic hypertension,[10],[11] hence the common use of this chemical for developing hypertension in experimental models.

Phenolic acids are predominantly spread-out in food sources like nuts, grains, and beverages. Caffeic acid (CA) is a hydroxycinnamic acid that belongs to the phenolic acid family of polyphenols. It is the main hydroxycinnamic acid present in the human diet, with the highest content being found in blueberries, kiwis, plums, cherries, and apples, although also present in cereals, carrots, salad, eggplants, cabbage, artichoke, and coffee.[12],[13],[14] CA shows promising antihypertensive and antioxidant activities, and might possess favorable effects both in in vitro and in vivo model.[15],[16],[17],[18] Its antioxidant ability is a major mechanism via which it functions ([Figure 1]).[19] The molecular structure of caffeic acid possesses a cathecol group with an α,β-unsaturated carboxylic acid chain. It can be expressed in duo ways; as a primary antioxidant which prevents the production of free radicals[20] and as a secondary antioxidant by forming complexes with metals thus inhibiting peroxides decomposition, thus decreasing the production of free radicals and their attack on lipids, double bonding affinity of polyunsaturated fatty acids, bases of DNA, and amino acids of proteins.[21]
Figure 1 Structure of caffeic acid.

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Though numerous drugs acting via different mechanism of action are available in the market as conventional formulations for the treatment of hypertension but they face substantial challenges regarding their bioavailability, dosing, and associated adverse effects which greatly limit their therapeutic efficacies. Various studies have demonstrated that nanocarriers can significantly increase the drug bioavailability thereby reducing the frequency of dosing in addition to minimizing toxicity associated with a high dose of the drug. Nanoparticles seem to be the better approach to removing the constraints related to oral delivery of antihypertensive. Different nanoparticulate systems like polymeric nanoparticles and lipid-based nanoparticles (nanoemulsion, SLN, NLC, lipotomes) have been studied to overcome limitations associated with the oral delivery of antihypertensive. In this background this study was designed to determine the antihypertensive and antioxidant potential of caffeic acid-loaded silver nanoparticle (CA-AgNPs) in L-NAME-induced hypertension in male Albino Wistar rats.


   Materials and methods Top


Animals

Adult male albino Wistar rats of 8 weeks old (150–220 g) were purchased from Nandha College of Pharmacy, Erode, Tamil Nadu, India. Animals were kept in a polypropylene cage by given a standard pellet diet and water in ad libitum. They were maintained in an air-conditioned room with a 12 h light/12 h dark cycle. The experimental process was carried out with the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals, New Delhi, India and approved by the Animal Ethical Committee of Nandha College of pharmacy (Reg No.688/PO/Re/S/02/CPCSEA, Pro. No.NCP/IAEC/2021-22/26).

Drugs and chemicals

Caffeic acid, silver nitrate, and Nω −Nitro-L-arginine methyl ester hydrochloride (L-NAME) were purchased from Sigma-Aldrich Company (St. Louis, Missouri, USA). All other chemicals used for studies were of analytical grade obtained from E. Merck, Mumbai and HIMEDIA, Mumbai, India.

Synthesis of caffeic acid-loaded silver nanoparticles (CA-AgNPs)

About 5 mL of caffeic acid (20 mM) was added to a 5 mL of 2 × 10−3 M of AgNO3 and the reaction mixture was stirred for about 20 min at room temperature conditions. The change in the color of the solution from colorless to brown indicated the formation of silver nanoparticles.[22]

L-NAME-induced hypertensive animal model and CA-AgNPs treatment

To induce hypertension, rats were given L-NAME in drinking water at a dosage of 40 mg/kg b.w. for 4 weeks.[23],[24]. CA-AgNPs (0.5 mg/kg/ml) was given intraperitoneal injection every day for a period of consecutive 4 weeks.[25],[26],[27]

Experimental protocol

Each of the following groups consisted of six animals. Group I: Control; Group II: rats were treated with CA-AgNPs (0.5 mg/kg b.w.)[25]; Group III: rats were given

L-NAME (40 mg/kg b.w.); Group IV: rats were co-administered with L-NAME (40 mg/kg b.w.) and CA-AgNPs (0.5 mg/kg/ml). After the completion of the experimental period, the rats were anesthetized and sacrificed by cervical dislocation. Tissues such as heart, aorta, kidney, and liver were surgically removed, washed with cold physiological saline, cleared off adherent lipids, and immediately transferred to ice-cold containers.

Blood pressure measurement

Before the commencement of the experiment, animals were trained with the instrument for measuring blood pressure. In all groups of animals, mean arterial pressure was measured every week during the entire period of the study noninvasively using a tail-cuff method (IITC, model 31, USA) according to standard procedures. Values reported are the average of three readings. All the recordings and data analyses were done using a computerized data acquisition system and software.

Lipid peroxidation products and antioxidants

The levels of thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LOOH) in tissues (liver, heart, aorta, and kidney) were estimated by the methods of Niehaus and Samuelsson[28] and Jiang et al.[29] respectively. The activities of enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in tissues were estimated by the methods,[30],[31],[32] respectively. The levels of non-enzymatic antioxidants such as vitamin C and vitamin E in tissues were estimated by the methods,[33],[34],[35] respectively.

Statistical analysis

Data were analyzed by one-way analysis of variance followed by Duncan’s multiple range tests using a statistical package for the social science software version 20.0. “IBM SPSS Statistics for Windows, version 20 (IBM Corp., Armonk, New York, USA).” Values are represented as mean ± S.D. for six rats in each group. Values were considered significant when P < 0.05.


   Results Top


[Figure 2] and [Figure 3] show the effect of CA-AgNPs on systolic and diastolic blood pressure in control and L-NAME-induced hypertensive rats for 4 weeks. The systolic and diastolic blood pressures were found to be significantly higher (P < 0.05) in L-NAME-induced hypertensive rats (group III). Treatment with CA-AgNPs significantly (P < 0.05) reduced the systolic and diastolic blood pressure in L-NAME-induced hypertensive group (group IV). There is no significant variation between groups I and II.
Figure 2 Effect of CA-AgNPs on systolic blood pressure (SBP) in control and L-NAME-induced hypertensive rats. Columns are mean ± S.D. for six rats in each group. Data were analyzed by one-way ANOVA followed by Duncan’s multiple range test (DMRT). **Correspondence to P < 0.05 compared with the control. #P < 0.05 compared with the L-NAME.

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Figure 3 Effect of CA-AgNPs on diastolic blood pressure (DBP) in control and L-NAME-induced hypertensive rats. Columns are mean ± S.D. for six rats in each group. Data were analyzed by one-way ANOVA followed by Duncan’s multiple range test (DMRT).***Correspondence to P < 0.05 compared with the control. #P < 0.05 compared with the L-NAME.

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The values of TBARS, LOOH in tissues are given in [Table 1]. TBARS, LOOH values in liver, heart, kidney, and aorta of L-NAME-induced hypertensive rats (group III) were significantly higher when compared with those of control rats (group I) (P < 0.05). Treatment with CA-AgNPs to rats with L-NAME-induced hypertension (group IV) reduced the TBARS, LOOH values significantly compared with L-NAME-induced hypertension (group III) ([Table 1]).
Table 1 Effect of CA-AgNPs on lipid peroxidation markers

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The activities of SOD, CAT, and GPx in tissues (liver, kidney, heart, and aorta) of control and L-NAME hypertensive rats are presented in [Table 2]. The activities of these enzymatic antioxidants were significantly (P < 0.05) decreased in L-NAME-induced hypertensive rats (group III). Treatment with CA-AgNPs significantly (P < 0.0.5) restored the activity of these enzymatic antioxidants in tissues (group IV). SOD, CAT, and GPx values have no alteration in treatment with CA-AgNPs in control rats (group II) compared with the control rats (group I).
Table 2 Effect of CA-AgNPs on enzymatic antioxidants

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[Table 3] illustrates the levels of non-enzymatic antioxidants such as vitamin C and vitamin E in tissues. Their levels were significantly decreased in L-NAME-induced hypertensive rats (group III) compared with the control rats (group I). Administration of CA-AgNPs to L-NAME-induced hypertensive rats (group IV) significantly improved the levels of vitamin C and E compared with untreated rats (group III). Vitamin C and E levels did not alter significantly on treatment with CA-AgNPs of rats (group II) compared with normal control rats (group I).
Table 3 Effect of CA-AgNPs on non-enzymic antioxidants

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   Discussion Top


Chronic blockade of nitric oxide (NO) synthesis by L-NAME-mediated nitric oxide synthase (NOS) inhibition is a well-known model of hypertension. Although this model cannot be easily extrapolated to human hypertension conditions, it provides the possibility of reducing the causes of increased blood pressure to a single factor, which is a decrease in NO bioavailability. Sufficient NO is associated with normal vasodilation and, consequently, normal blood pressure.[36] Thus, a failure to generate NO or an enhanced NO consumption can lead to hypertension. We confirmed that chronic administration of L-NAME leads to a marked elevation in blood pressure as well as a CA-AgNPs preventing effect in animals.

Though numerous drugs acting via different mechanisms of action are available in the market as conventional formulations for the treatment of hypertension but they face substantial challenges regarding their bioavailability, dosing, and associated adverse effects which greatly limit their therapeutic efficacies. Various studies have demonstrated that nanocarriers can significantly increase the drug bioavailability thereby reducing the frequency of dosing in addition to minimizing toxicity associated with a high dose of the drug. Caffeic acid (CA) is a naturally occurring hydroxycinnamic acid with an interesting array of biological activities; for example, antioxidant, anti-inflammatory, antimicrobial, and cytostatic. More recently, several synthetic analogs have also shown similar properties, and some with the advantage of added stability. The significant reduction in blood pressure in our study is correlated with previous studies that show that CA, exhibit vasorelaxant activity by acting on the endothelial and vascular smooth muscle cells. Vasorelaxant mechanisms include the increased endothelial NO secretion, modulation of calcium and potassium channels, and modulation of adrenergic receptors. Together with a negative chronotropic effect, vasorelaxant activity contributes to lower blood pressure, as several preclinical studies show. Their antioxidant, anti-inflammatory, and anti-angiogenic properties contribute to an important anti-atherosclerotic effect, and protect tissues against ischemia/reperfusion injuries and the cellular dysfunction caused by different physico-chemical agents.[37]

Oxidative stress performs a critical function in the progression of hypertension, which in turn, promotes the generation of free radicals and oxidative damages to multiple organs especially the heart, which results in a decrease cell membrane fluidity.[38],[39] Oxidative stress damage biological molecules by increasing the large amount of ROS.[40] Bioavailability of ROS has a major impact on cardiovascular disease associated with hypertension. The ROS production, superoxide anion, hydrogen peroxide, and lipid peroxides levels were reported to increase in L-NAME-induced hypertensive rats, due to a decrease in enzymatic and non-enzymatic antioxidants.[38],[39],[41]

Our findings also confirmed that CA-AgNO3 loaded nanoparticles significantly reduced the lipid peroxidation markers such as TBARS, LOOH, and increased the activity and levels of enzymatic and non-enzymatic antioxidants. The antioxidant activity of CA, at least in cellular systems in vitro, the closest to in vivo conditions, is dependent not only on the molecular structure, but also on the solubility, hydrophobicity, and stability of the compounds.[42] CA is able to scavenge both reactive oxygen and nitrogen species, in acellular and in cellular systems.[43],[44] CA prevents the chain initiation of lipid peroxidation by scavenging peroxyl radical (LOO).[45] CA has also been shown to maintain proteins against oxidation by scavenging ROS and by assisting in their repair through transfer of electrons to amino acid radicals.[46] Finally, antioxidant and free radical scavenging activities are attributed to several functional groups in the CA molecular structure, with the ortho-dihydroxyl functionality in the catechol ring being probably the best studied so far.[47],[48],[49],[50]


   Conclusion Top


New generation antihypertensive drugs, new novel molecular targets, and nanotechnology-based delivery systems are currently in the pivotal stage of preclinical trial and clinical trial and are showing positive results. Nanotechnology is a promising approach to resolving several constraints of antihypertensive. The targeted nanoparticles can effectively take antihypertensive to its site of action whether it is the kidney, heart, or smooth muscle. The result from our study confirms CA-AgNPs have enough potential to narrow down hypertension and oxidative stress in L-NAME-induced hypertensive rats. However, further studies will be necessary to deepen the unique properties of this new formulation, thus providing the basis for new therapeutic strategies in this type of hypertension.

Acknowledgements

The authors acknowledge the support from Dr S.K. Siva Kumar, Associate Professor, Department of Physics, Faculty of Science, Annamalai University for his support in the synthesis and characterization of CA-AgNO3 nanoparticles.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Roth GA, Mensah GA, Johnson CO et al. Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study. J Am Coll Cardiol. 2020;76:2982–3021.  Back to cited text no. 1
    
2.
Wu CY, Hu HY, Chou YJ, Huang N, Chou YC, Li CP. High blood pressure and all-cause and cardiovascular disease mortalities in community-dwelling older adults. Medicine (Baltimore) 2015;94:2e2160.  Back to cited text no. 2
    
3.
Förstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res 2017;120:713-35.  Back to cited text no. 3
    
4.
Baradaran A, Nasri H, Rafieian-Kopaei M. Oxidative stress and hypertension: possibility of hypertension therapy with antioxidants. J Res Med Sci 2014;19:358.  Back to cited text no. 4
    
5.
Schulz E, Jansen T, Wenzel P, Daiber A, Münzel T. Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension. Antioxid Redox Signal 2008;10:1115-26.  Back to cited text no. 5
    
6.
Rajendran P, Rengarajan T, Thangavel J et al. The vascular endothelium and human diseases. Int J Biol Sci 2013;9:1057.  Back to cited text no. 6
    
7.
Sandoo A, Van Zanten JJ, Metsios GS, Carroll D, Kitas GD. The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J 2010;4:302.  Back to cited text no. 7
    
8.
Zou MH, Cohen RA, Ullrich V. Peroxynitrite and vascular endothelial dysfunction in diabetes mellitus. Endothelium 2004;11:89-97.  Back to cited text no. 8
    
9.
Kumar MS, Kumar S, Raja B. Antihypertensive and antioxidant potential of borneol-a natural terpene in L-NAME-induced hypertensive rats. Int J Pharm Biol Arch 2010;1:271-9.  Back to cited text no. 9
    
10.
Aydogdu N, Yavuz OY, Taştekin E, Tayfur P, Kaya O, Kandemir N. The effects of irisin on nω-nitro-L-arginine methyl ester hydrochloride-induced hypertension in rats. Balkan Med J 2019;36:337.  Back to cited text no. 10
    
11.
Kopincova J, Puzserova A, Bernatova I. L-NAME in the cardiovascular system—nitric oxide synthase activator? Pharmacol Rep 2012;64:511-20.  Back to cited text no. 11
    
12.
El-Seedi HR, El-Said AM, Khalifa SA et al. Biosynthesis, natural sources, dietary intake, pharmacokinetic properties, and biological activities of hydroxycinnamic acids. J Agric Food Chem 2012;60:10877-95.  Back to cited text no. 12
    
13.
Del Rio D, Rodriguez-Mateos A, Spencer JP, Tognolini M, Borges G, Crozier A. Dietary (poly) phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal 2013;18:1818-92.  Back to cited text no. 13
    
14.
Sova M, Saso L. Natural sources, pharmacokinetics, biological activities and health benefits of hydroxycinnamic acids and their metabolites. Nutrients 2020;8:2190.  Back to cited text no. 14
    
15.
Hiemori-Kondo M, Nii M. In vitro and in vivo evaluation of antioxidant activity of Petasites japonicus Maxim. flower buds extracts. Biosci Biotechnol Biochem 2020;84:621-32.  Back to cited text no. 15
    
16.
Laranjinha J. Redox cycles of caffeic acid with α-tocopherol and ascorbate. Methods Enzymol 2001;335:282-95.  Back to cited text no. 16
    
17.
Lukitaningsih E, Nurrulhidayah AF, Rafi M, Widodo H, Rohman A, Windarsih A. Review on in vitro antioxidant activities of Curcuma species commonly used as herbal components in Indonesia. Food Res 2020;2:286-93.  Back to cited text no. 17
    
18.
Agunloye OM, Oboh G, Ademiluyi AO et al. Cardio-protective and antioxidant properties of caffeic acid and chlorogenic acid: mechanistic role of angiotensin converting enzyme, cholinesterase and arginase activities in cyclosporine induced hypertensive rats. Biomed Pharmacother 2019;109:450-8.  Back to cited text no. 18
    
19.
Damasceno SS, Dantas BB, Ribeiro-Filho J, Araujo AM, da Costa GM. Chemical properties of caffeic and ferulic acids in biological system: implications in cancer therapy. A review. Curr Pharm Des 2017;23:3015-23.  Back to cited text no. 19
    
20.
Kinra M, Mudgal J, Mallik SB et al. Effect of coffee constituents, caffeine and caffeic acid on anxiety and lipopolysaccharide-induced sickness behavior in mice. J Funct Foods 2020;64:103638.  Back to cited text no. 20
    
21.
Zhang H, Zhao F, Peng A et al. l-Arginine inhibits apoptosis of ovine intestinal epithelial cells through the l-Arginine-Nitric Oxide pathway. J Nutr 2020;150:2051-60.  Back to cited text no. 21
    
22.
Lin Q, Huang H, Chen L, Shi G. Synthesis of caffeic acid coated silver nanoparticles for the treatment of osteoarthritis. Biomed Res 2017;28:1276-9.  Back to cited text no. 22
    
23.
Kumar S, Prahalathan P, Raja B. Syringic acid ameliorates L-NAME-induced hypertension by reducing oxidative stress. Naunyn Schmiedebergs Arch Pharmacol 2012;385:1175-84.  Back to cited text no. 23
    
24.
Pechanova O, Vrankova S, Cebova M. Chronic L-Name-treatment produces hypertension by different mechanisms in peripheral tissues and brain: role of central eNOS. Pathophysiology 2020;1:46-54.  Back to cited text no. 24
    
25.
Abdelwahab TS, Abdelhamed RE, Ali EN, Mansour NA, Abdalla MS. Evaluation of silver nanoparticles caffeic acid complex compound as new potential therapeutic agent against cancer incidence in mice. Asian Pac J Cancer Prev 2021;22:3189-201.  Back to cited text no. 25
    
26.
Sarhan OM, Hussein RM. Effects of intraperitoneally injected silver nanoparticles on histological structures and blood parameters in the albino rat. Int J Nanomedicine 2014;9:1505.  Back to cited text no. 26
    
27.
Sheikha MA, Soheir NA, SyragEldin FM. Synthesis, characterization and protection effect of black rice anthocyanins nano-composite against hepatotoxicity induced by methotrexate in rats. Rev Bras Biol 2022;84:e 248726.  Back to cited text no. 27
    
28.
Niehaus Jr WG, Samuelsson B. Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 1968;1:126-30.  Back to cited text no. 28
    
29.
Jiang ZY, Hunt JV, Wolff SP. Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Anal Biochem 1992;202:384-9.  Back to cited text no. 29
    
30.
Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys 1984;21:130-2.  Back to cited text no. 30
    
31.
Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972;47:389-94.  Back to cited text no. 31
    
32.
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra W. Selenium: biochemical role as a component of glutathione peroxidase. Science 1973;179:588-90.  Back to cited text no. 32
    
33.
Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82:70-7.  Back to cited text no. 33
    
34.
Roe JH, Kuether CA. The determination of ascorbic acid in whole blood and urine through the 2, 4–dinitrophenylhydrazine derivative of dehydroascorbic acid. J Biol Chem 1943;147:399-407.  Back to cited text no. 34
    
35.
Baker T, Lowndes HE, Johnson MK, Sandborg IC. The effects of phenylmethanesulfonyl fluoride on delayed organophosphorus neuropathy. Arch Toxikol 1980;46:305-11.  Back to cited text no. 35
    
36.
Saravanakumar M, Raja B. Protective effect of borneol in liver and kidney tissues in L-NAME-induced hypertensive rats; a FTIR report; oral presentation. Int J Nutr Pharmacol Neurol Dis 2011;1:19-26.  Back to cited text no. 36
    
37.
Silva H, Lopes NM. Cardiovascular effects of caffeic acid and its derivatives: a comprehensive review. Front Physiol 2020;11:595516.  Back to cited text no. 37
    
38.
Briones AM, Touyz RM. Oxidative stress and hypertension: current concepts. Curr Hypertens Rep 2010;2:135-42.  Back to cited text no. 38
    
39.
Harrison DG, Gongora MC, Guzik TJ, Widder J. Oxidative stress and hypertension. J Am Soc Hypertens 2007;1:30-44.  Back to cited text no. 39
    
40.
Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem 2006;6:1634-58.  Back to cited text no. 40
    
41.
Veerappan R, Senthilkumar R. Chrysin enhances antioxidants and oxidative stress in L-NAME-induced hypertensive rats. Int J Nutr Pharmacol Neurol Dis 2015;5:20.  Back to cited text no. 41
  [Full text]  
42.
Wu WM, Lu L, Long Y et al. Free radical scavenging and antioxidative activities of caffeic acid phenethyl ester (CAPE) and its related compounds in solution and membranes: a structure-activity insight. Food Chem 2007;105:107-15.  Back to cited text no. 42
    
43.
Yan-Chun Z, Rong-Liang Z. Phenolic compounds and an analog as superoxide anion scavengers and anti oxidants. Biochem Pharmacol 1991;42:1177-9.  Back to cited text no. 43
    
44.
Kono Y, Kobayashi K, Tagawa S et al. Antioxidant activity of polyphenolics in diets: rate constants of reactions of chlorogenic acid and caffeic acid with reactive species of oxygen and nitrogen. Biochim Biophys Acta 1997;1335:335-42.  Back to cited text no. 44
    
45.
Lee WJ, Zhu BT. Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols. Carcinogenesis 2006;27:269-77.  Back to cited text no. 45
    
46.
Nardini M, D’Aquino M, Tomassi G, Gentili V, Di Felice M, Scaccini C. Inhibition of human low-density lipoprotein oxidation by caffeic acid and other hydroxycinnamic acid derivatives. Free Radic Biol Med 1995;19:541-52.  Back to cited text no. 46
    
47.
Son S, Lewis BA. Free radical scavenging and antioxidative activity of caffeic acid amide and ester analogues: Structure−activity relationship. J Agric Food Chem 2002;50:468-72.  Back to cited text no. 47
    
48.
Wang X, Stavchansky S, Kerwin SM, Bowman PD. Structure-activity relationships in the cytoprotective effect of caffeic acid phenethyl ester (CAPE) and fluorinated derivatives: effects on heme oxygenase-1 induction and antioxidant activities. Eur J Pharmacol 2010;635:16-22.  Back to cited text no. 48
    
49.
Doiron JA, Leblanc LM, Hébert MJ et al. Structure-activity relationship of caffeic acid phenethyl ester analogs as new 5‐lipoxygenase inhibitors. Chem Biol Drug Design 2017;89:514-28.  Back to cited text no. 49
    
50.
Agunloye OM, Oboh G, Ademiluyi AO et al. Cardio-protective and antioxidant properties of caffeic acid and chlorogenic acid: mechanistic role of angiotensin converting enzyme, cholinesterase, and arginase activities in cyclosporine induced hypertensive rats. Biomed Pharmacother 2019;109:450-8.  Back to cited text no. 50
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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