International Journal of Nutrition, Pharmacology, Neurological Diseases

REVIEW ARTICLE
Year
: 2022  |  Volume : 12  |  Issue : 3  |  Page : 93--98

Insight on Synsepalum dulcificum: A Bioactive Compound on Taste Modification and Its Biological Properties


Vidya G Doddawad1, S Shivananda2, CS Vidya3, B Madhu4, BM Gurupadayya5,  
1 Department of Oral Pathology and Microbiology, JSS Dental College and Hospital, A Constituent College of JSS Academy of Higher Education and Research, Mysore, Karnataka, India
2 Department of Oral and Maxillofacial Surgery, JSS Dental College and Hospital, A Constituent College of JSS Academy of Higher Education and Research, Mysore, Karnataka, India
3 Department of Anatomy, JSS Medical College, A Constituent College of JSS Academy of Higher Education and Research, Mysore, Karnataka, India
4 Department of Community Medicine, JSS Medical College and Hospital, A Constituent College of JSS Academy of Higher Education and Research, Mysore, Karnataka, India
5 Department of Pharmaceutical Chemistry, JSS College of Pharmacy, A Constituent College of JSS Academy of Higher Education and Research, Mysore, Karnataka, India

Correspondence Address:
S Shivananda
Associate professor, Department of oral and maxillofacial surgery JSS Dental College and Hospital (A Constituent College of JSS Academy of Higher Education & Research), Mysore 570015
India

Abstract

The miracle fruit plant or miracle berry plant (Synsepalum dulcificum or Richadelladulcifica) is a unique medicinal plant with characteristics of taste-modifying function due to the presence of the glycoprotein miraculin. It also has high antioxidant effect. Alkaloids, vitamins, vegetable oil, phenolic acids, flavonoids, and amino acids are among the biologically active components found in the fruit. This fruit is not much known in all places of the world, so it will be used to treat a variety of medical conditions. Pharmacological medicine has proven that not only the fruit but also the other parts of the plant are helpful, based on their phytochemical properties. This fruit can be used in the baking food items, drinks, cosmetics, medicines, and coloring agents. In this article, we (authors) intend to describe on cultivation, phytochemistry, mechanism of action, extraction, purification, and preservation of fruit, as well as its nutritional and pharmacological benefits, applications in numerous fields, limitations, and future prospects. It is hard to believe that this berry is still unexplored for its use in medical area.



How to cite this article:
Doddawad VG, Shivananda S, Vidya C S, Madhu B, Gurupadayya B M. Insight on Synsepalum dulcificum: A Bioactive Compound on Taste Modification and Its Biological Properties.Int J Nutr Pharmacol Neurol Dis 2022;12:93-98


How to cite this URL:
Doddawad VG, Shivananda S, Vidya C S, Madhu B, Gurupadayya B M. Insight on Synsepalum dulcificum: A Bioactive Compound on Taste Modification and Its Biological Properties. Int J Nutr Pharmacol Neurol Dis [serial online] 2022 [cited 2022 Dec 8 ];12:93-98
Available from: https://www.ijnpnd.com/text.asp?2022/12/3/93/357214


Full Text



 Introduction



Thaumatin, monellin, mabinlin, pentadin, brazzein, neoculin (curculin), and miraculin are taste modifiers and sweeteners and are classified into three groups as follows:protein (thaumatin, monellin, mabinlin, pentadin, and brazzein),protein inducers (miraculin), andcombination of both (neoculin).

Synsepalum dulcificum or Richadelladulcifica is commonly known as miracle plant, miracle fruit, or magic fruit.[1] Miracle berry plant is a shrub which was first found in West and Central Africa.[2] The name “miracle fruit” originated from the major component “miraculin,” which is responsible for taste alteration. Miracle fruit was first discovered in the 17th century by European explorers, and was later described by Daniell in 1852.[3] Kurihara and Beidler identified the miraculin chemical compound in 1968,[3] and Brouwer et al. termed it.[4] The Indian variety of miracle berry is known as Gymnema sylvestre with botanical synonyms Asclepias geminata, Periploca sylvestris, and Marsdenia sylvestris. It is also known as Gudmar or sugar destroyer.[5]

The miraculin fruit has a unique taste-modifying feature that results in an increase in sweetness and a decrease in sourness.[6] Miracle fruit can be consumed raw or processed, and there is a growing interest in the plant’s and its products’ potential applications in the cosmetics industries, pharmaceutical industries (particularly in diabetes, cancer, and obesity), and the food industry (including beverages, artificial sweeteners, and food color). This paper attempts to provide an extensive scientific assessment of the therapeutic properties, phytochemical content, and nutritional benefits of this plant.

Cultivation of S. dulcificum

Miracle plant is a Sapotaceae family plant that grows up to a height of around 3 m in cultivation. Their leaves measure 5 to 10 cm in length and 2 to 3.7 cm in width and are grown in shady areas with plenty of water and nutrients.[2] Changes in the color of the fruit in S. dulcificum can be seen starting at the yellowish stage and become more noticeable as the fruit ripens (red color). Seed maturation was also indicated by reddish brown to black coloration. At 70 to 74 days following the flower blossom, the color of S. dulcificum fruit changes to entirely bright red.[7] The optimum temperature needed for miracle fruit plant survival is >7°C.

Flowers are cream in hue while budding, but mature to a dark red or brown tint. The ripe fruit is an indigenous fruit with small ellipsoid berries that are brilliant red in color. The fruits are typically packed at the branches’ terminals. The fruit is around 2 to 2.5 cm long, 1 cm wide, and has a coffee bean form. It has a huge elliptical seed that is dark brown in color encased in a translucent pulp with a thin red skin. The pulp contains the sweetening action. The flowers blossom in the summer, and the fruits can be harvested in the winter.[5] Only the miraculin fruit accumulates miraculin, and production begins 6 weeks after pollination [Figure 1].{Figure 1}

Composition of S. dulcificum

Previous studies have been reported on the nutritional properties of the miracle fruit plant, in addition to its medicinal effects. Carbohydrate, fibers, volatile oils, tannins, alkaloids, cardiac glycosides, polyphenols, flavonoids, resins, and minerals are abundant in miracle berry, leaves, and roots.[5],[8] Miracle fruit is a good source of flavor and color and also has antioxidant property in addition to it.

The fruits are rich in vitamins, proteins, lipids, and dietary phytochemicals which are necessary for good health and immunity. Vitamins A, C, D, E, and K are present in the berries. They are also rich in both essential (lysine, leucine, isoleucine, phenylalanine, threonine, histidine, methionine, valine, tryptophan, and so on) and nonessential (glycine, proline, serine, tyrosine, and glutamic acid) amino acids. The deep red color of the fruit is due to presence of anthocyanins, which is an anticancer agent.[9] The fruits also contain other antioxidative phytochemicals like: epicatechin, rutin, quercetin, myricetin, kaempferol, gallic, ferulic, and syringic acid, delphinidin glucoside, cyanidin galactoside, and malvidin galactoside, α-tocotrienol, terpenoids, phenolic compounds, and lutein.[3] The fruit contains phytosterols, but some studies show that the fruit contains no fatty acids however the seed contains 10 different unsaturated fatty acids, including neutral lipids and cerebrosides.[10],[11] The fruit pulp contains negligible amount of minerals such as: calcium iron, zinc, copper, chromium, and cobalt with no lead detected.[12] Leaves contain cyanidin-3-monoglucoside, cyanidin-3-monogalactoside, delphinidin-3-monoarabinoside, cyanidin-3-monoarabinoside, and delphinidin-3-monogalactoside. The main compound of the fruit, miraculin (having taste modifying property), is a glycoprotein consisting of sugars (glucosamine, mannose, fucose, xylose, and galactose), nitrogen, carbohydrates, and nearly 191 amino acid residues [Figure 2].[5]{Figure 2}

Structure of miraculin − taste modifying agent

According to a number of studies,[1],[4],[6] the taste-altering function of S. dulcificum fruit is because of “miraculin,” a 44-kDa active glycoprotein component. Kurihara and Beidler isolated and refined miraculin for the first time in 1968, while Theerasilp et al. examined the chemical structure and sequence of miraculin in 1989. This fruit can be utilized to provide color, flavor, and sweetness.[12] The pulp of the fruit is the part which contains miraculin and accounts for only 4.44% of the fresh fruit’s weight.[10]

Miraculin is resistant to pH changes and transforms sour foods into sweet foods with a taste comparable to sucrose. Miraculin does not have a sweet flavor, but when activated at an acidic pH, it changes the taste from sour to sweet. It is 400,000 times sweeter than sucrose in molar terms.[13] Miraculin is a macromolecule that is a homodimer of two glycosylated polypeptide glycoproteins with 191 amino acids and a molecular weight that ranges from 24,000 to 45,000 Da in monomeric form.[4],[7]

Mechanism of taste-modifying action of miraculin

The proposed mechanism of interaction between miraculin, a taste-modifying protein, and taste receptors T1R2 and T1R3 differs from the fundamental sweet chemical pathway. Taste buds in taste papillae on the tongue, upper and lower palates, and throat are the first to detect flavor. About 150 cells contain each taste bud. These cells’ cell membranes generate microvilli, which houses the nerve receptor. Chemicals dissolved in saliva, oil, and water are picked up by these nerve receptors. An action potential is generated and cranial nerves carry the taste impulses, and relay them to nucleus tractus solitarius. The gustatory signal is subsequently directed to the pons’ parabrachial nucleus. Then it is relayed to thalamus, amygdala, and insula of brain, and this complicated system is combined into a gustatory pathway relating to distinct taste attributes [Figure 3].{Figure 3}

Sour and salt perceptions have relative mechanisms, while sweet, bitter, and umami perceptions have similar pathways. Despite the fact that certain taste mechanisms have similar patterns, sensory receptors on taste buds are unique to one of the five taste senses.[14]

Miraculin binds to the epithelial plasma membrane of the taste receptor, which is a heterodimer made up of T1R2 and T1R3, both of which appear to have sweet ligand binding sites. T1R2 sites bind small compounds, while T1R3 sites bind large molecules. These receptors undergo a conformational change in the presence of acidic environment, and glycans associated with miraculin bind and activate them. Depending on the pH of food or drink consumed, miraculin may function as a selective agonist (at acidic pH) or antagonist (at neutral pH) of taste receptor type 1 member 2 (TAS1R2)/taste receptor type 1 member 3 (TAS1R3) sweet taste receptors.[3] In the presence of protons (H+), the receptor undergoes a structural shift, causing the carbohydrate part of the miraculin molecule to attach to the sweet receptor site, resulting in a pH-dependent activation of human sweet taste receptor cells (between pH 4.8 and 6.5). The most intriguing element of this mechanism is that, unlike sugary foods, miracle fruit does not provide a sweet taste when consumed alone, but does so when combined with H+ ions. At the subcortical level, the sour taste disappears, while the sweet taste neuronal signal reaches the cortex of brain. When one of these ligands binds to a sweet taste receptor, the G-protein coupled receptor is directly activated, resulting in the sense of sweetness. The psychophysiology character of taste experience is demonstrated by the method of sensory transduction of a typical sweet taste receptor function.[4]

G-coupled protein C receptors are heterodimers of TAS1R2/TAS1R3 with three primary domains namely transmembrane domain, N-terminal segment Venus flytrap domain (VFD), and cysteine-rich domain. At an acidic pH, miraculin’s hypothesized mechanism of action begins with its interaction with the VFD of TAS1R2/TAS1R3 as an active form. There are two free forms of these receptors namely form I (open-open-R), which has two open sites for ligand binding, and free form II, which has only one open site for ligand binding.[12] The action starts a few seconds after the fruit is consumed and lasts between 30 minutes to 2 hours, after which salivary amylase dissociates miraculin from taste receptors.[3]

Extraction and purification of miraculin

There are several investigators who illustrated the method of extraction of miraculin from miracle fruit. But, the miraculin has been purified by using various methods like solvent extraction method from polar to nonpolar and from nonpolar to polar in succession, ion-exchange chromatography technique, immobilized metal affinity chromatography, and reverse micelle system.[5]

As reported by Inglett and Chen,[11] after freeze drying pulp and seeds were separated. Individually, the skin, pulp, and seeds were pulverized to a fine powder. They described how to extract fruit pulp in two processes utilizing Adom and Liu’s modified extraction method. Sequential extraction was the first approach, which consisted of two steps: double extraction for free chemicals and alkaline extraction for bound compounds. The direct extraction method was the second method.

The process of extracting the fruits and leaves of this plant was carried out by Dioso et al. The miracle plant’s leaves and fruits were soaked in ethanol and then evaporate at room temperature.[10]

He et al. used the Theerasilp and Kurihara methods to modify the extraction procedure for miraculin from miracle berry. The lyophilized pulp powder was suspended in water and homogenized in this technique. The silt was homogenized in a 0.5 M sodium chloride solution after the homogenate was centrifuged. The colorless supernatant was then centrifuged again and freeze-dried.[10]

Restriction, maintenance, and preservation of miracle berry fruit/seed

The miracle berry, also known as Richadelladulcifica, is extremely perishable. It is thermolabile and inactivated at pH < 3 and pH > 12. As it gets destroyed at high temperatures, it is not utilized in cooking or processed foods. As a result, it can be preserved utilizing a polysaccharide, chitosan coating process. The miracle fruit can also be freeze-dried for 6 months at −20°F before usage without substantial degradation. The miraculin protein is extremely stable, and it can be stored in pure form or in solution for up to 6 months without losing function, and long-term storage can be done in Ziploc freezer bags.[5]

The seeds of S. dulcificum do not survive at <10% moisture content, but they can be stored for a short period of time (maximum 7 days) at low temperatures (e.g., 10°C or 4°C). Seeds stored at a temperature equivalent to ambient conditions (25°C) had the highest viability and germination.[7]

Nutritional and health uses of S. dulcificum

In Malaysia, South Africa, and other countries, all portions of S. dulcificum plant are used to treat or manage a variety of human diseases and disorders as traditional herbal medicine. The leaves (90%) are the most important part of plants in traditional medicine, followed by the root (7%), bark (1.5%), stem (1%), and fruit (0.5%). As reported in earlier literature, there are at least two major types of ailments for which this plant is used for treatment namely, diabetes and sexually-related diseases.[10]Diabetes, malaria, hyperthermia, and enuresis are all treated using the leaves.The bark of the tree is used to cure prostate problems.For optimum dental and oral health, the branches are used as a vegetable toothbrush.For the treatment of gonorrhea, the root is macerated in local gin or soda water.The leaves of S. dulcificum are used to treat asthma, male infertility, diabetes, weight loss, and cancer.Fruit has traditionally been used to sweeten sour dishes and beverages like koko and kenkey, which are prepared from fermented maize, millet, and palm wine.Erectile dysfunction is treated with the bark.Crushed S. dulcificum leaves are used for postnatal care, and also as appetizer and sweetener.Diabetic and obese patients are known to consume this fruit.

Pharmacological activities of S. dulcificum

Long-term consumption of fruit may lead to obesity and other chronic diseases like cardiovascular disease and cancer.[5] Antidiabetic, anticancer, antihyperuricemic, anticonvulsant, antioxidant, hypolipidemic, and antialopecia activities are some of the pharmacological actions of S. dulcificum that have been reported [Figure 4].{Figure 4}

Antidiabetic activity

The effect of miracle fruit (S. dulcificum) on insulin sensitivity was considerable after treatment with miracle fruit powder. S. dulcificum fruit (50% and 100%) and leaf (50% and 100%) extracts had significant hypoglycemic effects on blood glucose levels. Miraculin and other phytochemicals found in the plant, such as flavonoids and saponins, may be responsible for the observed hypoglycemic outcome. α-amylase and α-glucosidase inhibitory actions were also observed in S. dulcificum fruit and leaf extracts.

Anticancer activity

In vitro, miracle fruit, which is best known for its antioxidant properties, has been shown to inhibit malignant cell proliferation.[3] Previous research report states that two of the chemicals present in S. dulcificum, (þ-syringaresinol and þ-epi-syringaresinol) exhibit inhibitory effects on human skin cancer cells, and considerable antioxidant activity in vitro.

The effect of aqueous leaf extracts of miracle fruit on 2-aminoanthracene and 4-nitroquinoline-N-oxide-induced mutation and oxidative damage was studied and reported that the mutagenicity was inhibited.

The effect of S. dulcificum berry and stem extracts on the expression of early apoptotic genes, c-fos and c-jun, on colorectal cancer cells (human colorectal carcinoma-116 (HCT-116), Human colon cancer cell (HT-29)), as well as their cytotoxic action on colorectal cancer cells (HCT-116, HT-29) has also been reported. The c-fos and c-jun genes code for activator protein 1 are transcription factors involved in cell processes such as cell proliferation, differentiation, and death. Both extracts dramatically increased c-fos and c-jun expression, aiding cytotoxicity in colorectal cancer cells.

Antihyperuricemic activity

The enzyme xanthine oxidase is involved in the synthesis of uric acid in animals. The xanthine oxidase activity will be inhibited by the antihyperuricemia action of S. dulcificum fruit extract which will prevent systemic diseases, like gout.

Anticonvulsant activity

The anticonvulsant potential of S. dulcificum seed aqueous fraction was tested in mice and proved that specific phytochemicals in S. dulcificum seed extract have anticonvulsant activity, and inhibitory neurotransmission was due to a mild affinity for the gamma aminobutyric acid (GABA) receptor’s picrotoxin (PTX) binding site.

Antioxidant activity

Antioxidants protect against the harmful effects of oxidative stress. In miracle berry pulps, antioxidant phytochemicals such as flavonoids, phenols, terpenoids, and amides exist,[12] all of which are capable of boosting health. The antioxidant and radical scavenging activities of methanol extracts of S. dulcificum fruits, leaves, roots, and seed were tested in vitro, and it was concluded that S. dulcificum is rich in antioxidant content. A few studies have also found a decrease in hepatic malondialdehyde levels and an increase in glutathione S-transferase enzymes.

Hypolipidemic activity

Cholesterol-lowering activity of S. dulcificum was found in a 2% ethanolic extract of S. dulcificum seed, leaves, and dry pulp, which decreased total cholesterol in plasma, mainly due to active triterpenoids in the extract.

Antialopecia activity

The efficacy of S. dulcificum seed oil and its influence on hair loss was also studied in healthy women, with the conclusion that manufactured product of S. dulcificum seed could be a safe and effective option for strengthening and repairing damaged hair.[11]

Clinical application in taste disorder

Dysgeusia can cause lack of appetite and even malnutrition, which can have a negative impact on patient’s quality of life and reduce the immune system’s functionality, as well as the efficacy of clinical therapies as shown in [Figure 5]. Chemotherapy can modify taste perception, which is why changes in taste perception are so crucial in conditions like cancer (dysgeusia). Furthermore, because chemotherapy weakens the immune system, increasing the risk of infection, it is critical to avoid malnutrition in order to maintain a healthy immune system.[3]As a result, “miracle fruit” will be given to chemotherapy patients to boost meal palatability., Miracle fruit was created as a sweetness enhancer. It contains miraculin, a protein that binds to sweet receptors on the tongue and converts sour meals to sweet. For a short while, disagreeable tastes such as metallic can be hidden. Health care practitioners can use the management options on cancer patient forums as a guideline to help patients who are experiencing a metallic taste. Furthermore, for these cancer patients, using miracle fruit and rinsing with chelating agents such as lactoferrin and ethylenediaminetetraacetic acid (EDTA) has more worth.[15]{Figure 5}

Commercial availability

Phytochemicals from S. dulcificum have been employed in a variety of industrial and commercial applications including medicine, cosmetics, flavoring agents, according to several reports. S. dulcificum is commercially important and has the potential to help impoverished countries generate income, empower smallholder farmers, and grow economically.[2] Miraculin is available commercially in various forms like tablets, granules, powder, juice extract, and sour beverages.[3],[4],[13] “mberry, mberry, US” the most often used commercially available freeze-dried miracle fruit tablet, is dissolved in the oral cavity and kept for 5 minutes without chewing.[6]

 Conclusion and Future Perspectives



In the aspect of medicine, S. dulcificum possesses nutritional and pharmacological health benefits. Various parts of the S. dulcificum plant are used extensively in the medicinal and dental fields. These plants can be used in the culinary, cosmetics, and pharmaceutical sectors in many forms. There is a lack in the miraculin metabolite can be used as biomarker in various disease and its pharmacological effect is not completely understood. Researchers have conducted numerous studies on this herb, but there is a lack of an appropriate standardized dosage and safety evaluation for usage in therapeutic purposes. As a result, ongoing research should be required in order to produce a medicine for the treatment of a variety of disorders and miraculin metabolite can be used as biomarker for identification of various disorders.

The miracle fruit contains a variety of bioactive compounds with pharmacological activity, although their ethnomedical applications are still in the works. People are more aware of health and fitness these days, so natural sweeteners that mirror sugar and are economical with low-calorie measures are desirable. This information encourages a higher number of people to accept fruits, boosting their use and acceptance in human diets.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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