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Review Article
 

Momordica charantia Linn. (Cucurbitaceae): Review on Phytochemistry and Pharmacology



Javed Ahamad, Saima Amin and Showkat R. Mir
 
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ABSTRACT

This review aims to present the information related to chemical composition of Momordica charantia Linn. (Cucurbitaceae), which is used in many Asian countries as a traditional functional food and medicine especially for the treatment of diabetes mellitus. Our main objective was to collect information about active constituents of this plant. Review of literature included PubMed searches with ‘Momordica charantia’, ‘Bitter gourd’ or ‘Bitter melon’ as initial key words. The search was further refined by looking for terms such as ‘Constituents’ (or composition) and ‘Activity’ (or effect) within the results. The earliest report of the chemical screening of M. charantia dates back to 1960. Since then several classes of compounds including cucurbitacins, sterols, alkaloids, proteins and triterpenoids have been isolated. Cucurbitacins are reported to be the main active constituents of M. charantia that have anti-hyperglycemic, anti-hyperlipidemic, hepatoprotective, anti-obesity, anti-cancer and anti-viral activities. The M. charantia is a rich source of chemically novel compounds and needs elaborate screening strategies to dwell into the pharmacological effects of its phyto-constituents at the molecular level.

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  How to cite this article:

Javed Ahamad, Saima Amin and Showkat R. Mir, 2017. Momordica charantia Linn. (Cucurbitaceae): Review on Phytochemistry and Pharmacology. Research Journal of Phytochemistry, 11: 53-65.

URL: https://scialert.net/abstract/?doi=rjphyto.2017.53.65
 
Received: October 11, 2016; Accepted: February 19, 2017; Published: March 15, 2017



INTRODUCTION

Momordica is a genus of about 60 species of annual or perennial herbaceous climbers belonging to family Cucurbitaceae. Momordica charantia Linn. is a monoecious climber found in tropical and subtropical regions, often under cultivation up to an altitude of 1500 m. It is mainly found in Africa, Asia and Australia. Two varieties of M. charantia are cultivated in India M. charantia var., charantia with large fruits that are fusiform in shape and M. charantia var., muricata that are identified by small, round fruits1. Momordica charantia fruits are commonly consumed as vegetable, which has formed a part of subcontinental diet since centuries. Its fruits, seeds and leaves are traditionally used to treat diabetes mellitus across India2. The fruits are used as tonic, stomachic, stimulant, emetic, anti-bilious and laxative. Fruit-pulp, leaf juice and seeds are anthelmintic. Fruit is useful in gout, rheumatism and sub-acute spleen and liver malfunction. It is supposed to purify blood and dissipate melancholia and gross humors3. Leaf juice is given in bilious affections as emetic and purgative. Fruit and leaves are both administered internally in leprosy, piles and jaundice. Leaf-juice is rubbed to soles in the burning of feet. Leaf juice along with a little turmeric powder is given for the nausea of children, as it acts as emetic and thus cleanses the stomach. Externally it is applied to the scalp in pustular eruptions, to burns and boils4.

There are a few comprehensive reviews about the efficacy and safety and clinical of M. charantia5,6. However, despite exhaustive phytochemical screening, no review on the phytochemistry of this plant is available. Our main objective was to collect information about active constituents of this plant. Review of literature included PubMed searches with ‘Momordica charantia’, ‘Bitter gourd’ or ‘Bitter melon’ as initial key words. The search was further refined by looking for terms such as ‘Constituents’ (or composition) and ‘Activity’ (or effect) within the results. This review summarizes previous and current information regarding its phytochemical and pharmacological screening.

PHYTOCHEMICAL REPORTS

Momordica charantia mainly contains cucurbitacins7-18, sterols15,19,20, triterpenoids16 and vicine21. The chemical structures of phyto-constituents isolated from M. charantia are summarized in Fig. 1.

Image for - Momordica charantia Linn. (Cucurbitaceae): Review on Phytochemistry and Pharmacology
Image for - Momordica charantia Linn. (Cucurbitaceae): Review on Phytochemistry and Pharmacology
Image for - Momordica charantia Linn. (Cucurbitaceae): Review on Phytochemistry and Pharmacology
Image for - Momordica charantia Linn. (Cucurbitaceae): Review on Phytochemistry and Pharmacology
Image for - Momordica charantia Linn. (Cucurbitaceae): Review on Phytochemistry and Pharmacology
Image for - Momordica charantia Linn. (Cucurbitaceae): Review on Phytochemistry and Pharmacology
Image for - Momordica charantia Linn. (Cucurbitaceae): Review on Phytochemistry and Pharmacology
Image for - Momordica charantia Linn. (Cucurbitaceae): Review on Phytochemistry and Pharmacology
Fig. 1:Chemical structures of phyto-constituents that are reported from Momordica charantia

Momordica charantia contains a diverse range of cucurbitacins like other vegetal curcurbits. Cucurbitacins represent a special class of compounds found exclusively among the members of Cucurbitaceae. The basic structure of a cucurbitacin (1) resembles a lanostane ring (2) except that the former bears a C-19 methyl group at C-9 rather than at C-10 as in the latter. Thus cucurbitacins are 19-(10α→9β)-abeo-10α-lanost-5-ene type systems. Most of the cucurbitacins found in M. charantia have an eight-membered branched side-chain at C-17. The side-chain is either saturated (3-5) or unsaturated (6, 7). A double bond is essentially present at C-5 that may shift to C-6 if C-5 is involved in epoxy ring formation. Additional double bonds may be present at C-23 (8-13) or C-24 (14-16). The C-19 methyl group found in cucurbitacins may get oxidized to an aldehyde, ketonic or carboxylic functionality. Cucurbitacins have one or more hydroxyl, keto, carboxyl, methoxy or acetoxy substitutions in their cyclic framework or in the side-chain. This has resulted in a greater diversity of both the structure and stereochemistry of cucurbitacins reported from M. charantia (17-20). Usually the cucurbitacins are tetracyclic, but some representatives have an extra epoxy ring due to formal cyclization between C-5 and C-19 as in goyaglycosides a-f and others (21-31). On the other hand, momordicosides represent a special group of cucurbitacins found only in M. charantia that have a C-19 methyl oxidized to an aldehyde group. Cucurbitacins in M. charantia are found either in glycosidic (25-32) or free form (33-53). In some cucurbitacins, a three-membered epoxy ring between C-5 and C-6 is formed (37-39). Polynorcucurbitacins have been also reported from M. charantia that may have a five-membered side-chain as in trinorcucurbitacins (34-36), three membered side-chain as in pentanorcucurbitacins (54-56) or no side-chain at all as in octanorcucurbitacin (57-60). Cucurbitacins with hydroxylation or methoxylation at C-7 and C-25 (61-70) are less common in M. charantia. Some of the constituents show exocyclic or endocyclic conjugated system (71-74). Still other members exhibit hydroxylation, alkylation, acetylation or glycosylation at one or more positions in cucurbitane framework (75-92). Besides cucurbitacins, M. charantia also contains triterpenoids (93-96), sterols (97-99), vicine (100) and p-methoxy benzoic acid (101).

PHARMACOLOGICAL REPORTS

Momordica charantia has a long history of human use in traditional medicine throughout the world. There is a plethora of reports of experimental and clinical evidences related to its different uses that are summarized below.

Antidiabetic and antihyperlipidemic activities: Charantin, an active fraction of M. charantia, when administered to normal rabbits has been reported to produce a gradual but significant fall in blood sugar level. However, in alloxan induced diabetic rabbits, the effects were more erratic. Pancreatectomy was found to reduce but not abolish the hypoglycemic effect of charantin indicating a dual mechanism of action20. Polypeptide-P, isolated from the fruits and seeds of M. charantia, showed a potent hypoglycemic effect when administered subcutaneously to gerbils and humans22.

Aqueous extract of immature fruits of M. charantia has been shown to partially stimulate insulin release from isolated β-cell of obese-hyperglycemic mice23. Oral feeding of ethanolic extract of M. charantia to normal rats prior to glucose loading increased hepatic and muscle glycogen content while significantly lowered blood sugar levels24. Oral administration of acetone extract of fruit powder of M. charantia for 15-30 days to alloxan-induced diabetic rats lowered the blood sugar and serum cholesterol levels to normal range25. Handa et al.21 found that vicine from the seeds of M. charantia on intraperitoneal administration caused a hypoglycemic response in normal fasting albino rats. The fruit juice significantly increased the number of β-cells in M. charantia treated animals when compared to untreated diabetic rats. The number of α-cells did not change significantly in M. charantia treated rats when compared with untreated diabetic rats26.

Yibchok-Anun et al.27 reported that protein extract from M. charantia significantly increased insulin secretion and increased glucose uptake in adipocytes. Acetone extract of whole fruit powder of M. charantia at dose levels of 25, 50 and 75 mg/100 g b.wt., lowered the blood glucose from 13.30-50% after 8-30 days treatment in alloxan-induced diabetic albino rats. Histological observations showed different phases of recovery of β-cells of the islets of Langerhans of pancreas28. Out of fourteen cucurbitane-type triterpene glycosides isolated from a methanol extract of M. charantia fruits, charantosides A-C were evaluated for α-glucosidase inhibitory effect, of which charantoside A showed moderate inhibitory activity against α-glucosidase17. Momordica charantia capsules in doses of 2000 mg day–1 demonstrated statistically significant improvement in fasting blood glucose as well as 2 hour postprandial blood glucose level29.

Choudhary et al.30 evaluated anti-hyperglycemic activity of fractionated M. charantia seed extracts in diabetic rats. Fasting blood glucose levels were evaluated before and after administration of different fractions (15 mg kg–1 b.wt.) of the seed extract. A soluble fraction of acid-ethanol extract of M. charantia after precipitation with ammonium carbonate designated as MC-3 showed the maximum anti-hyperglycemic activity and reduced blood glucose levels significantly. Perumal et al.31 evaluated the changes in urinary metabolite profile of the STZ-induced type 1 diabetic rats using M. charantia extract (100 and 200 mg kg–1 b.wt.). The results indicated that M. charantia was effective in lowering blood glucose level and also regulated the altered urinary metabolite profile.

Xu et al.32 isolated a water-soluble polysaccharide (MCP) from the fruits of M. charantia and the its effect was evaluated in alloxan-induced diabetic mice at 100, 200 and 300 mg kg–1 b.wt. for 28 days. Results showed that fasting blood glucose level was significantly decreased, whereas, the impaired glucose tolerance was markedly improved in alloxan-induced diabetic mice. Raish et al.33 investigated reno-protective nature of MCP by evaluating the anti-hyperglycemic, anti-hyperlipidemic and antioxidant proficiency in streptozotocin (STZ)-induced diabetic rats. The oral administration of MCP showed a significant normalization in the levels of markers of oxidative stress in the STZ-induced diabetic rats. The MCP treatment also illustrated a significant improvement in glutathione peroxidase, superoxide dismutase and catalase levels. Immunoblots of heme-oxygenase 1 and Nrf2 of MCP treated diabetic rats showed a significant up-regulation of both the proteins.

Anticarcinogenic activity: Kusamran et al.34 evaluated the effects of M. charantia on the levels of phase I enzymes, which include cytochrome P450, aniline hydroxylase and aminopyrine-N-demethylase and the phase II enzymes i.e., glutathione S-transferase in rat liver. It was demonstrated that bitter-gourd fruits contain compounds that act as phases I and II enzyme inducers and are capable of repressing some mono-oxygenases, especially those involved in the metabolic activation of chemical carcinogens. Ganguly et al.35 reported skin papilloma prevention by aqueous extract of M. charantia fruits. The results suggested a preventive role of water-soluble constituents of M. charantia fruit during carcinogenesis, which is mediated possibly by their modulatory effect on enzymes of the bio-transformation and detoxification system of the host. The oxygen free radical scavenging activity of the juice of M. charantia fruits is also reported36.

Wound healing activity: Sharma et al.37 reported significant wound healing activity in animals treated with M. charantia extract compared to those who received the standard and control treatments. In excision wound model, M. charantia extract treated animals showed a significant reduction in wound area and period of epithelization. The extract treated animals showed faster epithelization of wound than the control. The wound healing activity of olive oil macerate of M. charantia was evaluated in linear incision and circular excision wound models created in the buccal mucosa of the rat. Olive oil macerate of M. charantia showed significant wound healing activity both in incision (45.1%) and excision (89.8%) wound models and demonstrated anti-inflammatory activity with the inhibition value of 31.3% at the dose38 of 100 mg kg–1.

Anti-inflammatory and analgesic effects: Momordica charantia fruit extract exhibits a dose dependent anti-inflammatory activity in carrageenan-induced paw edema in rats. The oral administration of M. charantia ethanolic extract showed 42.10% anti-inflammatory effect at dose 500 mg kg–1 b.wt. The fruit extract was also tested for analgesic activity in acetic acid induced writhing test and tail immersion test in mice. The oral administration of M. charantia extract significantly inhibited acetic acid induced writhing and tail immersion induced pain at dose 500 mg kg–1 b.wt.39. The anti-inflammatory and antiulcer potential of seeds of M. charantia have been attributed to the presence of antioxidant in it40. Methanolic extract of the seeds from unripe fruits of M. charantia has been shown to produce a marked dose-dependent analgesic effect in mice and a much weaker effect in rats by using different test systems for the two species41. Naloxone pretreatment failed to modify the analgesic response, suggesting that opioid receptors were not involved42.

Hepatoprotective action: Bitter gourd juice and seed extract (10 mL kg–1 b.wt., daily for 30 days) exhibited hepatoprotective effects by elevating serum γ-glutamyl transferase and alkaline phosphatase enzymes43.

Antiviral potential: Momordica charantia fruit extract is reported to inhibit the growth of Herpes simplex virus I44 and human immunodeficiency virus I45. Increased T-cell count and a normalization of the CD4/CD8 ratio seemed to occur in three HIV positive patients given regular doses of M. charantia fruit juice46.

Antipyretic effects: The ethanolic extracts of M. charantia fruit (500 mg kg b.wt.) showed antipyretic effect in a study that was carried out using yeast-induced pyrexia in rats. The antipyretic activity of M. charantia was postulated to be due to individual or combined action of bioactive constituents present in it47.

Antimalarial and larvicidal activity: Momordica charantia was evaluated for antimalarial activities against different Plasmodium species. The study showed moderate in vivo activity of M. charantia extract against rodent malaria Plasmodium vinckei petteri and an excellent anitimalarial activity in vitro on Plasmodium falciparum48. Momordica charantia has shown good larvicidal activity against three breeding mosquito species: Anopheles stephensi, Culex quinquefasciatus and Aedes aegypti 49.

CONCLUSION

Momordica charantia is a rich source of chemically novel compounds and needs exhaustiue screening against new targets in future. This compilation of its phytochemical and pharmacological reports will help the researchers in dereplication and designing new investigational strategies. The biologically active cucurbitacins, momordicosides and steroidal glycosides from M. charantia are the main focus of this review.

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