THE EFFICACY OF CUCURBITANE TYPE TRITERPENOIDS, GLYCOSIDES AND PHENOLIC COMPOUNDS ISOLATED FROM MOMORDICA CHARANTIA: A REVIEWHTML Full Text
THE EFFICACY OF CUCURBITANE TYPE TRITERPENOIDS, GLYCOSIDES AND PHENOLIC COMPOUNDS ISOLATED FROM MOMORDICA CHARANTIA: A REVIEW
Ekramul Haque*1, M. Badrul Alam 2 and M. Sarowar Hossain 2
Department of Pharmacy, BRAC University 1, Dhaka, Bangladesh
Department of Pharmacy, Atish Dipankar University of Science & Technology 2, Dhaka, Bangladesh
Momordica charantia Linn. which has been used mainly for edible purposes at different countries of the world including South East Asia and has also been extensively used in traditional medicines for the cure of various ailments. M. charantia belongs to the cucurbitaceae family. Extensive research has been carried out on the fruit, leaves, and seeds of the plant. Most importantly, all these research works have shown its efficacy on various cancer cell lines like lymphoid leukemia, lymphoma, choriocarcinoma, melanoma, breast cancer, skin tumor, prostatic cancer, squamous carcinoma of tongue and larynx, human bladder carcinomas and on Hodgkin’s disease. Clinical reports of some research on the use of M. charantia in diabetes and cancer patients showed promising results. The main active constituents of M. charantia are cucurbitane type triterpenoids which have some potent biological and pharmacological activities including antidiabetic, anti-obesity, anticancer, anti-HIV, anti-feedant and anti-oviposition activities. Since in the early 1960’s the constituents of M. charantia have been investigated and several classes of secondary metabolites including cucurbitane-type triterpenoids, glycosides and phenolic compounds have been isolated and their structures were determined. This review summarizes the previous and current information regarding phytochemical constituents of M. charantia and their pharmacological effects that provide the scope for future research in this aspect.
|Keywords:Momordica charantia, Phytochemistry,
INTRODUCTION: Plants and herb preparation have been traditionally use for the cure of various ailments from ancient times and even today all over the world, 80% of the population continues to use traditional medicine for primary health care. In the past decade, therefore, research has been conduct on scientific evaluation of traditional drugs of plant origin. Momordica charantia is one such plant that has been frequently used as medicine from time immemorial 1, 2.
Momordica charantia, a climber belonging to family Cucurbitaceae, is commonly known as bitter gourd or bitter melon in English and karela in Bengali. Momordica means, to bite (referring to the jagged edges of the leaf, which appear as if they have been bitten). All parts of the plant, including the fruit have bitter taste. The fruit is oblong and resembles a small cucumber; young fruit is emerald green that turns to orange-yellow when ripe. It is an herb, grows in tropical areas of Asia, Amazon, East Africa, and the Caribbean and cultivated throughout the world for its use as vegetable as well as folk medicine.
The plant has been used traditionally as medicine in developing countries like Brazil, Bangladesh, China, Colombia, Cuba, Ghana, Haiti, India Mexico, Malaya, New Zealand, Nicaragua, Panama and Peru. Some of its common uses in the above countries are for diabetes, as a carminative and in the treatment of colics 3-5. Topically it is used for treatment of wounds, internally as well as externally for management of worms and parasites. It is also used as emmenagogue, antiviral for measles and hepatitis. In Turkish folk medicine, mature fruits of M. charantia are used externally for rapid healing of wounds and internally for treatment of peptic ulcers 5.
In Bangladesh, various medicinal properties are claimed for M. charantia that include antidiabetic, abortifacient, anthelmintic, contraceptive, antimalarial and laxative and is used for treatment of dysmenorrhea, eczema, emmenagogue, galactagogue, gout, jaundice, kidney (stone), leprosy, leucorrhea, piles, pneumonia, psoriasis, rheumatism and scabies. However, it is commonly consumed as vegetable 6.
During the last few decades tremendous research work has been carried out with M. charantia extract to see the antidiabetic, antiviral, antitumor, antileukemic, antibacterial, antihelmentic, antimutagenic, antimycobacterial, antioxidant, antiulcer, anti-inflammatory activities along with hypo- cholesterolemic, hypo-triglyceridemic, hypo- tensive, immunostimulant, and insecticidal properties 6-8. This review aims to highlight the main phytochemical constituents of M. charantia with their biological properties which support for future research on this plant.
Phytochemistry: The reported data showed that cucurbitane type triterpenoids are the main and common phytochemicals present in the Momordica charantia. More than 50 cucurbitacins so far have been isolated from this plant together with glycosides, saponins, alkaloids, fixed oils, proteins, steroids, flavonoids and phenolic compounds. Research has found that the leaves are nutritious sources of calcium, magnesium, potassium, phosphorus and iron; both the edible fruit and the leaves are great sources of the vitamins A, C and B 3, 8-9.
Cucurbitane type triterpenoids: The terpenoids, referred to as isoprenoids, are a class of natural products and related compounds formally derived from five carbon isoprene units. The cucurbitacins are a typical group of cucurbitane type triterpenoids found in plants and belonging to the cucumber family (Cucurbitaceae) and the main chemical constituents of M. charantia. The following cucurbitane type triterpinoid are isolated from different part of M. charantia (Fig. 1)
Charantin, a mixture of two compounds, namely, sitosteryl glucoside and stigmasteryl glucoside 10; kuguacins A-S 11-12; 3β, 25-dihydroxy-7β-methoxy cucurbita-5, 23(E)-diene, 3β-hydroxy-7β, 25-dimethoxy cucurbita-5, 23(E)-diene, 3β, 7β, 25-trihydroxy cucurbita-5, 23(E)-diene-19-al, 5β, 19-epoxycucurbita-6, 23(E)-diene-3β, 19, 25-triol, 5β, 19-epoxy-19-methoxycucurbita-6,23(E)-diene-3β, 25-diol 13; 3β, 25-dihydroxy-5β,19-epoxycucurbita-6, 23(E)-diene 12; momordicine I, II and III 14; karavilagenin A, B, C, D and E 15-16; 19(R)-methoxy-5β,19-epoxycucurbita-6, 23-diene-3β, 25-diol, 5β, 19-epoxycucurbita-6, 23(E)-diene-3β, 25-diol 15; 3β, 7β-dihydroxy-25-methoxy cucurbita-5, 23(E)-diene-19-al 17; 23(E)-25-methoxy cucurbita-23-ene-3β, 7β-diol, 23(E)-cucurbita-5, 23, 25-triene-3β, 7β-diol, 23(E)-25-dihydroxy cucurbita-5, 23-diene-3, 7-dione, 23(E)-cucurbita-5, 23, 25-triene-3, 7-dione, 23(E)-5β, 19-epoxycucurbita-6, 23-diene-3β, 25-diol, 23(E)-5β, 19-epoxy-25-methoxy cucurbita-6, 23-diene-3β-ol 18; cucurbita-5, 23(E)-diene-3β, 7β, 25-triol, 3β-acetoxy-7β-methoxy cucurbita-5, 23(E)-diene-25-ol, cucurbita-5(10), 6, 23(E)-triene-3β, 25-diol, cucurbita-5, 24-diene-3, 7, 23-trione 19; (19R, 23E)-5β, 19-epoxy-19-methoxy cucurbita-6, 23,25-triene-3β-ol, (23E)-3β-hydroxy-7β-methoxycucurbita-5, 23, 25-triene-19-ol, (23E)-3β-hydroxy-,7β, 25-dimethoxycucurbita-5, 23-diene-19-ol, (19R, 23E)-5β, 19-epoxy-19, 25-dimethoxycucurbita-6, 23-diene-3β-ol, (19R, 23E)-5β, 19-epoxy-19-methoxy cucurbita-6, 23-diene-3β, 25-diol 20.
FIG. 1: MAJOR CUCURBITANE TYPE TRITERPINOID ISOLATED FROM M. CHARANTIA (CONTINUED)
FIG. 2: MAJOR CUCURBITANE TYPE TRITERPINOID ISOLATED FROM M. CHARANTIA
Cucurbitane type triterpene glycoside: Cucurbitane glycoside, form with the substitutions at C-2 and/or C-3 position of the main skeleton of cucurbitanes, are abundant in the plants of genus Momordica. Momordicosides A-E 21-22, all lacking an oxygen function at C-11, the first cucurbitane glycoside have been isolated from the seeds of M. charantia. Following cucurbitane glycosides were also isolated (Fig. 2). Charantosides I-VIII 23; momordicosides F1, F2, G, I, K, L, M, N, O, Q, R, S and T 24-26; Karaviloside I, II, III, IV, V, VI, VII, VIII, IX, X and XI 15, 16; 3-O-β-D-allopyranosyl, 7β, 25-dihydroxycucurbita-5, 23(E)-diene-19-al 13; 3-O-β-D-allopyranosyl, 7β, 25-dihydroxy cucurbita-5(6), 23(E)-diene-19-al, 3-O-β-D-allo pyranosyl, 25-methoxy cucurbita-5(6), 23(E)- diene- 19- ol 24; Goyaglycoside- a, -b, -c, -d, -e, -f, -g and –h 27. A new steroidal glycoside, 24(R)-stigmastan-3β, 5α, 6β-triol-25-ene 3-O-β-gluco pyranoside was also isolated from M. charantia 28.
FIG. 3: MAJOR CUCURBITANE TYPE TRITERPINOID GLYCOSIDE ISOLATED FROM M. CHARANTIA (CONTINUED)
FIG. 4: MAJOR CUCURBITANE TYPE TRITERPINOID GLYCOSIDE ISOLATED FROM M. CHARANTIA (CONTINUED)
Oleanane type triterpene saponins: Murakami et al., 28 have reported the goyasaponins I, II and III present in the fresh fruit of Japanese M. charantia.
Phenolic and flavonoid compound: HPLC analysis has been proved that leaf, stem, fruit (green and ripe) contains phenolic compounds like galic acid, tannic acid, (+)-catechin, caffeic acid, p-coumaric, gentisic acid, chlorogenic acid and epicatechin 29-30 (Fig. 3).
FIG. 5: PHENOLIC COMPOUND DETERMINED BY HPLC FROM M. CHARANTIA
Miscellaneous: The essential oil obtained from the seeds of M. charantia was analyzed by GC/MS. Twenty-five components, representing 90.9% of the oil, were identified and among them trans-nerolidol, apiole, cis-dihydrocarveol and germacrene D were the main constituents 31. Trypsin inhibitors e.g. MCTI-II’ and BGIT 32, elastase inhibitors 33, guanylate cyclase inhibitors 34 and α-glucosidase inhibitor e.g. D-(+)-Trehalose 35 are reported. Moreover, HIV inhibitory proteins like MRK29 (MW: 28.6 KDa) and MAP30 (MW: 30,000 KDa) and lectin were also documented 36. α-eleostearic acid and its dihydroxy derivative, strongly inhibited the growth of cancer and fibroblast cell lines like HL60 leukemia and HT29 colon carcinoma, were also isolated from M. charantia 37.
Antidiabetic activity: All parts (fruit pulp, leaves, seeds and whole plant) of M. charantia showed hypoglycemic activity in normal animals 38-40 and antihyperglycemic activity in alloxan induced method 41-43 or streptozotocin-induced method 44-46 as well as acts on genetic models of diabetes 47. Moreover, a few isolated compounds like charantin, a polypeptide-p, momordin Ic, oleanolic acid 3-O-monodesmoside, and oleanolic acid 3-O-glucuronide of M. charantia also showed hypoglycemic activity 48-50.
Hypolipidemic effect: The treatment of diabetic rats with M. charantia extract resulted in significant reduction of blood lipid levels (total cholesterol and triglycerides) in diabetic rats. M. charantia also ameliorate PI-associated apoB and lipid abnormalities in HepG2 cells. Compounds in M. charantia improve lipid profiles. They reduce liver secretion of apolipoprotein B (Apo B) – the primary lipoprotein of low-density "bad" cholesterol; reduce apolipoprotein C- III expression, the protein found in very-low density cholesterol which turns into LDL/bad cholesterol; and increases the expression of apolipoprotein A-1 (ApoA1) - the major protein component of high density "good" cholesterol. It also lowers cellular triglyceride content 51.
Antioxidant effect: M. charantia extracts possess potent antioxidant and free radical scavenging activities 52-53 and this may be due to the presence of phenolic and flavonoid compounds like, galic acid, tannic acid, (+)-catechin, caffeic acid, p-coumaric, gentisic acid, chlorogenic acid and epicatechin 29-30.
Inhibition of protein Synthesis: The bitter melon plant (Momordica charantia) seeds also contain several lectins which, while not highly toxic to animals in situ, inhibit protein synthesis in vitro 54.
Hepatoprotective effect: The extract of Momordica charantia significantly reduces serum glutamic pyruvate ransaminase (SGPT), and serum glutamic oxaloacetate transaminase (SGOT) in rats. The hepatoprotective activity of M. charantia leaves may be attributed to the presence of flavonoids and ascorbic acid 55.
Antibacterial and antifungal activity: Clinically and experimentally, leaf extracts (Methanol, Ethanol and aqueous) of M. charantia have demonstrated a broad spectrum antimicrobial activity 56. Meanwhile, essential oil of the seed of M. charantia showed antibacterial and antifungal activities may due to the presence of trans-nerolidol (61.6% of the total oil) 31.
Antiviral activity: Cunnick et al., 57 clinically and experimentally demonstrated that the leaf extract of M. charantia have the ability to increase resistance against viral infections and to provide immunostimulant effects. Several isolated phytochemicals, e.g. α and β-momorcharin, lectin, MRK 29 and MAP 30, have been documented to have in vitro antiviral activity against Epstein-Barr, herpes, HIV, coxsackievirus B3 and polio-viruses and among them MAP 30 have promising anti HIV activity 58-59.
Anticancer activity: M. charantia extract and its several isolated compounds like momordin I, Id and Ie, α and β momorcharin and cucurbitacin B as well as MAP 30- have shown anticancer activity against lymphoid leukemia, lymphoma, choriocarcinoma, melanoma, breast cancer, skin tumor, prostatic cancer, squamous carcinoma of tongue and larynx, human bladder carcinomas and Hodgkin’s disease 60-67. kobori et al, 37 have depicted α-eleostearic acid present in the seed extract of this plant and its dihydroxy derivative strongly inhibited the growth of cancer and fibroblast cell lines like HL60 leukemia and HT29 colon carcinoma.
Abortifacient and antifertility activity: Literature review revealed the experimental documentation of abortifacient properties of Momordica proteins 68-72 and momorcharins produced abortifacient activity in early and midterm pregnancy 70-72.
Anti-ulcer activity: The traditional use of M. charantia in the treatment of ulcers is supported by research, suggesting the dried-powdered fruits in filtered honey have significant and dose-dependent anti-ulcerogenic activity against ethanol-induced ulcerogenesis in rats 73. Matsuda et al., 74 demonstrated momordin Ic (10 mg/kg, b.wt. p.o.) potentially inhibited ethanol induced gastric mucosal lesions.
Immunomodulatory activity: M. charantia extracts and its isolated constituents have a variable effect on the immune system. It has been shown to be immune stimulating in some studies and immunosuppressive in some conditions (allograpft rejection) 75. α- and β-momorcharin showed immunosuppressive activity via lymphocytotoxicity or to a shift in the kinetic parameters of the immune response76. However, its immunostimulant activity has been attributed to increase the interferon production and natural killer cell activity 57.
Analgesic and anti-inﬂammatory activity: Momordin Ic and its aglycone, oleanolic acid are active principles with antirheumatoid activity 77-78.
Hypotensive and anti prothrombin activity: Wang and Ng 79 observed mild hypotensive response with Momordin. In another study, M. charantia prolonged prothrombin time by inhibiting activation of factor X by factor VIIa-tissue factor complex or factor IXa 80.
Antiobesity: M. charantia and its isolated compounds increase the activity of adenosine-5-monophosphate kinase (AMPK), an enzyme that facilitates cellular glucose uptake and fatty acid oxidation. Hypoglycemic agents in M. charantia promote efficient oxidation of glucose into fuel, and conversion into starch. (Glycogen or animal starch is stored in the liver and muscle cells). During glucose shortages, fats/fatty acids are used as fuel. Continued demand for energy in the absence or shortage of glucose causes fat cells to release their fat contents to maintain energy balance. This increased fatty acid oxidation eventually leads to weight loss 81.
Toxicity and Drug interaction: The seed contains vicine and therefore can trigger symptoms of favism in susceptible individuals. In addition, the red arils of the seeds are reported to be toxic to children. Many in vivo clinical studies have demonstrated the relatively low toxicity of all parts of the M. charantia plant when ingested orally. Pregnant women should not eat bitter melon as it stimulates the uterus and may cause premature birth 82.
CONCLUSION: Recent years, ethno-botanical and traditional uses of natural compounds, especially of plant origin received much attention as they are well tested for their efficacy and generally believed to be safe for human use. It is the best classical approach on searching new molecules for management of various diseases. Thorough screening of literature available on Momordica charantia depicted the fact that it is a popular remedy among the various ethnic groups, Ayurvedic and traditional practitioners for the treatment of various ailments. Today, evidence based studies are needed to establish these facts so that these wonder drugs with lot of therapeutic activities can be traditionally use safely (excluding the toxic components) to cure the various diseases of suffering humanity with high efficacy and least side effects. Like M. charantia lot of other medicinal plants are available and the time is coming to explore the efficacy and best use of such effective secondary plant metabolites which reduce the use of synthetic modern medicine having severe side effects.
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M. Ekramul Haque*, M. Badrul Alam and M. Sarowar Hossain
PhD, Chairman, Department of Pharmacy, BRAC University, 66-Mohakhali, Dhaka-1212, Bangladesh
08 February, 2011
22 March, 2011
24 April, 2011
01 May, 2011