IngredientsMomordicosides are a group of naturally occurring cucurbitane-type triterpene glycosides (saponins) derived primarily from Momordica charantia L. (family Cucurbitaceae), a plant commonly known as bitter melon, bitter gourd, or karela. Momordica charantia is commonly known as bitter melon or bitter gourd and is widely used in Asia, Africa, and the Caribbean both as a vegetable and as a medicinal product. Bitter melon originated in Africa, where it was a dry-season staple food of ǃKung hunter-gatherers; wild or semi-domesticated variants spread across Asia in prehistory, and it was likely fully domesticated in Southeast Asia.
Momordicosides represent a special group of cucurbitacins found only in M. charantia that have a C-19 methyl group oxidized to an aldehyde. More broadly, like many other plant species of the Cucurbitaceae family, the bitter gourd contains various cucurbitane-type triterpenoids, with about 200 reported structures so far. These compounds are generally referred to as momordicosides, but also other compound names can be found, such as karavilosides, kuguacins, or goyaglycosides.
Momordica charantia contains a diverse range of cucurbitacins. Cucurbitacins represent a special class of compounds found exclusively among the members of Cucurbitaceae. The basic structure of a cucurbitacin resembles a lanostane ring 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, which is either saturated or unsaturated.
Two triterpene glycosides, momordicosides A and B, were the first to be isolated from the seeds of Momordica charantia L. (Cucurbitaceae). Their structures were determined on the basis of spectral and chemical evidence and by X-ray analysis as the 3-O-β-gentiobioside and 3-O-β-D-xylopyranosyl(1→4)-[β-D-glucopyranosyl(1→6)]-β-D-glucopyranoside, respectively, of cucurbit-5-ene-3β, 22(S), 23(R), 24(R), 25-pentaol.
Subsequent phytochemical work has uncovered a large family of named momordicoside analogues. Two bitter cucurbitacins, momordicosides K and L, and four non-bitter cucurbitacins, momordicosides F1, F2, G, and I, were isolated from the immature fruits of M. charantia. Later research identified additional congeners: momordicosides U, V, and W were isolated from M. charantia fruits, and their structures were determined to include epoxy-cucurbitane and methoxy-cucurbitane frameworks by chemical and spectroscopic methods. Momordicoside S and momordicoside T were further studied for their hypoglycemic effects in vivo, and at doses of 100 mg/kg and 10 mg/kg respectively, both compounds showed significant activity.
The cucurbitane-type triterpenoid glycosides have been named goyaglycosides, momordicosides, karavilosides, kuguaglycosides, and so forth. The bitter taste receptor TAS2R16 mediates bitter taste in response to β-glucopyranosides; the bitter principles in bitter gourd fruits, momordicosides K and L, are β-glucopyranosides of cucurbitane triterpenoids.
Bioactive compounds such as charantin, momordicin, momordine, and momordicosides G, I, and K are found in all parts of the plant, while momordenol, momordicilin, cucurbitin, and cucurbitacin are specifically extracted from the leaves. The fruit and seeds contain the highest concentration of phytochemicals, and the fruit has been reported to have the most pronounced antidiabetic activity.
The most popular ethnomedicinal preparations of the bitter gourd are karela juice, obtained by crushing and straining the unripe fruits, and cerasee, a decoction of the aerial parts of the plant. Nowadays, capsules and tablets containing powdered drug or extracts are marketed as dietary supplements and can be purchased over-the-counter and from internet suppliers.
The plant has a long history of use in Traditional Chinese Medicine (TCM), Ayurveda, and in other traditional systems. It has a long history of use in China, Ayurvedic medicine — a traditional system of healing practiced in India for over 3,000 years — and also in Okinawa, Japan. Records show that culinary and medicinal uses of bitter melon originated in India, then were introduced into Traditional Chinese Medicine practices around the 14th century.
In Ayurvedic medicine, bitter melon — known as karela — has been used for thousands of years. Its pharmacological properties are attributed to each part of the plant, including seeds, roots, leaves, and particularly the unripe fruits. Moreover, M. charantia has been used since ancient times in Traditional Chinese Medicine for treating high blood sugar and early signs of diabetes.
In various cultures including India, Turkey, Cuba, and Puerto Rico, it has been employed to treat a variety of conditions including scabies, rheumatism, liver diseases, peptic ulcers, and mood disorders. Developing countries such as Brazil, China, Colombia, Cuba, Ghana, and India have used it traditionally as a treatment for diabetes. It is also applied to treat local wounds.
Apart from its culinary use, M. charantia has a long history in traditional medicine, serving as stomachic, laxative, or anthelmintic, and most notably for the treatment of diabetes and its complications. Due to the presence of many bioactive compounds, this plant is used in folk medicine all over the world for the treatment of different pathologies, mainly diabetes, but also cancer and other inflammation-associated diseases.
Bitter melon is used in different countries as a folk medicine. The fruits are also used as a side dish in Southeast Asia. Bitter melon tea, known as gohyah or herbal tea, is made from dried slices and has been used for medicinal purposes. In India, fruits as well as leaves are used in culinary practice and as traditional treatment for diabetes, abdominal pain, and wound healing.
Momordica charantia contains a diverse array of bioactive chemical constituents, consisting of phenolic acids, flavonoids, essential oils, triterpene glycosides, fatty acids, saponins, cucurbitan-type triterpenoids, as well as a variety of proteins with different characteristics and roles. The main phytochemical constituents considered responsible for antihyperglycaemic activity include cucurbitane-type triterpenoids, karaviloside IX, different momordicosides and their aglycones, charantin, and momordicin.
The biologically active cucurbitacins, momordicosides, and steroidal glycosides from M. charantia are the main focus of current phytochemical and pharmacological research into the plant. Among the various bioactive components of M. charantia, saponins are considered major hypoglycemic agents, with more than 30 saponins demonstrating antidiabetic potential.
Among the most pharmacologically studied individual momordicosides are:
Cucurbitane-type triterpenoids possess a tetracyclic triterpene backbone with various functional groups attached, which enhance their biological activity. The structure of these compounds includes a cucurbitane skeleton with multiple hydroxyl groups and a carboxyl group, which are critical for their interaction with biological targets. Momordicosides A and M exhibited the most notable inhibitory effects in α-glucosidase assays; these two compounds were the most polar components, each possessing two glycoside moieties as well as four hydroxyl groups at positions C-22, C-23, C-24, and C-25.
The most extensively characterized molecular mechanism for the antidiabetic effects of momordicosides involves upregulation of glucose transporter 4 (GLUT4). In L6 myotubes and 3T3-L1 adipocytes, momordicosides Q, R, S, and T and karaviloside XI could enhance AMPK activity and stimulate GLUT4 translocation to the cell membrane, which is an essential step for inducible glucose entry into cells. Notably, GLUT4 translocation was mediated via AMPK phosphorylation and not via the PI3K/Akt pathway.
Tan et al. (2008) reported eight cucurbitane-type triterpenoids with enhanced GLUT4 translocation in L6 myotubes and 3T3-L1 adipocyte cells. Karaviloside XI and momordicoside S, as well as their aglycones, were the most active components, with observed effects starting at a concentration of 0.1 nM and reaching their maximum between 10 and 100 nM.
Cucurbitane-type triterpene glycosides from M. charantia showed moderate α-glucosidase inhibitory activities, with IC₅₀ values ranging from 28.40 to 63.26 μM, comparing favorably with the positive control acarbose (IC₅₀ 87.65 ± 6.51 μM). The specific mechanisms of the saponin-rich fraction also involve the activation of AMPK, promotion of GLUT4 translocation, and inhibition of α-glucosidase activity.
A saponin-rich fraction and isolated compounds from M. charantia were confirmed to stimulate insulin secretion in MIN6 β-cells. Momordicosides Q, R, S, and T increased GLUT4 translocation via the AMPK pathway in vitro, and momordicoside T improved glucose tolerance in mice fed a high-fat diet. Additionally, momordicoside U was found to be moderately active in the β-cell insulin secretion assay at concentrations of 10 and 25 μg/mL.
Momordicine I — a closely related cucurbitane aglycone — exerts an antidiabetic effect by modulating insulin signaling pathways, enhancing glucose uptake, and inhibiting glucose production in the liver. Another possible mechanism demonstrated in vivo was that bitter melon restored normal glycogen levels in insulin-dependent tissues and restored glycolytic enzyme activity levels.
Momordicine I possesses an anti-inflammatory effect via the inhibition of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-treated RAW 264.7 cells. In animal-based research, secretion levels of the spleen pro-inflammatory cytokines IL-1, IL-6, and TNF-α were significantly lower in bitter gourd-supplemented groups, while secretion levels of the IL-10 anti-inflammatory cytokine increased. Expression levels of proteins NF-κB, iNOS, and COX-2 were significantly inhibited.
The crude extract and its components prevent many types of cancers by enhancing reactive oxygen species generation; inhibiting cancer cell cycle, cell signaling, cancer stem cells, glucose and lipid metabolism, invasion, metastasis, hypoxia, and angiogenesis; and inducing apoptosis and autophagy cell death. At the molecular level, the cucurbitane triterpenoid 3β,7β-dihydroxy-25-methoxycucurbita-5,23-diene-19-al (DMC) induced apoptotic death in breast cancer cells, at least in part, through a PPARγ-dependent mechanism.
Cucurbitane-type triterpenoid glycosides are among the most distinctive metabolites of M. charantia and have been investigated for their antiviral potential. Their structural diversity, including that of momordicosides and karavilosides, has been linked to interference with viral enzymes and replication pathways.
The preclinical evidence base for momordicosides in diabetes is substantial. In animal studies, Momordica preparations were reported to increase tissue glucose uptake, liver muscle glycogen synthesis, glucose oxidation, and to decrease hepatic gluconeogenesis. Administration of M. charantia saponins (MCS) in STZ-induced diabetic mice resulted in reduction of fasting blood glucose levels and postprandial hyperglycemia.
Evidence from animal and in vitro studies indicates that bitter melon not only improves glucose metabolism but also ameliorates obesity and associated diabetic dyslipidemia. A study by Tan et al. showed that cucurbitane glycosides, momordicosides, and aglycones from bitter melon increased GLUT4 transport across membranes and activated AMPK in vitro. The study also reported that momordicoside modulated fatty acid oxidation and glucose disposal in insulin-sensitive and insulin-resistant mice.
Due to its long traditional usage, M. charantia was subjected to several studies in humans, of which only few fulfilled the criteria of a randomized controlled trial. Bitter melon is a widely used traditional remedy for hyperglycemia; while the medicinal properties of this plant have been studied extensively using in vitro and animal models, the clinical efficacy and safety in humans is largely unknown.
Early clinical reports were encouraging but methodologically limited. Four clinical trials found bitter melon juice, fruit, and dried powder to have a moderate hypoglycemic effect. These studies were small and were not randomized or double-blind, however.
More recent controlled studies show mixed results. A randomized, placebo-controlled study investigated blood glucose levels, lipid profile, and adverse events after 12 weeks of treatment with 90 subjects. There were no differences in HbA1c levels between the bitter melon extract and placebo groups; however, the average fasting glucose level of the bitter melon group decreased (p = 0.014). No serious adverse events were reported during the treatment period.
A 12-week randomized placebo-controlled clinical study investigated bitter melon extract (BME) on glucose metabolism in prediabetic patients; 33 subjects received BME and 32 received placebo. Results showed that the 75 g oral glucose tolerance test blood glucose level decreased in the BME group after 12 weeks, and the glucose level after 30 min of glucose ingestion decreased significantly. The glucagon level in the BME group after 12 weeks significantly decreased 120 min after the OGTT, suggesting that bitter melon exhibits glucose-lowering effects through suppression of glucagon levels in people with prediabetes.
A further clinical trial examined an extract standardized for the peptide constituent mcIRBP-19: a randomized, double-blind, placebo-controlled, parallel comparison study was conducted on 41 participants; groups received either placebo (300 mg starch) or 600 mg of mcIRBP-19-BGE orally for 12 weeks. The oral administration decreased fasting blood glucose (FBG; P=0.057) and HbA1c (P=0.060) with borderline significance.
A randomized, double-blind trial reported that the level of fructosamine in the blood was effectively reduced among newly diagnosed type 2 diabetes patients administered Momordica charantia fruit extract capsules (1,000 mg/day) for 1 month. Another study showed that oral bitter gourd extracts (1,000 mg/day) had a significant reduction in HbA1c in type 2 diabetic patients.
A systematic review and meta-analysis evaluated the existing evidence on the potential efficacy of bitter melon in the treatment of metabolic syndrome, based on randomized, parallel-group, placebo-controlled trials. All included trials, except two studies, were carried out in different Asian countries. Based on the nine trials included, the findings showed that M. charantia mono herbal preparations do not have a significant overall positive influence on blood glucose levels and other cardiovascular risk factors associated with metabolic syndrome. Nine studies were included in the meta-analysis with 414 patients in total and 4–16 weeks of follow-up.
Most clinical studies on bitter melon except a few were not randomized, lacked proper controls, were of short duration, used small sample sizes, and showed inconsistent findings.
Overall assessment: The preclinical evidence for momordicosides and the broader bitter melon extract in glycemic control is robust across multiple mechanistic pathways. Human clinical evidence is preliminary and inconsistent; no consensus on clinical efficacy for diabetes management has been reached based on available RCT data.
Due to the presence of many bioactive compounds, M. charantia is used in folk medicine for the treatment of inflammation-associated diseases. In cell-based research, the anti-inflammatory activity of M. charantia shows potential pharmacological value, but the abilities of the plant extract to regulate metabolism and inflammatory events in macrophages are not fully understood. Available evidence links anti-inflammatory activity with downregulation of the glycolytic pathway.
Precise mechanisms and well-controlled clinical trials of its anti-inflammatory effects have not been completely delineated.
Overall assessment: Anti-inflammatory evidence for momordicosides is confined to in vitro cell models and animal studies. No human clinical trials specifically targeting momordicosides' anti-inflammatory effects were identified; this area remains preclinical.
Bitter melon contains many bioactive components including triterpenoids, triterpene glycosides, phenolic acids, flavonoids, lectins, sterols, and proteins that show potential anticancer activity without significant side effects. The preventive and therapeutic effects of crude extract or isolated components are studied in cell line-based models and animal models of multiple types of cancer.
Bioassay-guided fractionations of an ethanol extract of M. charantia fruits led to the isolation of 15 cucurbitane-type triterpene glycosides including momordicosides I, F1, F2, K, L, and U. Biological evaluation showed that several isolated cucurbitane-type triterpene glycosides had antiproliferative activities against MCF-7, WiDr, HEp-2, and Doay human tumor cell lines.
Chemopreventive activity has been examined using the Epstein-Barr virus early antigen (EBV-EA) induction model: seventeen cucurbitane-type triterpenoids isolated from the leaves of Japanese M. charantia were examined for their inhibitory effects on EBV-EA activation in Raji cells, a known primary screening test for inhibitors of tumor promotion. Four compounds showed potent inhibitory effects on EBV-EA induction.
Many of those compounds showed anti-proliferative effects against MCF-7 (human breast adenocarcinoma), Doay (human medulloblastoma), HEp-2 (human laryngeal carcinoma), and WiDr (human colon adenocarcinoma) with IC₅₀ values ranging from 10–20 μg/mL for 72-hour treatment.
Overall assessment: Anticancer evidence for momordicosides and related cucurbitane glycosides is entirely preclinical (in vitro and animal). No human clinical trials on momordicosides as anticancer agents were identified. Findings are biologically plausible but require substantial further investigation.
Extracts obtained from the vines and leaves of bitter melon led to the isolation of fourteen cucurbitane triterpenoids, designated kuguacins F–S. These compounds were tested in vitro against HIV-1-infected cells; several showed weak antiviral activity, with EC₅₀ values ranging from 3.7 to 61 μg/mL and selectivity indices of up to 13.3.
In silico analysis showed that karaviloside III has strong inhibitory activity, and that momordicoside B, kuguaglycoside A, and cucurbitadienol also show inhibitory actions against the spike glycoprotein, main protease, and RNA-dependent RNA polymerase of SARS-CoV-2, suggesting these compounds represent candidates for further investigation; however, their actual impact on SARS-CoV-2 viral transmission remains to be determined through experimental models.
Overall, according to currently available evidence, cucurbitane-type triterpenoid glycosides from M. charantia possess in vitro activity against HIV-1 and are expected to have inhibitory effects against the influenza virus. However, further in vivo and clinical research is required to determine their pharmacological significance and therapeutic potential.
Overall assessment: Antiviral evidence is limited to in vitro and in silico work. No human clinical trials are available.
Studies have allowed the identification of a few health-promoting benefits, including hypolipidemic, hypoglycemic, and anti-obesity effects. In a murine model, M. charantia extracts (with a total content of three triterpenes at 0.69%) were shown to ameliorate the diabetic and hyperlipidemic state in high-fat-fed mice by regulating hepatic phosphoenolpyruvate carboxykinase and AMP-activated protein kinase (AMPK) phosphorylation.
Blood lipids including TG, cholesterol, and NEFA were lower in animal groups receiving bitter gourd supplementation compared to the sepsis control group.
Overall assessment: Lipid-lowering effects are demonstrated in animal models and supported by mechanistic studies. Controlled human data addressing lipid outcomes specifically attributed to momordicosides are insufficient to draw firm conclusions.
Momordicosides are not commercially available as isolated, single-compound dietary supplements; they are delivered as constituents of standardized or non-standardized M. charantia (bitter melon) preparations. Dosages reported in clinical and preclinical studies include:
Early reports mentioned charantin, a mixture of two sterol glucosides, and polypeptide p-insulin, but their low concentrations in fruits or limited bioavailability cannot fully explain the observed therapeutic effects. No regulatory agency (e.g., FDA, EMA, WHO) has established an approved standardized dose specifically for momordicosides as isolated compounds.
Reported adverse effects of bitter melon include hypoglycemic coma and convulsions in children, reduced fertility in mice, a favism-like syndrome, increases in gamma-glutamyltransferase and alkaline phosphatase levels in animals, and headaches.
In a 3-month RCT (n=40), adverse events with 3 g/day bitter melon capsules included diarrhea and abdominal pain; serum ALT and AST declined slightly in both groups.
No mortality or toxicity were observed in rats treated with a single dose of a bitter melon seed extract (scCO₂ extraction) during a 14-day observation period. The median lethal dose (LD₅₀) of the extract was considered greater than 2,000 mg/kg body weight. In the sub-chronic toxicity study, male and female rats were orally administered daily doses of 0, 250, 500, and 1,000 mg/kg body weight for 90 days; no mortality, morbidity, or abnormal pathological and biochemical alterations were observed.
Bitter melon may have additive effects when taken with other glucose-lowering agents. Momordica charantia has demonstrated hypoglycemic effects in various studies, yet its interactions with pharmaceutical antidiabetic agents remain poorly understood. Molecular docking and in silico predictive analyses have been used to explore potential herb-drug interactions between M. charantia phytoconstituents (including cucurbitane triterpenoids) and pharmaceutical antidiabetic drugs, though these remain theoretical at present.
Adequately powered, randomized, placebo-controlled trials are needed to properly assess safety and efficacy before bitter melon can be routinely recommended. Bitter melon may have hypoglycemic effects, but data are not sufficient to recommend its use in the absence of careful supervision and monitoring.
Many animal trials have demonstrated that the extract of Momordica charantia and its ingredients are beneficial in lowering blood glucose; however, results in human trials are not consistent. These compounds exhibit hypoglycaemic effects in animals that mimic human prediabetic and diabetes status, but the translatability of the above evidence in clinical settings is not properly validated.
Health conditions that Momordicosides may help support.
Body systems that Momordicosides may help support.
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