Charantin

Charantin

1. Identity: Chemical and Botanical Profile

1.1 Chemical Identity

Charantin is a 1:1 mixture of two steroidal saponins, β-sitosteryl glucoside (C₃₅H₆₀O₆) and 5,22-stigmasteryl glucoside (C₃₅H₅₈O₆). Some literature additionally describes charantin as a cucurbitane-type triterpenoid; charantin, a natural cucurbitane-type triterpenoid, has been reported to have beneficial pharmacological functions such as anticancer, antidiabetic, and antibacterial activities. These two characterizations reflect the fact that multiple structurally related classes of compound have been grouped under the "charantin" label in the literature, and charantin, a steroidal glycoside, exists as a mixture of stigmasterol glucoside (STG) and β-sitosterol glucoside (BSG) in the fruits of Momordica charantia.

It is a whitish crystalline substance, neutral and tasteless, melting at 266–268 °C, and is sparingly soluble in water or other highly polar solvents. It is obtained from the Asian bitter melon (Momordica charantia), and is reputed to be responsible for the hypoglycaemic properties of that plant. It was identified by Lolitkar and Rao in 1960. It was also found in the similar African species M. foetida by A. Olaniyi in 1975, under the name foetidin.

1.2 Botanical Source

The primary botanical source is Momordica charantia L. (family Cucurbitaceae), commonly known as bitter gourd or bitter melon, which is widely cultivated in many tropical and subtropical regions of the world, where its unripe fruits are eaten as a vegetable. It grows in tropical areas of the Amazon, East Africa, Asia, India, South America, and the Caribbean, and is used traditionally as both food and medicine. The plant is a climbing perennial with elongated fruit that resembles a warty gourd or cucumber.

Most biosynthetic genes related to charantin production are highly expressed in flowers and/or fruit from the ripening stages. HPLC analysis has confirmed that the accumulation of charantin is highest in fruits from the ripening stage, followed by male flowers. At the tissue level, charantin is present in large quantities in flesh parts, while vicine is mainly concentrated in the whole fruit containing seeds.

1.3 Common Forms and Preparations

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. Charantin-containing preparations are also sold as standardized extracts specifying a minimum percentage of bitter principle. In research contexts, charantin has been isolated using ethanol, methanol, and pressurized liquid extraction, and characterized by thin-layer chromatography (TLC), Fourier-transform infrared spectroscopy (FTIR), and HPLC-DAD methods.

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2. Traditional and Historical Use

2.1 Geographic Traditions and Time Periods

Momordica charantia has a long history of human use in traditional medicine throughout the world. It is widely used in Asia, Africa, and the Caribbean as a vegetable as well as a medicinal product, and has a long history of use in Traditional Chinese Medicine (TCM), Ayurveda, and in other traditional systems. Specifically, M. charantia has been used since ancient times in Traditional Chinese Medicine for treating high blood sugar and early signs of diabetes.

Traditional uses extended well beyond glycemic management. 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. According to the Unani system of medicine, the fruit is described as very bitter, carminative, tonic, stomachic, aphrodisiac, anthelmintic, and astringent to the bowels, and useful in treatment of syphilis, rheumatism, and spleen troubles.

The fruit, leaves, and seeds of bitter melon have traditionally been used as medicinal herbs for anti-HIV, anti-ulcer, anti-inflammatory, anti-leukemic, antimicrobial, anti-diabetic, and anti-tumor purposes. According to Ayurveda, the roots are useful in the treatment of eye-related diseases. In the 1980s, the seeds were investigated in China as a potential contraceptive.

2.2 Preparations Used Traditionally

Across traditional systems, preparations have typically been made from the unripe (green) fruit, leaves, seeds, and roots of the plant. Preparations included fresh juice from crushed fruit (karela juice), decoctions of aerial parts (cerasee tea in the Caribbean), powdered dried fruit, and infusions of leaves. Unripe fruit, seeds, and aerial parts of Momordica charantia have been used in various parts of the world to treat numerous health problems, including diabetes. Oral administration of the fruit juice or seed powder causes a reduction in fasting blood glucose and improves glucose tolerance in normal and diabetic animals and in humans.

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3. Key Constituents and Active Compounds

3.1 Charantin in the Context of M. charantia Phytochemistry

Charantin is one among many bioactive compounds found in bitter melon. Blood glucose regulation is linked to the following substances: charantin (a mixture of steroidal saponins), polypeptide-p, vicine, and momordin analogs (e.g., momordinol, momordicilin, momorcharin, and momordicin). Bitter melon seeds, leaves, berries, and fruit peels contain about 228 components. It is rich in vitamins A, B1, B2, B9, C, and E, and minerals such as calcium, potassium, zinc, magnesium, phosphorus, and iron, and has abundant bioactive substances including anthraquinones, essential oil, saponin, triterpenes, alkaloids, and momordicine.

Bioassay-guided fractionations have attributed the anti-diabetic benefits of M. charantia to a mixture of steroidal saponins (e.g., charantin), the alkaloid vicine, polypeptide-p (also known as plant insulin), and other cucurbitane-type triterpenoids. Charantin, identified as a saponin and cucurbitane-type triterpenoid isolated from bitter melon, is one of the major compounds identified as a hypoglycemic agent.

3.2 A Note on Nomenclature Complexity

The term "charantin" in the literature has been applied inconsistently. It has variously denoted: (a) the classical 1:1 steroidal glucoside mixture (β-sitosteryl glucoside + stigmasteryl glucoside) described by Lolitkar and Rao; (b) broader cucurbitane-type triterpenoid fractions of M. charantia that exhibit hypoglycemic activity; and (c) a separate ribosome-inactivating peptide isolated from bitter melon seeds that is also named "charantin" in the peptide literature. Researchers and reviewers do not always distinguish between these uses, which complicates interpretation of the evidence base.

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4. Mechanisms of Action

4.1 Glucose Metabolism and Insulin Signaling

Charantin has been shown to have insulin-like activity by augmenting insulin release, reducing gluconeogenesis, increasing hepatic glycogen synthesis, and increasing peripheral glucose oxidation. Antidiabetic activity could be confirmed for charantin, but not for steroidal saponin aglycones, indicating that the glycoside moiety is essential for observed activity.

Phytochemical analyses of M. charantia reveal its rich composition of cucurbitane-type triterpenoids, saponins (charantin), peptides, and polysaccharides, which collectively contribute to its hypoglycemic effects. In vitro studies demonstrate that these compounds enhance glucose uptake in skeletal muscle cells via AMP-activated protein kinase (AMPK) activation, inhibit α-glucosidase activity, and protect pancreatic β-cells from oxidative stress.

Treatment with M. charantia extracts decreased plasma insulin and increased insulin sensitivity by increasing the expression of GLUT4 in the skeletal muscle and of IRS-1 in the liver of mice with type 2 diabetes. 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 action.

Additional mechanisms operating at the intestinal level include inhibition of carbohydrate-digesting enzymes. An inhibitory effect on α-glucosidase by cucurbitane-type triterpene glycosides isolated from Momordica charantia fruit has also been reported. Experimental findings in alloxan diabetic rats suggest that bitter melon extract enhances insulin secretion by the islets of Langerhans, reduces glycogenesis in liver tissue, enhances peripheral glucose utilization, and increases serum protein levels.

4.2 Lipid Metabolism

Charantin, a plant-based natural compound known for its diverse pharmacological properties, has been investigated for its anti-hyperlipidemic activity using both in-silico and in-vivo approaches. Molecular docking studies have assessed charantin's binding interactions with key lipid-regulating proteins, including HMGCR, PCSK9, LDLR, PPAR-α, and PI3K. In a high-lipid diet animal model, charantin significantly reduced total cholesterol, triglycerides, LDL, and VLDL, while increasing HDL levels in a dose-dependent manner. Liver function remained preserved, accompanied by downregulation of HMGCR, PCSK9, and APOB, and upregulation of LDLR and PPAR-α at both gene and protein levels.

In old obese rats, a standardized M. charantia extract demonstrated significant lowering of cholesterol and triglyceride levels while elevating HDL-cholesterol levels. The extract also lowered serum lipids in alloxan diabetic rats, suggesting its usefulness in controlling metabolic alterations associated with diabetes.

4.3 Antioxidant and Anti-inflammatory Activity

The chemical constituents present in bitter melon help in minimizing oxidative damage by neutralization of free radical activity and performing prompt actions to control the death of β-cells. Studies have reported that bitter melon significantly increased insulin production and decreased glucagon production, suggesting that bitter melon acts directly on β-cells and enhances them due to its antioxidant properties.

4.4 Antimicrobial Activity

Studies have confirmed antimicrobial activity of charantin when compared with standard antibiotics, against bacterial species including gram-positive (Bacillus subtilis), gram-negative (Pseudomonas aeruginosa), and fungal strains. This work remains largely confined to in vitro agar diffusion assays and has not been evaluated in clinical trials.

4.5 Anticancer Activity

Isolated components of M. charantia, including charantin, have been identified as having effective biological activities. The antitumor activity of bitter melon extract was initially validated in mice in 1983. Bitter melon extract or its isolated ingredients have demonstrated noteworthy anticancer activity against skin, prostate, breast, colon, bladder, and pancreatic cancers in several preclinical investigations. All such findings, as of current evidence, are limited to in vitro cell studies and animal models; no clinical trials have evaluated charantin in isolation for cancer treatment.

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5. Scientific Evidence by Area of Use

5.1 Glycemic Control and Type 2 Diabetes

Animal and In Vitro Evidence

The charantin-rich fraction of M. charantia reduced blood sugar levels in type 1 and type 2 diabetic animal models. In rat studies using the Sprague-Dawley model, normal and hyperglycemic rats were fed on skin, flesh, and whole fruit of bitter melon at 150 and 300 mg/kg body weight and assessed for diabetes prophylaxis and treatment. The most potent dose was 300 mg/kg whole fruit, which resulted in 31.64% lowering of blood glucose level and 27.35% increase in insulin level in hyperglycemic rats.

An important limitation was identified in a 2021 PMC study: current research suggests that individual phytochemicals like charantin or vicine are less effective in diabetes management. The complex interaction of these hypoglycemic agents of bitter melon can play a more operative role in delaying the pathogenesis of diabetes mellitus.

Human Clinical Evidence

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. The clinical evidence specifically for isolated charantin is largely absent; human trials have predominantly studied whole bitter melon preparations (juice, powder, extract, or capsules) rather than purified charantin.

A 12-week, randomized, placebo-controlled study examined the effects of bitter melon extract (BME) in Korean adults with prediabetes. A total of 76 participants were randomly assigned. In the final analysis, 33 and 32 subjects were included in the BME and placebo groups, respectively. Results showed that 75 g oral glucose tolerance test (OGTT) blood glucose level decreased in the BME group after 12 weeks. The glucose level after 30 minutes of glucose ingestion decreased significantly. The glucagon level in the BME group after 12 weeks significantly decreased 120 minutes after 75 g OGTT. These results suggested that bitter melon exhibits glucose-lowering effects through suppression of glucagon levels in people with prediabetes.

A randomized, double-blind, placebo-controlled trial evaluated a specific bitter melon peptide fraction. Subjects were randomly assigned to two groups: a treatment group (N = 20) and a placebo group (N = 20), orally administered 600 mg of the extract preparation. The oral administration of this extract decreased with borderline significance at fasting blood glucose (FBG; P=0.057) and HbA1c (P=0.060), indicating that results did not achieve statistical significance.

Systematic Reviews and Meta-Analyses

The findings across clinical studies are contradictory. A 2023 systematic review and meta-analysis searched Embase, Cochrane, PubMed, and Web of Science databases for randomized controlled human trials, reporting according to the PRISMA statement. Studies included varied in length between 4 and 16 weeks; the sample size was low (24–90 participants); the study drugs were inconsistent in quality (dry plant material and dry extracts) and in quantity (the daily dose was 2–6 g fruit or extract equivalent to 9 g fruit). The total number of participants was 414, from different Asian or North American countries. The review concluded that the metabolic effect of M. charantia cannot be determined based on the available clinical evidence.

A 2024 GRADE-assessed systematic review and meta-analysis included a total of eight trials involving 423 patients with T2DM. The study examined the impact of M. charantia intake on glycemic indexes and the lipid profile of patients with T2DM.

Although Momordica has shown promising results in preclinical studies, the existing quantitative synthesis of evidence reports contradictory findings. Studies have aimed to evaluate the effect of Momordica charantia on fasting blood glucose (FBG), glycated haemoglobin (HbA1c), insulin, homeostatic model of insulin resistance (HOMA-IR), and homeostatic model of β-cell function (HOMA-β) in individuals with prediabetes or T2D.

Clinical studies following double-blind randomized controlled trials on human subjects must be conducted to warrant their use in humans. The current consensus in the literature is that the evidence for whole bitter melon preparations is mixed and methodologically weak, and that for isolated charantin specifically, this compound has not yet been clinically investigated for treating diabetes.

5.2 Lipid Profile and Cardiovascular Metabolic Parameters

Charantin exerts lipid-lowering effects through modulation of multiple pathways, including cholesterol biosynthesis, lipoprotein metabolism, and nuclear receptor activation — based on in-vivo data. In-vivo efficacy of charantin at doses of 100 and 200 mg/kg was evaluated in Sprague-Dawley rats fed a high-lipid diet for 12 days. These results are limited to animal models with no corroborating human clinical data for isolated charantin.

5.3 Anticancer Effects

Charantin has been reported to have beneficial pharmacological functions such as anticancer, antidiabetic, and antibacterial activities, but anticancer evidence is confined entirely to in vitro and preclinical animal studies. No human clinical trials have examined charantin's anticancer effects. Charantin is one of several bioactive components of M. charantia that has demonstrated cancer-relevant activity in cell-based assays, including against breast, colon, prostate, bladder, and pancreatic cancer cell lines, with effects attributed to apoptosis induction, cell-cycle arrest, and oxidative stress modulation. These findings must be characterized as preliminary.

5.4 Antimicrobial Effects

Antimicrobial activity has been demonstrated for charantin in in vitro agar diffusion studies. Isolated charantin has been characterized with the help of ultraviolet spectroscopy, thin-layer chromatography, FTIR, mass spectroscopy, and proton-NMR spectroscopy, confirming identification. The antibacterial activity of charantin was tested by using the agar diffusion (cup plate) method. These data have not been translated into human studies.

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6. Body Systems and Health Areas Associated with Charantin

• Endocrine and metabolic system: Blood glucose regulation, insulin secretagogue and insulin-sensitizing effects, glycogen synthesis, modulation of gluconeogenesis, and management of hyperglycemia in diabetes mellitus (type 1 and type 2) and prediabetes.
• Cardiovascular and lipid metabolism: Reduction of total cholesterol, triglycerides, LDL, and VLDL, and elevation of HDL in animal models.
• Gastrointestinal system: Historically used as a stomachic, laxative, and anthelmintic across traditional medicine systems.
• Hepatic system: Involvement in hepatic glycogen synthesis and gluconeogenesis regulation; liver function has been found to remain preserved in animal studies using charantin at 100–200 mg/kg.
• Musculoskeletal (glucose uptake): Enhancement of glucose uptake in skeletal muscle cells via AMPK activation in in vitro studies.
• Oncology (preclinical): Cell-based and animal evidence for activity against multiple cancer types, without clinical validation.
• Infectious disease (preclinical): In vitro antibacterial and antifungal activity demonstrated.
• Reproductive system (safety consideration): Cucurbitane-type triterpenoids from M. charantia have partial agonist/antagonist activity for estrogen receptor α and β, and could be partly responsible for interference in the reproductive hormone signaling pathway and may be associated with infertility-inducing adverse effects of this fruit.

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7. Dosage Forms and Dosages Reported in Studies

Charantin has not been established in any standardized clinical dosing regimen for human use. Dosages in the available literature pertain primarily to whole bitter melon preparations containing charantin as one of multiple bioactive constituents, not to isolated charantin.

• Animal studies: Bitter melon was administered to normal and hyperglycemic Sprague-Dawley rats at doses of 150 and 300 mg/kg body weight. In-vivo efficacy of charantin specifically was evaluated at 100 and 200 mg/kg in Sprague-Dawley rats fed a high-lipid diet for 12 days.
• Human RCTs (whole bitter melon): In randomized clinical trials identified in systematic review, the daily dose was typically 2–6 g of fruit or extract equivalent to 9 g fruit; study duration varied between 4 and 16 weeks.
• Human RCT (extract preparation): Subjects in one randomized controlled trial were orally administered 600 mg of a mcIRBP-19-containing bitter gourd extract.
• Supplement formulations (as described in review literature): 500 mg capsules, each containing 200 mg Momordica extract standardized to 2.5% bitter principle and 300 mg dried fruit powder, have been used in some clinical trials.
• Drug interaction studies: In a clinical trial, a chloroform/benzene karela extract (400 mg) co-administered with metformin or glibenclamide (at 50% of clinical doses) produced a greater hypoglycemic effect compared to full doses of either antidiabetic agent alone.

No regulatory body (FDA, EMA, WHO) has established an approved dose or daily reference intake for charantin as an isolated compound.

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8. Safety Considerations and Interactions

8.1 General Tolerability

Bitter melon (Momordica charantia) is widely studied in animals and modestly in humans for safety. Most human data, at up to approximately 6 g/day of typical preparations, do not show clear liver or kidney harm, but several animal studies reveal microscopic organ changes at higher or repeated doses.

8.2 Hypoglycemia Risk

The most clinically significant safety concern with charantin-containing preparations is excessive blood glucose lowering. Comas and convulsions in children due to hypoglycemia, as well as paroxysmal atrial fibrillation, have been reported in association with bitter melon use. This risk is heightened when bitter melon preparations are taken alongside pharmaceutical antidiabetic agents.

8.3 Drug Interactions

An increased hypoglycemic effect with co-administered pharmaceutical agents, such as hypoglycemic medications, has been postulated. In a clinical trial, a chloroform/benzene karela extract (400 mg) co-administered with metformin or glibenclamide (at 50% of clinical doses) produced a greater hypoglycemic effect compared to full doses of either antidiabetic agent alone.

Minor effects on cytochrome P450 enzymes and glutathione S-transferase were observed in one experiment, which may have implications for metabolism of co-administered drugs. An interaction between bitter melon and pazopanib has been reported, whereby bitter melon may enhance the adverse or toxic effect of pazopanib, specifically with an increased risk of pancreatitis.

Momordica charantia has demonstrated hypoglycemic effects in various studies, yet its interactions with pharmaceutical antidiabetic agents remain poorly understood.

8.4 Reproductive and Teratogenic Toxicity

Bitter melon is contraindicated during pregnancy because of the high risk of miscarriage. Cucurbitane-type triterpenoids from M. charantia have partial agonist/antagonist activity for estrogen receptor (ER) α and β, and could be partly responsible for interference in the reproductive hormone signaling pathway and may be associated with infertility-inducing adverse effects of this fruit.

8.5 Hepatic and Renal Toxicity

Animal studies show that bitter melon can cause testicular, liver, and kidney toxicity at higher or prolonged doses, while human studies report no serious short-term adverse effects. The principal toxicity of Momordica charantia in animals is to the liver and reproductive system. These effects have not been reported in humans despite widespread use of the fruit medicinally and as a vegetable.

In one acute and sub-chronic toxicity study using bitter melon seed extract in Wistar rats, pathological examination did not reveal any significant findings, and microscopic lesions were considered spontaneous and incidental. Importantly, pathological examination did not reveal histomorphological alterations in the seminiferous tubules and prostate of male rats observed in previous reproductive studies.

8.6 Limitations of the Safety Evidence Base

Nearly all safety data relate to whole bitter melon preparations rather than to isolated charantin. Given that other reported hypoglycaemic principles from Momordica charantia include the sterol glucoside mixture charantin and the pyrimidine nucleoside vicine, and these are only effective at doses too high to account for all the activity of the plant extract, the pharmacological and toxicological properties of the isolated compound may differ from those of the whole plant or crude extract. The safety profile of purified charantin administered to humans has not been formally established.

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9. Summary Assessment of Evidence Strength

The majority of evidence supporting charantin's bioactivities derives from in vitro cell studies and animal models. The strongest body of preclinical evidence pertains to glucose-lowering mechanisms, lipid modulation, and AMPK-mediated effects in skeletal muscle and hepatic tissue. Human clinical evidence exists for whole M. charantia preparations (juice, powder, extracts), but isolated charantin has not been subjected to human clinical trials. Systematic reviews and meta-analyses of bitter melon preparations in humans have consistently found the evidence to be mixed and limited by small sample sizes, short study durations, and heterogeneous preparations. Any claim that charantin specifically produces a defined clinical effect in humans is not yet supported by the current body of evidence.

References

• Wikipedia — Charantin
• Accumulation of Charantin and Expression of Triterpenoid Biosynthesis Genes in Bitter Melon (Momordica charantia) — PubMed (2017)
• Isolation, characterization and quantitative HPLC-DAD analysis of components of charantin from fruits of Momordica charantia — ScienceDirect (2020)
• Bitter Melon Fruit Bioactives Charantin and Vicine Potential for Diabetes Prophylaxis and Treatment — PMC (2021)
• Momordica charantia L. — Diabetes-Related Bioactivities, Quality Control, and Safety Considerations — PMC / Frontiers in Pharmacology (2022)
• Comprehensive Studies on the Regulation of Type 2 Diabetes by Cucurbitane-Type Triterpenoids in Momordica charantia L. — MDPI Pharmaceuticals (2025)
• Momordica charantia Efficacy and Safety on Glucose Metabolism in Korean Prediabetes Participants: A 12-Week, Randomized Clinical Study — PMC (2023)
• A Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Hypoglycemic Efficacy of mcIRBP-19-Containing Momordica charantia Fruit Extracts in Type 2 Diabetic Subjects — PMC (2022)
• The Metabolic Effect of Momordica charantia Cannot Be Determined Based on the Available Clinical Evidence: A Systematic Review and Meta-Analysis of Randomized Clinical Trials — PMC / Frontiers in Nutrition (2023)
• Effects of Momordica charantia L. Supplementation on Glycemic Control and Lipid Profile in T2DM Patients: A Systematic Review and Meta-Analysis of RCTs — Heliyon / ScienceDirect (2024)
• Clinical Application of Momordica charantia (Bitter Melon) for Reducing Blood Sugar in Type 2 Diabetes Mellitus — PMC (2023)
• Promise of Bitter Melon (Momordica charantia) Bioactives in Cancer Prevention and Therapy — PMC (2016)
• Momordicine I Suppresses Glioma Growth by Promoting Apoptosis and Impairing Mitochondrial Oxidative Phosphorylation — PMC (2023)
• Charantin Targets HMGCR-PCSK9 Axis and Activates PPAR-α Signaling to Ameliorate Hyperlipidemia — PMC (2025)
• An Experimental Evaluation of the Antidiabetic and Antilipidemic Properties of a Standardized Momordica charantia Fruit Extract — BMC Complementary Medicine and Therapies (2007)
• Evaluation of Acute and Sub-Chronic Toxicity of Bitter Melon Seed Extract in Wistar Rats — PMC (2022)
• Lower Hypoglycemic but Higher Antiatherogenic Effects of Bitter Melon than Glibenclamide in Type 2 Diabetic Patients — PMC (2015)
• Molecular Docking and In Silico Predictive Analysis of Potential Herb-Drug Interactions Between Momordica charantia and Miglitol — PMC (2025)
• Isolation, Characterization and Antimicrobial Activity of Charantin from Momordica charantia Linn. Fruit — ResearchGate
• Efficacy of Momordica charantia in Glycaemic Control and Insulin Resistance Among Patients with Prediabetes and Type 2 Diabetes: A GRADE-Adherent Meta-Analysis of Randomised Controlled Trials — PMC (2025)