Momordica charentia

Bitter melon - The melon that combats diabetes

Diabetes mellitus has been well recognised as a disease in India since the Sixth Century BC, and was even distinguished into two types, one genetically based and the other resulting from dietary indiscretions - today known respectively as Type 1 and Type 2 diabetes.1 The traditional Indian Ayurvedic, Unani, and Siddha systems of herbal medicine describe more than 100 medicinal plants as being beneficial for diabetes.

Bitter melon (Momordica chrantia), also known as bitter gourd, African cucumber, or wild cucumber, is a climbing plant of the family Cucurbitaceae. Its genus name, Momordica, means 'to bite', and refers to the jagged edges of the plant's leaf, which have a bitten appearance, while the species name charantia derives from the Greek word for beautiful flower.

M. charantia grows in tropical areas of Asia, the Amazon region of South America, Africa, and the Caribbean. Its oblong fruit resembles a small cucumber and is typically about 5 cm long on the wild plant, but grows to as long as 25 cm on cultivated plants. The young, emerald green fruit becomes orange-yellow upon ripening.

Although the entire plant including the fruit has a bitter taste, the fruit of M. charantia is widely used as a vegetable, and is known in Hindi as karela, in the Philippines as ampalaya, and in the West African country of Togo as guingbe. It is generally fried or cooked in water and eaten whole.

Throughout India, Asia, Africa, and South America, however, the fruit and leaves of bitter melon also have time-honored use as a medicine. Besides being used for treating diabetes, the fruit, leaves, seeds, and roots of the plant have also been used to treat a wide range of other conditions, including intestinal colic, peptic ulcers, parasitic worm infestations, malaria, constipation, dysmenorrhea, eczema, gout, jaundice, kidney stones, leprosy, leucorrhea, piles, pneumonia, psoriasis, rheumatism, chickenpox, measles, and scabies. The leaves are commonly used to make a decoction in which they are boiled in 3 cups of water, which is then further boiled until reduced to 1 cup. This decoction is taken from one to three times daily. The fruit is often dried and taken in the form of a powder, or as a dried water or alcohol extract in tablet or capsule form. Bitter melon is also used externally for the rapid healing of wounds.

Phytochemistry

Active constituents of M. charantia include glycosides, saponins, alkaloids, fixed oils, triterpenes, proteins, and steroids. These constituents are concentrated in the fruit of the plant, which has been shown to be the part of the plant with the most pronounced hypoglycemic activity.2 Several other phytochemicals, including cucurbitins, cucurbitacins, momorcharins, momordenol, and momordicins ― identified as important for their nematocidal activity3 — have also been isolated from bitter melon. Besides this, the plant contains a group of proteins designated MRK29 that inhibit human immunodeficiency virus (HIV), and inhibitors of trypsin, elastase, and guanylate cyclase, as well as lectins.2

Anthelmintic, antiviral, and antimicrobial activities

Extracts of various parts of the bitter melon plant, including the leaf, fruit, and seeds have been investigated and found to be pharmacologically active against microbes. The leaf extract and a fruit extract, in addition to whole-plant extracts, have shown antimicrobial and antiviral activities. Isolated constituents, including alpha-momorcharin, have been shown to have anti-HIV activity, and ribosome-inactivating proteins of M. charantia have shown activity against both herpes and polio viruses.2 Additionally, in vitro studies have identified an anthelminthic activity against the worm Ascaridia galli.4

Antineoplastic activity

Various preliminary studies, both in vitro and in vivo, have found antineoplastic activity in crude extracts and purified fractions of M. charantia.2 In a two-step model of skin carcinogenesis in mice, oral administration of an aqueous extract of the fruit of M. charantia protected against the development of skin tumors and increased life expectancy. The extract also reduced carcinogen-induced lipid peroxidation in the liver and DNA damage in lymphocytes, and significantly activated hepatic glutathione-S-transferase, glutathione-peroxidase, and catalase, all of which had become functionally depressed by exposure to the carcinogen used in the study.5 The results of this study suggest a potentially prophylactic role against carcinogenesis of water-soluble constituents of bitter melon fruit, possibly mediated by their modulatory effect on enzymes involved in the biotransformation and detoxification of xenobiotic substances.5 The clinical significance of these findings remains to be determined.

Antiulcerative and immunomodulatory activity

The traditional use of bitter melon for treating gastrointestinal ulcers is supported by research suggesting that the dried-powdered fruits of the plant, administered in filtered honey, have significant and dose-dependent activity against ethanol-induced ulcerogenesis in rats.2 Antiviral activity against H. pylori would further contribute to this protective effect of M. charantia.2

Various studies have found both immunostimulating and immunosuppressive effects of extracts and isolated constituents of bitter melon.2 Any clinical significance of this is likely to be highly dependent on the type of extract or constituent, its, dosage, and its route of administration. However, the immunomodulatory activity of bitter melon may explain its traditional use in psoriasis, a known autoimmune disorder.

Alloxan-induced diabetes

The antihyperglycemic activity of bitter melon - present in the fruit, seed, leaf, and whole plant, and confirmed in animal studies2 - has been its most studied and most significant medicinal property.

Diabetes mellitus can be induced in animals by partial pancreatectomy or by the administration of diabetogenic drugs such as alloxan, streptozotocin, dithizone, and anti-islet-cell antibodies, which selectively destroy the β-cells of the islets of Langerhans. Alloxan, an oxidised product of uric acid, is one of the most commonly used agents for creating experimental models of diabetes.

A study of the hypoglycemic effects of the 30 most popular anti-diabetic herbs in Indian traditional medicine in rats with alloxan-induced diabetes found M. charantia to be the most potent. In this study a dose of 250 mg/kg of a dry ethanolic extract given for two weeks reduced blood glucose from a baseline level of 244 mg/dl to 119 mg/dl.6 No sugar was detected in the animals' urine at the end of the treatment period.6

Another study confirmed that both alcoholic and aqueous extracts of bitter melon fruit had hypoglycemic effects in a rat model of acute alloxan-induced diabetes.7 In this study, in which various dosages of both extracts significantly reduced blood sugar levels after 1 week of treatment, a maximum hypoglycemic effect was observed after three weeks of treatment with a freeze-dried, lyophilised aqueous extract of the fruit at 200 mg/kg daily. In rats with chronic alloxan-induced diabetes, a 200 mg/kg daily dose of the lyophilised extract reduced plasma glucose levels by 64% within one month, which increased to a 70% reduction after four months.7

A third recent study of the antihyperglycemic effects of bitter melon used three different extracts of green, unripe fruits of the plant: a methanolic extract of the dried fruit, a chloroform extract of the dried fruit, and a water extract prepared from the fresh fruit, all three of which were subsequently freeze-dried to yield powders. The study compared the powdered extracts, each fed orally at a dosage of 20 mg/kg, with a dosage of 0.1 mg/kg glibenclamide, a drug used in treating Type 2 diabetes, for their antihyperglycemic effects in rats with alloxan-induced diabetes. All three extracts reduced the animals' blood glucose levels, with the water extract proving most effective and comparable to glibenclamide, and the chloroform extract having the most minimnal effect, as shown in Table 1.8

Streptozotocin-induced diabetes

In rats with streptozotocin-induced diabetes - a model of human insulin-dependent diabetes - bitter melon has been shown to improve glucose tolerance significantly. In a study in which it was compared with metformin, 500 mg/kg of an alcoholic extract of bitter melon reduced plasma glucose levels by 26% at 3.5 hours after dosing, a highly significant reduction, versus a 40% to 50% reduction with 200 mg/kg metformin.9 The study also suggested that bitter melon reduces plasma glucose levels partly by stimulating glycogen synthesis in the liver rather than by acting as an insulin secretagogue.9

In a study of streptozotocin-induced diabetes in mice, bitter melon extract reduced plasma glucose levels by about 22.7% after 2 months of administration. Administration of the extract led to a 36% increase in both hepatic and skeletal muscle glycogen content and a 5% decrease in renal glycogen content, suggesting that bitter melon can increase glucose utilization and glycogen formation.7 The extract also partly restored hepatic glucokinase, hexokinase, glucose-6-phosphate, and phosphofructokinase levels in the diseased animals.7

These findings suggest that bitter melon is more effective when there remains some functional responsiveness of pancreatic beta-cells in diabetes, but that it can produce a hypoglycemic effect even when this is not the case, indicating that bitter melon may have a direct insulin-mimetic effect.7

Effects on hyperglycemia with hypercholesterolemia

An Indian study compared the effects of a water extract of bitter melon at a dose of 20 mg/kg with those of glibenclamide on liporotein and cholesterol levels in diabetic rats. Although neither treatment changed the animals' total or high-density lipoprotein (HDL) cholesterol levels HDL levels, bitter melon reduced their triglyceride levels by 69%, versus 65% for glibenclamide, and both treatments reduced the animals' elevated levels of very-low-density lipoproteins (VLDL).8

In another study, of rats given either a cholesterol-free or a cholesterol-enriched diet, 14 days of dosing with freeze-dried powdered bitter melon fruit increased serum HDL-cholesterol and consistently reduced hepatic triglyceride and total cholesterol concentrations in both groups.10 Interestingly, however, bitter melon consistently reduced blood glucose concentrations only in the rats fed the cholesterol-free diet, indicating that its efficacy may depend on a low-cholesterol diet.10

Prevention of diabetic complications

As might be expected, the antihyperglycemic effects of bitter melon are likely to be linked to a reduction or delay in complications of diabetes. In controlled studies of mice with streptozotocin-induced diabetes, bitter melon has been found to reduce levels of serum creatinine and urine albumin, as well as urine volume and renal weight.11 It has also shown efficacy in preventing cataracts in mice with alloxan-induced diabetes.12

Through its antihyperglycemic and antihyperinsulinemic effects,2 bitter melon extract may also reduce the risk of metabolic syndrome, or 'Syndrome X,' which is characterised by a group of metabolic risk factors for type 2 diabetes and cardiovascular disease including central obesity, atherogenic dyslipidemia, and insulin resistance or glucose intolerance.

Clinical studies

Clinical studies with bitter melon are few and suffer from poor methodology, small numbers of subjects, and poorly defined preparations of M. charantia. Nevertheless, they do tend to confirm the traditional use of bitter melon in treating diabetes. Among findings in these human studies were reductions in blood glucose levels in nine patients with Type 2 diabetes, as reflected by an oral glucose tolerance test (50 g), an improvement in glucose tolerance in diabetic subjects without an accompanying increase in serum insulin levels, and significant reductions in postprandial serum glucose and fasting glucose in 5 patients with moderate Type 2 diabetes.2

The antihyperglycemic and related effects of bitter melon are summarised in Table 2. Although its most significant activity remains undetermined, it has not been found to increase insulin levels. Its antihyperglycemic activity is likely to be related to such extrapancreatic effects as promoting glucose storage in muscle and liver while suppressing excessive hepatic glucose synthesis. This would make it similar in effect to metformin, and this similarity has been suggested.13

Safety

In rats with alloxan-induced diabetes, a water extract of bitter melon given over a 4 week period did not appear to increase levels of uric acid or creatinine, suggesting an absence of any significant nephrotoxic effect.8 The study investigators concluded that the extract could be safely prescribed to diabetic patients.8 A study of the subacute toxicity of a lyophilised extract of bitter melon at 200 mg/kg/day for 2 months found no statistically significant changes in mean white blood cell or red blood cells counts, haemoglobin, hematocrit, mean cell volume, or mean cell hemoglobin values as compared with controls.7 However, the lack of detailed information about the effects of bitter melon on fertility, fetal development, and pregnancy militate against its use durtng pregnancy until more is known about it. recommended during pregnancy or for those planning a family.

Moreover, bitter melon may have an additive effect when consumed concomitantly with other hypoglycemic agents. In rats, bitter melon juice was found to potentiate the glucose-lowering effects of the sulfonylurea drug tolbutamide.14

Dosages

The dried powders and extracts used in the experimental studies of bitter melon have not been chemically defined, and there is debate about which type of extract is most effective, with some studies suggest that a water based extract is most effective8, 12, 15 while others suggest that alcoholic extracts are more effective6, 9 and still others favoring the dried powdered fruit of the plant.9, 10 These findings illustrate the complexity of producing effective herbal extracts of M. charantia, but indicate that a water-and-ethanol extract may yield the best spectrum of activity. Standardised extracts of M. charantia are typically standardised to 3 to 7% of bitter compounds and to 0.5 to 1% charantin.

Conclusions

Bitter melon is more effective in easing moderate than severe hyperglycemia. It may be more effective in reducing increased serum glucose levels when used in conjunction with a low cholesterol diet. The effects of bitter melon differ from those of insulin in four ways: it has an antihyperglycaemic effect with oral administration, it has a delayed onset of action, it increases the peripheral utilization of glucose even in insulin-independent tissues, and it has a longer duration of activity. Like insulin, bitter melon has an antihyperglycaemic activity. It increases skeletal and hepatic glycogen content and the activity of enzymes involved on glycogenesis. It may help control hyperglycemia, insulin resistance, and hyperlipidemia in Type 2 diabetes and metabolic syndrome. Further clinical study is needed to ascertain the clinical efficacy of M. charantia.

References

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