Introduction: Currently natural solutions for health problems including herbal medicines, health foods and dietary supplements

are flooding the markets. Herbal ingredients used for nutraceuticals, health supplements and functional foods are increased and getting more popular. Natural sources used for healing purposes and to promote wellness are not addictive or habit forming, but are powerful nutritional agents that support the immune system naturally. If they are studied with their traditional context the potential of formulating new medicines to promote health and serve as excellent healing agents without side effects is marvelous. Since the herbal food supplements are great body balancers that help regulate body functions, can be used to support restoring process of biological functions and offer the nutrients that the body for maintaining general health. People are greatly concerned about the efficacy and side effects of many synthetic drugs, and hence choose herbal medicines for providing a safe and natural alternative treatment for many health problems. Diabetes mellitus (DM), both insulin-dependent DM (IDDM) and non-insulin dependent DM (NIDDM) is a common and serious metabolic disorder throughout the world. Traditional herbal medicine and natural treatments have been used throughout the world for the therapy of diabetes mellitus. Among many alternative therapies several herbal medicines have been known to cure and control diabetes; additionally they have no side effects but side benefits. History showed that medicinal plants have been used in traditional healing around the world for a long time to treat diabetes; this is because such herbal plants have hypoglycemic properties and other beneficial properties, as reported in scientific literature. There are more than 250 such plants can be listed of which most have clearly shown the scientific evidences efficacy in diabetes mellitus. The findings demonstrated the effects of these plants may delay the development of diabetic complications and provide a rich source for antioxidants that are known to prevent / delay different diseased states. The plants provide a potential source of hypoglycemic drugs because many plants and plant derived compounds have been used in the treatment of diabetes. Many plants available in Asian countries have been investigated for their beneficial use in different types of diabetes and reports occur in numerous scientific journals. Hyperglycemia is involved in the etiology of development of diabetic complications. Ayurveda among all other traditional systems of medicine describes and uses a number of plants used as herbal drugs for the treatment of diabetes. Hence, they play an important role as alternative medicine due to less or no side effects but with additional returns and low cost. The active principles present in medicinal plants have been reported to possess pancreatic beta cells re-generating, insulin releasing and fighting the problem of insulin resistance. As the modern researches suggested the hypoglycemic herbs increase insulin secretion, enhance glucose uptake by adipose or muscle tissues and inhibit glucose absorption from intestine and glucose production from liver. Despite considerable evidences in the treatment of diabetes by herbal hypoglycemic agents, they are yet to be commercially formulated as modern dosage forms, even though they have been acclaimed for their therapeutic properties in the traditional systems of medicine. Momordica chrantia or bitter gourd is a recommended food item in Ayurvedic system of medicine as well as Sri Lankan indigenous medicine for diabetes and associated conditions from the ancient time. Now it is a well-known and world renowned herbal remedy proven for diabetes mellitus which is now being studied by scientists for scientific evidences of its traditionally accepted efficacy. Bitter gourd can be used as an ingredient for any form of health food which is prescribed for diabetes and associated conditions for maintaining optimum health levels. Also it is a safe nutritional supplement as well as an effective antioxidant for preventing the diabetes-like conditions by restoring and regulating the biological functions.
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Traditional information: Vernacular English names of M. charantia include bitter gourd, bitter melon, balsam pear, bitter apple, and bitter, African, or wild cucumber. In Sanskrit it is known as Kravellaka which is translated into Sinhala as Karavila and popular term Karela in India. Botanical synonyms of M. charantia are M. indica L., M. elegans Salisb., M. chinensis Sprengel, and M. thollonii Cogn. M. charantia is an important market vegetable in southern and eastern Asia. In tropical America, local varieties originate from Asia and are cultivated on a small scale only. M. charantia is a common cucurbit and is widely spread throughout most of tropical Africa. The local species of bitter gourd are close to extinction because they are being replaced by commercially cultivated plants. However, they are occasionally collected from the environment as a vegetable or medicinal plant. In India and southeast Asia, cultivated M. charantia is divided into two groups: fruits with a diameter less than 5 cm (var. minima Williams & Ng) and fruits larger than 5 cm in diameter (var. maxima Williams & Ng).4 Other wild African species include M. balsamina L., M. foetida Schum., and M. rostrata A. Zimm. Fruits and leaves of most wild Momordica species are consumed as vegetables, and have a similar bitter taste and almost identical medicinal uses. The immature fruits of M. charantia can be prepared in many ways. In addition to frying or cooking (e.g., for curries), the fruits can be dehydrated, pickled, or canned. They are usually blanched or soaked in salt water before cooking to reduce the bitter taste. Fruits, flowers, and young shoots are also used as a flavoring. The young shoots and leaves are sometimes cooked and eaten as leafy vegetables. Medicinal properties and uses are mentioned in authentic Ayurvedic classical texts like Susruta Samhit, Charaka Samhit, Astangahridaya Samhit, Chakradatta, Bvapraksha, Rja Nighanduva, Rjavallabha Nighanduva, Kaiyadva Nighanduva, Vrinda Mdhava, Gadanigraha etc. Ayurvedic properties: Rasa: tikta, katu Guna: laghu, ruksha Viraya: ushna Vipaka: katu Dosakarma: kaphavtasamaka Dosage: 10 15 ml for fresh juice 2 15 grams for dried crude form Reference sources: 1. 2. 3. 4. WHO Monographs of Medicinal Plants Vol. IV (annexed) Ayurveda Pharmacopeia of India Part I Vol. II (annexed) Indian Materia Medica, K.M. Nadkarni, 1976. pp. 923-4 Encyclopedia of Indian Medicinal Plants; Rational Western Therapy, Ayurvedic and Other Usage, Botany, C.P. Khare, 2004. pp. 315-17 5. Classical Uses of Medicinal Plants, P.V. Sharma, 2004. pp. 94-5
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Nutritional and Chemical Profile 100 grams of fruit of bitter gourd contains Water 94.030 g Energy 17.000 kcal Energy 71.000 kj Protein 1.000 g Total lipid (fat) 0.170 g Ash 1.100 g Carbohydrate, by difference 3.700 g Dietary Fiber 2.800 g Calcium (Ca) 19.000 mg Iron (Fe) 0.430 mg Magnesium (Mg) 17.000 mg Phosphorus (P) 31.000 mg Potassium (K) 296.000 mg Sodium (Na) 5.000 mg Zinc (Zn) 0.800 mg Copper (Cu) 0.034 mg Manganese (Mn) 0.089 mg Selenium (Se) 0.200 mcg Vitamin C total ascorbic acid84.000 mg Thiamin 0.040 mg Riboflavin 0.040 mg Niacin 0.400 mg Pantothenic acid 0.212 mg Vitamin B-6 0.043 mg Folate, total 72.000 mcg (Folic acid Folate, food 72.000 mcg / Folate, DFE 72.000 mcg_DFE) Vitamin A, IU471.000 IU (Vitamin A, RAE24.000 mcg_RAE / Retinol ; Carotene, beta190.000 mcg / Carotene, alpha185.000 mcg) Lutein + zeaxanthin170.000 mcg

According to the scientific literature available there are around 228 different medicinal compounds isolated from the stems, leaves, pericap, entire plant, aerial parts of the plant, endosperm, callus tissues, cotyledons and mainly the seeds and unripe fruit in different laboratories in India, Japan, USA, Thailand, Egypt, China, Taiwan, Australia, Nigeria, Pakistan, Brazil, Nepal, Philippines and Peru. These different compounds belong to different chemical types like proteids, triterpenes, lipids, inorganic compounds, phenylpropanoids, carotenoids, steroids, alkaloids, monoterpenes, alkene to C3, carbohydrates, benzanoids, alkanol C5 or more, other unknown structure (e.g. kakara I-B, II-A and IIIB) sterol and sesquiterpene. Of the 228 different compounds, most of these fall under the groups of proteids and triterpenes. The plant has many different chemical components, which help medicinally either alone or when combined. One of the hypoglycemic components is a steroid saponin called momocharin (charantin) with insulin-like chemical effect. This mainly consists the following chemical constituents those are alkaloids, momordicin and charantin, charine, cryptoxanthin, cucurbitins, cucurbitacins, cucurbitanes, cycloartenols, diosgenin, elaeostearic acids, erythrodiol, galacturonic acids, gentisic acid, goyaglycosides, goyasaponins, guanylate cyclase inhibitors, gypsogenin, hydroxytryptamines, karounidiols, lanosterol, lauric acid,
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linoleic acid, linolenic acid, momorcharasides, momorcharins, momordenol, momordicillin, momordicinin, momordicosides, momordin, momordolo, multiflorenol, myristic acid, nerolidol, oleanolic acid, oleic acid, oxalic acid, pentadecans, peptides, petroselinic acid, polypeptides, proteins, ribosome-inactivating proteins, rosmarinic acid, rubixanthin, spinasterol, steroidal glycosides, stigmastadiols, stigmasterol, taraxerol, trehalose, trypsin inhibitors, uracil, vacine, v-insuline, verbascoside, vicine, zeatin, zeatinriboside, zeaxanthin, zeinoxanthin Amino acidsaspartic acid, serine, glutamic acid, thscinne, alanine, gamino butyric acid and pipecolic acid, ascorbigen, bsistosterol-dglucicide, citruline, elasterol, flavochrome, lutein, lycopene, pipecolic acid. The plant contains several biologically active compounds Chiefly momordicin I & momordicin II, cucurbitacin B. Glycosides ( momordin, charantin, charantosides, goyaglycosides) Terpenoid compounds- momordicinin, momordicilin, momordol Cytotoxic ( ribosome inactivating) proteins such as momorcharin & momordin.

Leaves - Two acidic resins and momordicine (bitter substance), vitamin C, carotene (depending on the sample), aminobutyric acid Roots - About 13% ash (major elements: silicon, calcium, phosphorus, strontium, copper, lead, zinc, sodium, and iron) Fruits - About 7% ash (major elements: see root), no free pectic acid but soluble pectins, saponins, 5hydroxytryptamine, alkaloid momordicine, 0.3% total alkaloid, steroidal glucosides Fresh immature fruits - 0.035% charantin isolated in pure state as a neutral non-nitrogenous principle presenting the characters of phytosterolines Seeds - 32%35% of a purgative fixed oil (stearic acid, oleic acid, linoleic, and _-eleostearic acid); albumin; globulin; glutelin; niacin, pantothenic acid, and other B-vitamins; _-carotene; _-amino butyric acid Dry plant - 0.038% alkaloid (unnamed), 8.35 g/g total carotenoid pigments Entire plant - Trace amounts of alkaloids and saponins, no flavonoids, tannins, quinines, steroids, and terpenes, orthophthalic acid Animal Studies: Anti-hyperglycemic and anti-oxidative effect of aqueous extract of fruit pulp in alloxan-induced diabetic rats reported amelioration of pancreatic histopathological changes associated with STZinduced diabetes in neonatal rats by plant extract are observed. Anti-oxidant and anti-hyperglycemic properties for cardiac tissue during diabetes mellitus by plant extract; anti-diabetic effects reported for fruit extract in insulin-resistant db/db mice; maintenance of normal glucose levels and lipid profiles and prevention of oxidative stress in diabetic rats subjected to chronic sucrose load have been demonstrated. Hypoglycemic and anti-hyperglycemic activity of fruits; anti-hyperglycemic, anti-hyperlipidemic and anti-oxidant effect of polyherbal Ayurvedic formulation containing extract of the plant in STZ-induced
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diabetic rats; beneficial effects for wound healing by extract of fruit in non-diabetic as well as STZinduced diabetic rats are reported. Diabetes ameliorative effects as demonstrated by effect on insulin resistance and skeletal muscle GLUT4 protein in fructose-fed rats; hypoglycemic activity of saponin fraction extracted from the plant; beneficial effect of alcoholic extract of whole fruit powder on pancreatic islets of alloxan diabetic albino rats; effect of plant extract on decreasing insulin resistance and visceral obesity in mice on high fat diet; anti-diabetic activities of triterpenoids isolated from fruits mediated through activation of AMPK pathway are studied. Regeneration of b-cells in islets of Langerhans of pancreas of alloxan diabetic rats by acetone extract of fruits; suppression of postprandial hyperglycemia in rats by extract of plant parts; improvement of insulin sensitivity by increasing skeletal muscle insulinstimulated IRS-1 tyrosine phosphorylation in high-fat-fed rats by fruit extract; anti-diabetic and antilipidemic properties of standardized fruit extract; reparative effects of plant part extract on HIT-T15 pancreatic b-cells are proven. The effect of aqueous extract on increasing glucose uptake and adiponectin (a protein hormone exclusively secreted from adipocytes into bloodstream that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism) secretion in 3T3- L1 adipose cells; inhibitory activity of saponin fraction obtained from the plant on increasing blood glucose and serum neutral fat; hypoglycemic and hypotensive effects of whole plant aqueous extract in rats are reported. Anti-diabetic activity reported for major constituents isolated from the plant; insulin secretagogue and insulinomimetic activities of a slow acting protein from fruit pulp; restoration activity of fruit juice on impaired estrous cycle in alloxan-induced diabetic rats; hypoglycemic effects of crude polysaccharides from the plant in mice; significant hypoglycemic activity of a polyherbal formulation containing aqueous extract of the plant in STZ-induced diabetic mice following administration of Dianex are observed. Anti-oxidant properties of seeds in STZ-induced diabetic rats; reducing effect on adiposity, increased serum adiponectin concentration and increased lipid oxidative enzyme activities freeze-dried fruit juice in diet-induced obese rats fed, which can be beneficial for obese persons for obesity is a leading factor for diabetes; preventive effects in alterations in lipid profile and lipogenic enzymes in alloxan diabetic rats with a combination of sodium orthovanadate and fruit extract are shown. Effect on decreasing triglyceride, low density lipoprotein and increasing high density lipoprotein level and oral glucose tolerance activity of methanol extract of fruit in diabetic rats; synergistic effect of fruit extract with both metformin and glibenclamide in patients with non-insulin dependent diabetes mellitus (NIDDM); stimulation of glucose and amino acid uptakes in L6 myotubes by fruit juice are demonstrated. Partial reversal or normalization of various parameters in STZ-induced diabetic rats by plant juice, including reductions in Na+ and K+-dependent absorptions of glucose by the brush border membrane vesicles of the jejunum, normalization of diabetes-induced reduction in the mean cross-sectional myelinated nerve fibers, axonal area, myelin area and maximal fiber area; suppression of a lowering of energy turnover inherent with aging in diabetic rats by malt vinegar of fruit are studied. Suppressive activity of fruits along with exercise on blood glucose levels in type II diabetic mice; inhibitory action on monosaccharide uptake in rat everted gut sacs in vitro by aqueous extract of
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plant; antihyperglycemic effects of extracts of fresh and dried fruits in diabetic rats; reduction of adiposity, lowering of serum insulin and normalization of glucose tolerance in rats fed a high fat diet by freeze-dried juice of fruits are reported. Prevention of experimental diabetic cataract by extract of the plant; hypoglycemic activity of fruit in type II diabetic mice; partial but significant attenuation of renal hypertrophy in STZ diabetic mice by extract of the plant; substantial prevention by plant extract of hyperglycemia and hyperinsulinemia in high fructose diet fed rats; hypotriglyceridemic and hypocholesterolemic effects of fruit extract in STZinduced diabetic rats are shown. Effect of aqueous extract of fruit on reduction in STZ-induced hyperglycemia in mice, as well as STZinduced lipid peroxidation in pancreas of mice, RIN cells and islets, and STZ-induced apoptosis in RIN cells; anti-atherogenic and hypoglycemic activity of freeze-dried fruit powder in rats fed with cholesterol-free and cholesterol-enriched diets; modulation of xenobiotic metabolism and oxidative stress in STZ-diabetic rats fed with fruit extract suggesting that the extract may play a therapeutic role in management of Type I diabetic patients are observed. hypoglycemic action of alcohol extract of fruit pulp in STZ-diabetic rats; hypoglycemic effect of aqueous extract of fruits reported in normoglycemic and cyproheptadine-induced hyperglycemic mice; hypoglycemic effects reported for fruit pulp, seed, and whole plant in normal and diabetic model rats; delayed cataract formation in diabetic Charles Foster rats with fruit extract; isolation of a galactose binding lectin with insulinomimetic activities from seeds; insulin releasing activity of the plant are shown. Extra pancreatic effect in the form of increased glucose uptake by tissues without concomitant increase in tissue respiration and increased glycogen content of liver and muscle observed with oral administration of fruit juice in rats are proven. Clinical Studies: In a clinical trial conducted, the placebo injection in the control group did not produce any appreciable reduction in blood sugar levels at different intervals. The onset of vegetable insulin effect was observed within 1 hour with the peak effect after 4 hours in six juvenile diabetic patients, after 6 hours in two patients with chemical diabetes mellitus, and after 12 hours in one patient with maturity onset of diabetes mellitus. In an evaluation of dietary fiber on post prandial glycaemia, a diet containing 50 grams of fiber from bitter gourd (5 grams dietary fiber in 100 grams) was associated with significantly lower blood glucose values compared to a control diet. In non-diabetic subjects, there was no significant difference in post prandial glucose when given diets containing 25 grams or 50 grams of fiber from bitter gourd. A negative correlation was observed between fiber content and glucose levels. Administration of an aqueous extract of bitter gourd was more effective in lowering blood sugar in diabetic patients than powder of sun dried bitter gourd fruit. Powder of sun dried bitter gourd fruit was administered orally to five diabetic patients in a dose of 5 grams 3 times daily for 3 weeks. An aqueous extract of bitter gourd fruit juice containing 100 g of fruit in 100 mL of extract was given daily as a single dose in the morning to seven diabetics for 7 weeks. Patients receiving dried fruit had approximately a 25% average in post prandial blood sugar (range 11% to 48%), which was statistically insignificant. The fall in blood sugar in patients receiving the aqueous extract averaged 54%, which
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was significantly more than the group receiving dried fruit. A time related gradual hypoglycemic response was observed in the aqueous extract group over the 7 weeks. Blood sugar was restored to within the normal range in most patients in this group. Glycosylated hemoglobin was significantly reduced after treatment. In other study the bitter gourd seeds produced significant reductions in post prandial blood sugar in patients with insulin dependent and non-insulin dependent diabetes. Seeds were administered in an unspecified dose to twenty diabetic patients. Seeds were administered in an unspecified dose to twenty diabetic patients (14 non-insulin dependent and 6 insulin dependent). Drugs were not used within 24 hours of the test. A fasting blood sugar and blood sugar 120 minutes after breakfast were determined. Post prandial glucose ranged from 350 to 380 mg percent without bitter gourd seeds and from 150 to 180 mg percent with seeds. A fasting glucose on the following day showed a return to original values. Headache and an increase in appetite were reported in a few patients taking bitter gourd seeds. Oral administration of 100 mL of juice from unripe bitter gourd fruit resulted in significantly improved glucose tolerance in thirteen of eighteen newly diagnosed adult onset diabetics not on antidiabetic drugs. Patients had an oral glucose tolerance test with 100 mL sterile water orally 30 minutes before the glucose load. On a subsequent day the test was repeated with 100 mL of bitter gourd fruit juice. The mean total area under the pooled glucose tolerance curve was significantly lower with bitter gourd administration. Oral administration of 100g of bitter gourd extract daily for 2 weeks had no significant effect on blood glucose in twenty-five adult-onset diabetics. Antidiabetic drugs were stopped for a week and fasting and 2-hour post prandial blood sugars were determined prior to the start of the open, controlled study. There was no significant difference between fasting blood glucose before and after ingestion of the extract derived from pulverized fresh fruit of bitter gourd. False negative glycosuria appeared to occur with glucose oxidase reagent strips and Benedicts reagent while taking bitter gourd. This false negative reaction may have been due to the bitter gourd extract keeping the indicator dye in the glucose oxidase strips and the alkaline copper salts in a reduced state. In an open-label, crossover clinical trial, the effect of bitter gourd among Type II diabetic patients with suboptimal glycemic control was assessed. Primary efficacy endpoints were mean changes in HbA1c, FBS and SGPT. Of the 27 subjects enrolled, only twenty-three subjects completed the study. Adverse noted were abdominal cramps, soft stools and increased frequency of bowel movements. There was no episode of hypoglycemia. Among the bitter gourd tea users, there was a reduction in HbA1c of 0.63% and FBS 2.96 mg/dL. SGPT levels were elevated but were not statistically significant. In another clinical trial the postprandial blood sugar was significantly reduced after 3 weeks by 54% in five diabetic patients using aqueous extracts of bitter gourd but not in five patients using the dried powdered fruit in whom blood sugar was reduced by 25%. Blood sugar levels continued to gradually diminish to within normal limits over a 7 week period. Glycosylated hemoglobin was significantly reduced in seven patients from a mean of 8.37% to 6.95%. Bitter gourd juice from the unripe fruit was given in 100 mL doses 30 minutes prior to a glucose tolerance test (GTT) to eighteen previously unmedicated patients with newly diagnosed maturityonset diabetes. Thirteen patients (73%) showed significant improvement at 2 and 2.5 hours after the glucose load over a previous GTT when 100 mL of water was consumed instead of the juice. The
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combined data for patients showed the total area under the curve for glucose was significantly less when it was taken than under control conditions. Nine Asian outpatients with non-insulin dependent diabetes mellitus (6 men and 3 women) were administered three separate 50 gram oral glucose tolerance tests: a standard test, a test with 50 mL bitter gourd juice and a test after 8 to 11 weeks of ingesting fried bitter gourd 0.23 kg daily. Plasma glucose concentrations decreased after bitter gourd juice administration as evidenced by a decrease in area under the curve, which was 5.8 mM/L/min versus 7.0 mM/L/min after the standard test at 60 to 90 minutes (p less than 0.001). Glucose AUC also decreased following intake of fried bitter gourd, to 5.6 mM/L/min at 60 to 90 minutes. Glycosylated hemoglobin significantly decreased in patients ingesting bitter gourd (17.9%) and in patients taking bitter gourd juice as compared to the standard test (19.6%). Insulin levels were not increased. A clinical trial that included nine type I diabetics in the treatment group and ten type I and II diabetics in the placebo group found that injections of bitter gourd extract, isolated for its crystallized p-insulin, resulted in a statistically significant decrease in blood sugar. The effect was noted 3060 minutes after subcutaneous injection, a 21.5% drop from baseline glucose, with a peak effect ranging from 4 12 hours with a 28% drop after 12 hours. This study was not blinded or randomized, and the placebo group had lower average fasting blood glucose at baseline than did the treatment group, all of which may weaken the validity of the results. In a small case series study nine type II diabetics had a baseline glucose tolerance test (GTT) before ingesting 50 mL of bitter gourd juice extracted from about 200 g of fresh bitter gourd fruit, followed by another GTT. 8 to 11 weeks later, after daily ingestion of 0.23 gm of fried bitter gourd, they had another GTT. One hour after the intake of the fried fruit, the mean drop in glucose was 6%. One hour after taking the bitter gourd juice, there was a mean drop of 12% in the GTT. The mean glycosylated hemoglobin (HbA1c) also dropped by about 8% from baseline after the 811 weeks of fried bitter gourd. Type II diabetics were also studied in a case series of eighteen patients. Each patient was given 100 mL of bitter gourd fruit juice 30 minutes before a glucose load and a GTT. Results were compared to each patients own previous GTT taken the day before after drinking just water. A statistically significant improvement was seen in thirteen of the eighteen patients. While each patient served as his or her own control, there was no true control or randomization. Another uncontrolled trial studied a case series of twelve type II diabetics over 3 weeks. Each individual was given 1 of 2 preparations: 1) a bitter gourd aqueous extract of 100 g of chopped boiled bitter gourd in 200 mL of water until it was reduced to 100 mL (given once daily); or 2) 5 g of dried fruit powder (given 3 times daily). After the 21 days, those in the powder group had a 25% reduction in mean blood sugar levels. In the aqueous extract group, there was a significant 54% reduction in mean blood sugar levels, and HbA1c dropped from 8.37 to 6.95. These were promising results, although an uncontrolled study in only twelve patients is not compelling. Lastly, more recently and more importantly, a randomized, double-blind, placebo-controlled, trial was done in type II diabetics using dried bitter gourd fruit and seeds, 3 g/day after meals, for 2 months. Reductions in blood sugar after taking bitter gourd can be seen quicklyas soon as 30 minuteswith the greatest reduction occurring at 4 hours and lasting for 12 hours.

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The favor of bitter gourd for the reduction of glycosylated hemoglobin and the ability of bitter gourd to decrease serum glucose levels have been investigated in many animal studies and in a small number of human studies. Research Papers: Abdollahi, M., A.B. Zuki, Y.M. Goh, A. Rezaeizadeh and M.M. Noordin, 2011. Effects of Momordica charantia on pancreatic histopathological changes associated with streptozotocin-induced diabetes in neonatal rats. Histology and Histopathology, 26: 13-21. Ahmed, I., M.S. Lakhani, M. Gillett, A. John and H. Raza, 2001. Hypotriglyceridemic and hypocholesterolemic effects of anti-diabetic Momordica charantia (karela) fruit extract in streptozotocin-induced diabetic rats. Diabetes Research and Clinical practice, 51: 155-161. Ahmed, I., E. Adeghate, E. Cummings, A.K. Sharma and J. Singh, 2004. Beneficial effects and mechanism of action of Momordica charantia juice in the treatment of streptozotocin-induced diabetes mellitus in rat. Molecular and Cellular Biochemistry, 261: 63-70. Ali, L., A.K. Khan, M.I. Mamun, M. Mosihuzzaman, N. Nahar, M. Nur-e-Alam and B. Rokeya, 1993. Studies on hypoglycemic effects of fruit pulp, seed, and whole plant of Momordica charantia on normal and diabetic model rats. Planta Medica, 59: 408-412. Baldwa V, C. Bhandari, A. Pangaria, R. Goyal. 1977. Clinical trial in patients with diabetes mellitus of an insulin-like compound obtained from plant sources. Upsala Journal of Medicine. 82:39-41. Cakici, I., C. Hurmolu, B. Tuntan, N. Abaciolu, I. Kanzik and B. Sener, 1994. Hypoglycaemic effect of Momordica charantia extracts in normoglycaemic or cyproheptadine-induced hyperglycaemic mice. Journal of Ethnopharmacology, 44: 117-121. Chan, L.L., Q. Chen, A.G. Go, E.K. Lam and E.T. Li, 2005. Reduced adiposity in bitter gourd (Momordica charantia)-fed rats is associated with increased lipid oxidative enzyme activities and uncoupling protein expression. Journal of Nutrition, 135: 2517-2523. Chaturvedi, P., S. George, M. Milinganyo and Y.B. Tripathi, 2004. Effect of Momordica charantia on lipid profile and oral glucose tolerance in diabetic rats. Phytotherapy Research, 18: 954-956. Chaturvedi P, S. George, M. Milinganyo, Y. Tripathi, 2004. Effect of Momordica charantia on lipid profile and oral glucose tolerance in diabetic rats. Phytotherapy Research.18:954-56. Chaturvedi, P. and S. George, 2010. Momordica charantia maintains normal glucose levels and lipid profiles and prevents oxidative stress in diabetic rats subjected to chronic sucrose load. Journal of Medicinal Food,13: 520-527. Chen, Q., L.L. Chan and E.T. Li, 2003. Bitter gourd (Momordica charantia) reduces adiposity, lowers serum insulin and normalizes glucose tolerance in rats fed a high fat diet. Journal of Nutrition, 133: 1088-1093. Cummings, E., H.S. Hundal, H. Wackerhage, M. Hope, M. Belle, E. Adeghate and J. Singh, 2004. Momordica charantia fruit juice stimulates glucose and amino acid uptakes in L6 myotubes. Molecular and Cellular Biochemistry, 261: 99-104.

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Dans A, M. Villarruz, C. Jimeno, 2007. The effect of Momordica charantia capsule preparation on glycemic control in type 2 diabetes mellitus needs further studies. Journal of Clinical Epidemiology. 60(6):554-559. Fernandes, N.P., C.V. Lagishetty, V.S. Panda and S.R. Naik, 2007. An experimental evaluation of the antidiabetic and antilipidemic properties of a standardized Momordica charantia fruit extract. BMC Complementary and Alternative Medicine, 7: 29. Han, C., Q. Hui and Y. Wang, 2008. Hypoglycaemic activity of saponin fraction extracted from Momordica charantia in PEG/salt aqueous two-phase systems. Natural Product Research, 22: 11121119. Harinantenaina, L., M. Tanaka, S. Takaoka, M. Oda, O. Mogami, M. Uchida and Y. Asakawa, 2006. Momordica charantia constituents and antidiabetic screening of the isolated major compounds. Chemical & Pharmaceutical Bulletin (Tokyo), 54: 1017-1021. Hongxiang Hui, George Tang, and Vay Liang W Go. VLW. Hypoglycemic herbs and their action mechanisms. Chin Med 2009, 4, 11-14. Ichikawa, M., M. Ohta, S. Kanai, Y. Yoshida, S. Takano, T. Ueoka, T. Takahashi, K. Kimoto, A. Funakoshi, and K. Miyasaka, 2003. Bitter gourd malt vinegar increases daily energy turnover in rats. Journal of Nutritional Science and Vitaminology (Tokyo), 49: 428-433. Jayasooria, A.P., M. Sakono, C. Yukizaki, M. Kawano, K. Yamomoto and N. Fukuda, 2000. Effects of Momordica charantia powder on serum glucose levels and various lipid parameters in rats fed with cholesterol-free and cholesterol-enriched diets. Journal of Ethnopharmacology, 72: 331-336. Leatherdale B, R. Panesar, G. Singh, 1981. Improvement in glucose tolerance due to Momordica charantia (karela). British Medical Journal (Clin Res Ed). 282(6279):1823-1824. Mahomoodally, M.F., A.G. Fakim and A.H. Subratty, 2004. Momordica charantia extracts inhibit uptake of monosaccharide and amino acid across rat everted gut sacs in-vitro. Biological & Pharmaceutical Bulletin, 27: 216-218. Miura, T., C. Itoh, N. Iwamoto, M. Kato, M. Kawai, S.R. Park and I. Suzuki, 2001. Hypoglycemic activity of the fruit of the Momordica charantia in type 2 diabetic mice. Journal of Nutritional Science and Vitaminology (Tokyo), 47: 340-344. Miura, T., Y. Itoh, N. Iwamoto, M. Kato and T. Ishida, 2004. Suppressive activity of the fruit of Momordica charantia with exercise on blood glucose in type 2 diabetic mice. Biological & Pharmaceutical Bulletin, 27: 248-250. Ng, T.B., C.M. Wong, W.W. Li and H.W. Yeung, 1986. Isolation and characterization of a galactose binding lectin with insulinomimetic activities from the seeds of the bitter gourd Momordica charantia (Family Cucurbitaceae). International Journal of Peptide and Protein Research, 28: 163-172. Ojewole, J.A., S.A. Adewole and G. Olayiwola, 2006. Hypoglycaemic and hypotensive effects of Momordica charantia Linn (Cucurbitaceae) whole-plant aqueous extract in rats. Cardiovascular Journal of South Africa, 17: 227-232.

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Raza, H., I. Ahmed, A. John and A.K. Sharma, 2000. Modulation of xenobiotic metabolism and oxidative stress in chronic streptozotocin-induced diabetic rats fed with Momordica charantia fruit extract. Journal of Biochemical and Molecular Toxicology, 14: 131-139. Reyes, B.A., N.D. Bautista, N.C. Tanquilut, R.V. Anunciado, A.B. Leung, G.C. Sanchez, R.L. Magtoto, P. Castronuevo, H. Tsukamura and K.I. Maeda, 2006. Anti-diabetic potentials of Momordica charantia and Andrographis paniculata and their effects on estrous cyclicity of alloxan-induced diabetic rats. Journal of Ethnopharmacology, 105: 196-200. Roffey, B.W., A.S. Atwal, T. Johns and S. Kubow, 2007. Water extracts from Momordica charantia increase glucose uptake and adiponectin secretion in 3T3-L1 adipose cells. Journal of Ethnopharmacology, 112: 77-84. Sarkar, S., M. Pranava and R. Marita, 1996. Demonstration of the hypoglycemic action of Momordica charantia in a validated animal model of diabetes. Pharmacological Research, 33: 1-4. Satishsekar, D. and S. Subramanian, 2005. Antioxidant properties of Momordica charantia (bitter gourd) seeds Sekar, D.S., K. Sivagnanam and S. Subramanian, 2005. Antidiabetic activity of Momordica charantia seeds on streptozotocin induced diabetic rats. Pharmazie, 60: 383-387. Shih, C.C., C.H. Lin and W.L. Lin, 2008. Effects of Momordica charantia on insulin resistance and visceral obesity in mice on high-fat diet. Diabetes Research and Clinical Practice, 81: 134-143. Shih, C.C., C.H. Lin, W.L. Lin and J.B. Wu, 2009. Momordica charantia extract on insulin resistance and the skeletal muscle GLUT4 protein in fructose-fed rats. Journal of Ethnopharmacology, 123: 82-90. Singh, N. and M. Gupta, 2007. Regeneration of b cells in islets of Langerhans of pancreas of alloxan diabetic rats by acetone extract of Momordica charantia (Linn.) (bitter gourd) fruits. Indian Journal of Experimental Biology, 45: 1055-1062. Singh, N., M. Gupta, P. Sirohi and Varsha, 2008. Effects of alcoholic extract of Momordica charantia (Linn.) whole fruit powder on the pancreatic islets of alloxan diabetic albino rats. Journal of Environmental Biology, 29: 101-106. Sitasawad, S.L., Y. Shewade and R. Bhonde, 2000. Role of bittergourd fruit juice in STZ-induced diabetic state in vivo and in vitro. Journal of Ethnopharmacology, 73: 71-79. Sridhar, M.G., R. Vinayagamoorthi, V. Arul Suyambunathan, Z. Bobby and N. Selvaraj, 2008. Bitter gourd (Momordica charantia) improves insulin sensitivity by increasing skeletal muscle insulinstimulated IRS-1 tyrosine phosphorylation in high-fat-fed rats. British Journal of Nutrition, 99: 806-812. Srivastava, Y., H. Venkatakrishna-Bhatt and Y. Verma, 1988. Effect of Momordica charantia Linn. Pomous aqueous extract on cataractogenesis in murrin alloxan diabetics. Pharmacological Research Communications, 20: 201-209. Srivastava Y., 1993. Antidiabetic and adaptogenic properties of Momordica charantia extract: an experimental and clinical evaluation. Phytotherapy Research. 7:285-289. Teoh, S.L., A.A. Latiff and S. Das, 2009. The effect of topical extract of Momordica charantia (bitter gourd) on wound healing in nondiabetic rats and in rats with diabetes induced by streptozotocin. Clinical and Experimental Dermatology, 34: 815-822.
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Tongia, A., S.K. Tongia and M. Dave, 2004. Phytochemical determination and extraction of Momordica charantia fruit and its hypoglycemic potentiation of oral hypoglycemic drugs in diabetes mellitus (NIDDM). Indian Journal of Physiology and Pharmacology, 48: 241-244. Tripathi, U.N. and D. Chandra, 2009. The plant extracts of Momordica charantia and Trigonella foenumgraecum have anti-oxidant and anti-hyperglycemic properties for cardiac tissue during diabetes mellitus. Oxidative Metabolism and Cell Longevity, 2: 290-296. Tripathi, U.N. and D. Chandra, 2010. Anti-hyperglycemic and anti-oxidative effect of aqueous extract of Momordica charantia pulp and Trigonella foenum graecum seed in alloxan-induced diabetic rats. Indian Journal of Biochemistry and Biophysics, 47: 227-233. Uebanso, T., H. Arai, Y. Taketani, M. Fukaya, H. Yamamoto, A. Mizuno, K. Uryu, T. Hada and E. Takeda, 2007. Extracts of Momordica charantia suppress postprandial hyperglycemia in rats. Journal of Nutritional Science and Vitaminology (Tokyo), 53: 482-488. Vikrant, V., J.K. Grover, N. Tandon, S.S. Rathi and N. Gupta, 2001. Treatment with extracts of Momordica charantia and Eugenia jambolana prevents hyperglycemia and hyperinsulinemia in fructose fed rats. Journal of Ethnopharmacology, 76: 139-143. Virdi, J., S. Sivakami, S. Shahani, A.C. Suthar, M.M. Banavalikar and M.K. Biyani, 2003. Antihyperglycemic effects of three extracts from Momordica charantia. Journal of Ethnopharmacology, 88: 107-111. Wadkar KA, Magdum CS, Patil SS, Naikwade NS. Antidiabetic potential and Indian medicinal plants. J Herbal Med and Toxicol 2008, 2, 45-50. Welihinda, J., G. Arvidson, E. Gylfe, B. Hellman and E. Karlsson, 1982. The insulin-releasing activity of the tropical plant Momordica charantia. Acta Biologica et Medica Germanica, 41: 1229-1240. Welihinda, J. and Karunanayake, E.H.,1986. Extra-pancreatic effects of Momordica charantia in rats. Journal of Ethnopharmacology, 17: 247-255. Welihinda J, E.H. Karunanayake, M. Sheriff, 1986. Effect of Momordica charantia on the glucose tolerance in maturity onset diabetes. Journal of Ethnopharmacology. 17(3):277-282. Xiang, L., X. Huang, L. Chen, P. Rao and L. Ke, 2007. The reparative effects of Momordica charantia Linn. extract on HIT-T15 pancreatic b-cells. Asia Pacific Journal of Clinical Nutrition, 16 Suppl 1: 249252. Yibchok-anun, S., S. Adisakwattana, C.Y. Yao, P. Sangvanich, S. Roengsumran and W.H. Hsu, 2006. Slow acting protein extract from fruit pulp of Momordica charantia with insulin secretagogue and insulinomimetic activities. Biological & Pharmaceutical Bulletin, 29: 1126-1131. Zheng, Z.X., J.Y. Teng, J.Y. Liu, J.H. Qiu, H. Ouyang and C. Xue, 2005. The hypoglycemic effects of crude polysaccharides extract from Momordica charantia in mice. Wei Sheng Yan Jiu, 34: 361-363. (Original in Chinese) http://www.ncbi.nlm.nih.gov/pubmed/16111053

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Annexure I WHO Monographs of Medicinal Plants, Vol. IV, World Health Organization, 2007 pp. 192-209

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Annexure II The Ayurvedic Pharmacopoeia of India, Part I, Vol. II, Government of India, pp. 89-90

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Annexure III Indian Medicinal Plants: An Illustrated Dictionary, C.P. Khare (ed.), Spronger, 2010, pp. 418-20

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Annexure IV Pharmacographia Indica: A History of the Principal Drugs of Vegetable Origin met within British India, Vol. II. William Dymock, C.J.H. Warden, David Hooper, Thacker Spink & Co., 1891. pp. 78-9

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Annexure V Handbook of Medicinal Plants, James A. Duke, CRC Press, New York, 1929, pp. 78-9

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