Momordica charantia, a member of the Cucurbitaceae family, is known as bitter melon, bitter gourd, balsam pear, karela, and pare. 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. The unripe fruit is white or green in color and has a bitter taste that becomes more pronounced as the fruit ripens. The seeds, fruit, leaves, and root of the plant have been used in traditional medicine for microbial infections, sluggish digestion and intestinal gas, menstrual stimulation, wound healing, inflammation, fever reduction, hypertension, and as a laxative and emetic. Clinical conditions for which M. charantia extracts (primarily from the fruit) are currently being used include diabetes, dyslipidemia, microbial infections, and potentially as a cytotoxic agent for certain types of cancer.
Active Constituents
Although they have not been definitively determined, research indicates the primary constituents responsible for the properties of Momordica are:
- bitter melon-derived triterpenoids
- momordicin, or 3,7,23-trihydroxycucurbitan-5,24-dien-19-al
- cis-9, trans-11, trans-13 isomer of conjugated linolenic acid.
- charantin,
-insulin-like peptide (plant (p)-insulin): is structurally and pharmacologically similar to bovine insulin and is composed of two polypeptide chains held together by disulfide bonds
-cucurbutanoids,
Molecular mechanism and action
Inside the bitter melon juice there are many different compunds as active constituents, all of them involved in reducing obesity, glycemia and dyslipidemia.
1.Momordica charantia (bitter melon) inhibits primary human adipocyte differentiation by modulating adipogenic genes.
Increase in fat mass is a result of not only increase in adipocyte number due to proliferation, but also induction of differentiation that stimulates mitotic clonal expansion and irreversible commitment to differentiation.
During normal adipogenesis, growth arrest after confluency is followed by mitotic expansion and adipogenic signals to induce differentiation and lipid accumulation. Mitotic clonal growth is accomplished by increased expression of CCAAT/enhancer binding protein beta which further stimulates the expression of two transcription factors, C/EBPα and PPARγ in adipogenesis and lipogenesis. Lower concentrations of Bitter Melon Juice (0.5% to 2%) has no effect on growth arrest or cell death, but may possibly promote dedifferentiation of maturing preadipocytes via reduction in PPARγ mRNA gene expression and reduction in lipogensis.
Momordica charantia (bitter melon) inhibits primary human adipocyte differentiation by modulating adipogenic genes, 2010
2.Bitter gourd inhibits the development of obesity-associated fatty liver in mice fed a high-fat diet.
Mice showed less body and tissue weight gain and less hyperglycemia and hyperlipidemia, less serum interleukin-6 , serum C-reactive protein concentration,
lower liver triglyceride and cholesterol concentrations, less activation of the sterol regulatory element binding protein/fatty acid synthase patway, (SREBPs) that is a class of proteins that transcriptionally activate a cascade of enzymes that are required for the endogenous synthesis of cholesterol, FAs, TGs, and phospholipids.
Among the 3 isoforms, SREBP-1c is the central regulator of lipid metabolism in vivo, and SREBP-1c activation contributes to hepatic lipogenesis and NAFLD.
Bitter gourd inhibits the development of obesity-associated fatty liver in mice fed a high-fat diet,2014
3.Activation of AMPK by bitter melon triterpenoids involves CaMKKβ.
Bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo. BMTs do not activate AMPK directly in an allosteric manner as AMP, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications. BMTs increased AMPK activity and incubation with the CaMKKβ inhibitor, completely attenuated this effect suggesting a key role for CaMKKβ in this activation. Incubation with the calcium chelator did not alter this activation suggesting that the BMT-dependent activation was Ca2+-independent. This study suggests that CaMKKβ is a key upstream kinase for BMT-induced activation of AMPK.
Activation of AMPK by bitter melon triterpenoids involves CaMKKβ,2013
4.Bitter melon seed oil-attenuated body fat accumulation in diet-induced obese mice is associated with cAMP-dependent protein kinase activation and cell death in white adipose tissue.
Bitter melon seed oil (BMSO), which is rich in the cis-9, trans-11, trans-13 isomer of conjugated linolenic acid has an antiadiposity effect becouse increases phosphorylation of acetyl-CoA carboxylase, cAMP-activated protein kinase (PKA), and signal transducer and activator of transcription 3 in the white adipose tissue (WAT), suggesting that PKA and leptin signaling might be involved in the BMSO-mediated reduction in lipogenesis and increase in thermogenesis and lipolysis.
Bitter melon seed oil-attenuated body fat accumulation in diet-induced obese mice is associated with cAMP-dependent protein kinase activation and cell death in white adipose tissue,2012
5.Effects of Momordica charantia on insulin resistance and visceral obesity in mice on high-fat diet.
Bitter melon, traditionally used as an anti-diabetic herb, is effective to improve insulin resistance in a mouse model of Type 2 diabetes possibly by decreasing blood glucose and improving lipid metabolism through the regulation of PPARs-mediated pathway.
Effects of Momordica charantia on insulin resistance and visceral obesity in mice on high-fat diet,2008
Due to its hypoglycemic effects, MC extracts may potentiate the effects of insulin and oral hypoglycemic medications. Patients should be advised to closely monitor blood sugar when adding this botanical to a treatment regimen.
Oral ingestion of bitter melon fruit is safe as demonstrated by long-term consumption of the fruit in Asian cultures. Subcutaneous injection of p-insulin extracted from MC appears to be safe; however, intravenous 4injection of MC extracts is significantly more toxic
and not recommended. Because bitter melon seeds contain momorcharin, shown to have antifertility effects in female mice, bitter melon seed consumption is not recommended
in those seeking to become pregnant.
Dosage recommendations depend on the form of bitter melon being consumed. The dose of fresh juice is 50-100 mL but it is extremely bitter and difficult to drink. Although encapsulated dry powder is easier to ingest, the standard dose is 3-15 g daily – a large dose in capsule form. A standardized, encapsulated extract dosage ranges from 100-200 mg three times daily.
Because seed extracts have been shown to induce abortion in mice and the root is a documented uterine stimulant, use is not recommended in pregnant women or those seeking pregnancy. Although the fruit was not found to induce miscarriage, safety in pregnancy has not been established.
Conclusions
Momordica charantia ( bitter melon ) it’s a phytochemical traditionally used as an antidiabetic, reducing hyperglycemia and rising insulino-sensibility.
Many studies even demonstrate its role in obesity by reducing body and tissue weight gain, liver triglyceride and cholesterol concentrations, differentiation of adipocyte, lipid and cholesterol synthesis, increasing fatty acid oxidation and it’s also demonstrate the interaction of the bitter melon with several enzymatic pathways those improve the conditions in obese subjects.
Its effect on cholesterol synthesis and metabolism suggests its possible use as hypolipidemic to replace drugs as:
- statin or fibrates, that give risk of severe muscle damage (myopathy & rhabdomyolysis),
- niacin that may cause hyperglycemia, and may also cause liver damage,
- bile acid sequestrants those may cause gastrointestinal problems, and may also reduce the absorption of other drugs and vitamins from the gut,
and other hypolipidemic drugs as ezetimibe, lopitamide, orlistat.
In conclusion we can say that Momordica charantia it’s a valid approach to diabets and many studies, not older than 8 years, demonstrates its use in obesity and dyslipidemia.
