Momordica charantia (bitter melon) reduces plasma apolipoprotein B-100 and increases hepatic insulin receptor substrate and phosphoinositide-3 kinase interactions

Abstract

Aqueous extracts or juice from unripened fruit of Momordica charantia (bitter melon) has traditionally been used in the treatment of diabetes and its complications. Insulin resistance is characterized by significant down-regulation of hepatic insulin signalling as documented by attenuated phosphorylation of insulin receptor (IR), IR substrates 1 and 2, phosphoinositide-3 kinase, protein kinase B, and over-expression of phosphotyrosine phosphatase 1B. We recently demonstrated that bitter melon juice (BMJ) is a potent inhibitor of apoB secretion and TAG synthesis and secretion in human hepatoma cells, HepG2, that may be involved in plasma lipid-and VLDL-lowering effects observed in animal studies. The aim of this study was to evaluate the effects of BMJ on plasma apoB levels and hepatic insulin signalling cascade in mice fed high-fat diet (HFD). Female C57BL/6 mice (4 -6 weeks old) were randomized into three groups receiving regular rodent chow, HFD and HFD þ BMJ. The data indicate that BMJ not only improves glucose and insulin tolerance but also lowers plasma apoB-100 and apoB-48 in HFD-fed mice as well as modulates the phosphorylation status of IR and its downstream signalling molecules. Investigating the biochemical and molecular mechanisms involved in amelioration of diabetic dyslipidaemia by BMJ may lead to identification of new molecular targets for dietary/alternative therapies.Bitter melon: ApoB: Insulin receptor: Phosphorylation: Insulin receptor substrate: Phosphoinositide-3 kinase: Diabetes: Hyperlipidaemia For the past two decades, obesity and associated metabolic disorders such as type 2 diabetes and CVD have been escalating worldwide. Major risk factors for CVD include insulin resistance, hypertension and diabetic dyslipidaemia. Hypertriglyceridaemia and hepatic overproduction of apoB and VLDL are among the most prevalent complications of insulin resistance and are associated with high risk of developing CVD. Currently, diabetes and dyslipidaemia treatments require a combination of drugs. There is no single drug treatment available that will treat both these disorders. Furthermore, available treatments are prone to various side-effects such as secondary weight gain, drug-drug interactions and secondary failure. It is therefore critical to identify new therapies that may influence lipid and glucose metabolism, have minimal side-effects and similar or more potent efficacies than conventional therapies.Momordica charantia, also known as bitter melon (BM), is traditionally used in the treatment of diabetes and its complications (1) . Animal studies also indicate additional effects of BM in regulating weight gain and lipid metabolism (2 -7) .Aqueous extracts of BM fruit and seeds have been demonstrated to reduce VLDL levels in normal control rats, and normalize elevated VLDL levels in diabetic rats (8) . The most fundamental molecular defect in insulin-resistant states is the resistance to cellular actions of insulin, particularly insulin-stimulated glucose uptake, which leads to hyperinsulinaemia, enhan...

Bitter Melon (Momordica charantia) Extract Inhibits Breast Cancer Cell Proliferation by Modulating Cell Cycle Regulatory Genes and Promotes Apoptosis

“…Over the years, there has been a worldwide interest in BME as a dietary supplement because of its various health beneficial effects including lowering diabetes and lipidemia (6,12). A recent study by us reveals that BME is well tolerated, and has been termed as relatively safe in acute, subchronic, and chronic doses in animal studies (6).…”

“…A recent study by us reveals that BME is well tolerated, and has been termed as relatively safe in acute, subchronic, and chronic doses in animal studies (6). Recently, α-eleostearic acid and the dihydroxy derivative from bitter melon were suggested to be the major inducers of apoptosis in HL60 cells (19).…”

“…Freeze-dried bitter melon capsules are available and marketed in health food stores across North America and Western European countries (Eclectic Institute, Inc.). Animal studies have used either fresh bitter melon extract (BME) or crude organic fractions to evaluate its hypoglycemic and hypolipidemic effects (3)(4)(5)(6). Compounds isolated from the fruit and seeds of bitter melon plant that are believed to contribute to its hypoglycemic activity include charantin (a steroid glycoside) and polypeptide "p" or plant insulin (a 166-residue insulin mimetic peptide; refs.…”

Natural remedies for diabetes mellitus

“…Resistance of insulin at cellular level is the most rudimentary defect in NIDDM patients. This resistance of insulin at cellular level causes hypertriacylglycerolaemia, increased VLDL secretion and hyperinsulinemia (Nerurkar et al, 2008). Momordica charantia exert its anti-diabetic effect by improving glucose tolerance and decreasing blood glucose levels.…”

1H NMR-based metabolic study reveals the improvements of bitter melon (Momordica charantia) on energy metabolism in diet-induced obese mouse

“…Correspondingly, recent mechanistic studies have shown that BM or its extracts might activate AMP-associated protein kinase (Tan et al 2008), peroxisome proliferator activating receptors (Chao et al 2011), insulin signals in tissues (Nerurkar et al 2008) and reduce adipose tissue inflammation (Bao et al 2013). Dietary BM supplement leads to the inhibition of adipocyte hypertrophy, down-regulation of lipogenic gene expression in adipose tissue (Huang et al 2008) and increase of lipid oxidation in adipose tissues (Chan et al 2005).…”