O-prenylated flavonoid, an antidiabetes constituent in Melicope lunu-ankenda.

ETHNOPHARMACOLOGICAL RELEVANCE: Melicope lunu-ankenda leaves are used to treat diabetes in folklore medicinal practices in India and Malaysia. Here we report the isolation of an O-prenylated flavonoid (3,5,4'-trihydroxy-8,3'-dimethoxy-7-(3-methylbut-2-enoxy)flavone; OPF) from the leaves of M. lunu-ankenda and its antidiabetes activity against type-2 diabetes mellitus (T2DM). MATERIALS AND METHODS: OPF was isolated from M. lunu-ankenda leaves by extraction and repeated column chromatography and its structure was elucidated by IR, UV-vis, 1D-, 2D-NMR and mass spectral analyses. Blood glucose lowering activity of OPF was tested in normal rats by oral glucose tolerance test and its efficacy was tested in STZ-induced type-2 diabetic rats. SGOT, SGPT, ALP, serum urea, total triglycerides, total cholesterol and reduction in HDLC, protein and serum insulin levels in normal rats and STZ-induced type-2 diabetic rats were measured. Acute toxicity of OPF was tested at 500 mg/kg dose. Mechanism of antidiabetes action of OPF was elucidated by insulin release from RIN 5F cells. RESULTS: OPF isolated from M. lunu-ankenda showed significant blood glucose lowering activity in oral glucose tolerance test on overnight fasted, glucose loaded normal rats and the optimum activity was observed at a dose of 10mg/kg body weight. In neonatal streptozotocin (STZ) induced diabetic rats, the OPF treatment for 20 days significantly ameliorated the derailed blood glucose levels, liver glycogen and serum biological parameters including insulin to normal levels. OPF on acute toxicity evaluation did not show any conspicuous toxic symptoms even at a higher dose of 500 mg/kg body weight in mice. On evaluating the mechanism of antidiabetes action, it was observed that, OPF induced insulin release from cultured RIN 5F cells in vitro from which it was evident that the OPF acts on pancreatic ß-cells for insulin release thereby correcting the derailed blood glucose levels, serum biochemical parameters and ameliorate various diabetic complications in STZ-induced diabetic rats. CONCLUSIONS: This study shows the potent antidiabetes activity of OPF and describes its mechanism of action. OPF is a promising candidate for the development of new generation anti-DM drugs. Isolation of the O-prenylated flavonoid justifies the use of M. lunu-ankenda for diabetic treatments in folklore practices.

Anti-diabetes and hypoglycaemic properties of Hemionitis arifolia (Burm.) Moore in rats.

Hemionitis arifolia, a folklore anti-diabetes fern, was evaluated for its hypoglycaemic and anti-diabetic properties using rats. Glucose lowering effect and anti-diabetes activity were studied using glucose tolerance test in normal rats and alloxan diabetic rats, respectively. When different extracts were tested, the ethanol and, to some extent, the water extracts were found to lower the levels of blood glucose in glucose fed rats. The ethanol extract showed optimum activity at 200 mg/kg. The extract exhibited only marginal hypoglycaemic activity in overnight fasted normal rats and it was devoid of conspicuous toxic symptoms in sub-acute toxicity evaluation in mice. When the alcohol extract was fractionated by sequential solvent extraction, the activity was found in ethyl acetate fraction (50 mg/kg). This fraction containing steroids and coumarins showed anti-diabetes activity in alloxan diabetic rats as judged from serum glucose levels, liver glycogen content and body weight. This fraction is an attractive material for further research vis-à-vis drug development.