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

Abstract：

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 β-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.

journal_name

J Ethnopharmacol

journal_title

Journal of ethnopharmacology

authors

George S,Ajikumaran Nair S,Johnson AJ,Venkataraman R,Baby S

doi

10.1016/j.jep.2015.03.060

subject

Has Abstract

pub_date

2015-06-20 00:00:00

pages

158-63

eissn

0378-8741

issn

1872-7573

pii

S0378-8741(15)00219-6

journal_volume

168

pub_type

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