Antihyperglycemic Effect of Cephalotaxus sinensis Leaves and GLUT-4 Translocation Facilitating Activity of Its Flavonoid Constituents

Abstract

Type 1 diabetes and type 2 diabetes (T2D) rank highly among the top 10 causes of mortality throughout the world. Diabetes patients, particularly those with T2D are at considerable risk of excessive morbidity and mortality from cardiovascular, cerebrovascular, and peripheral vascular diseases leading to myocardial infarction, strokes, and amputations. 1)With the rapid advancements in medicine, novel treatments with fewer side effects have become feasible for the long-term control of this disorder. Recent scientific investigation has confirmed the efficacy of many of plant medicines on diabetes mellitus (DM), some of which are remarkably effective.2) The recommendation of the WHO committee on DM encouraged research on hypoglycemic agents of plant origin used in Chinese traditional medicine and it has greatly motivated research in this area. 3)Insulin-stimulated glucose utilization is the major site for regulation of plasma glucose concentrations.4) Glucose transport is the rate-limiting step in carbohydrate metabolism.5) A family of glucose transporters (GLUT) mediates glucose transport across the cell membrane, and the subtype 4 form (GLUT-4) is the insulin sensitive glucose transporter. Reduction in insulin-mediated glucose uptake caused by decreasing GLUT-4 protein in diabetes, especially T2D, was observed. 6,7) Compounds that facilitate GLUT-4 translocation can be potentially beneficial for the treatment of diabetes, especially for T2D.Cephalotaxus sinensis (REHD et WILE) LI, a medicinal plant and widely distributed in southern China, has been used as a Chinese traditional medicine for treatment of dyspepsia, ascariasis, inflammation, and cough. 8) Alkaloids, flavonoids, biflavonoids, and diterpenes were reported to be constituents of Cephalotaxus species.9-11) It was reported that the ester type alkaloids possessed antitumour activity. 8)Recently, osteoblast differentiation stimulating activity of biflavonoids from Cephalotaxus koreana NAKAI (Cephalotaxaceae) have been reported. 12)To the best of our knowledge, there are no reports on the antihyperglycemic activity of C. sinensis in the literature. As part of a series of experiments to obtain natural products with antidiabetic efficacy from plants, the antihyperglycemic activity of various fractions of the ethanol extract of C. sinensis leaves were evaluated in chronic STZ-induced diabetic rats. The activity of the isolated compounds from the fraction was estimated at the cellular level in vitro. The study elucidated for the first time the biologic properties, namely the activity of facilitating GLUT-4 translocation, of the fraction and its flavonoid constituents from C. sinensis. Furthermore, we characterized the main components of the fraction by using phytochemical and HPLC-DAD methods. HPLC-DAD Conditions An Elite P230 series HPLC-DAD system consisting of a binary pump and a DAD detector (Elite DAD230, P. R. China) was used for acquiring chromatograms and UV spectra. The HPLC condition was as follows: column, Diamonsil TM C 18 column (5 mm, 250ϫ4.6 mm, Di...

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