The antihyperglycemic action of myricetin, purified from the aerial part of Abelmoschus moschatus (Malvaceae), was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats). Bolus intravenous injection of myricetin decreased the plasma glucose concentrations in a dose-dependent manner in STZ-diabetic rats. Myricetin at the effective dose (1.0 mg/kg) significantly attenuated the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. A stimulatory effect of myricetin on glucose uptake of the soleus muscles isolated from STZ-diabetic rats was obtained in a concentration-dependent manner from 0.01 to 10.0 micromol/L. The increase of glucose utilization by myricetin was further characterized using the enhancement of glycogen synthesis in isolated hepatocytes of STZ-diabetic rats. These results suggest that myricetin has an ability to enhance glucose utilization to lower plasma glucose in diabetic rats lacking insulin.
In an attempt to develop new substances for treating insulin resistance, obese Zucker rats were employed to screen the effect of myricetin, an active principle of Abelmoschus moschatus (Malvaceae), on insulin resistance. Myricetin purified from the aerial portion of the plant was administered intravenously ( I. V.) into animals. A dose-dependent decrease in the plasma glucose concentration of obese Zucker rats was observed 30 min following an I. V. injection. Moreover, repeated I. V. injection of myricetin (1 mg/kg) into obese Zucker rats 3 times daily for 1 week reduced the value of the glucose-insulin index, an index of insulin resistance calculated from the areas under the curve of glucose and insulin during the intraperitoneal glucose tolerance test. Additionally, repeated myricetin treatments overturned the inability of insulin to increase the expression of glucose transporter subtype 4 (GLUT 4) and to increase the protein levels and phosphorylation of insulin receptor substrate-1 (IRS-1) in soleus muscle of these obese rats. The inability of insulin to increase expression of the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase) and to promote Akt serine phosphorylation in soleus muscle of these rats were also overturned by repeated myricetin treatments. These findings indicate that myricetin improves insulin sensitivity through increased post-receptor insulin signaling mediated by enhancements in IRS-1-associated PI3-kinase and GLUT 4 activity in muscles of obese Zucker rats. Myricetin might be used as a model substance for the development of antidiabetic compounds.
Eight new oxygenated lignans, kadsuphilols A-H (1-8), were isolated from the leaves and stems of Kadsura philippinensis. Four of the isolated lignans (1-4) possess the normal C18-dibenzocyclooctadiene skeleton, while the other four lignans (5-8) are C19-homolignans possessing a substituted cyclohexadienone ring with a spiro-benzofuranoid moiety. The structures of the isolated metabolites were elucidated through spectroscopic analyses, including 2D NMR experiments. Compounds 1 and 4 are the first report of an R-biphenyl configuration with a beta-oxygenated substituent at the C-9 position. The in vitro radical-scavenging activities of these compounds using DPPH were tested and evaluated. Compound 3 exhibited more potent activity than vitamins C and E.
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