Osthole, a potential antidiabetic agent, alleviates hyperglycemia in db/db mice

Hong Jen Liang, Fat Moon Suk, Chung Kwe Wang, Ling Fang Hung, Der Zen Liu, Nai Qi Chen, Yu Chien Chen, Chun Chao Chang, Yu Chih Liang

研究成果: 雜誌貢獻文章

78 引文 斯高帕斯(Scopus)

摘要

Osthole is an agent isolated from Cnidium monnieri (L.) Cusson and Angelica pubescens and has been used to treat several diseases, including metabolic syndromes. To investigate the hypoglycemic effects of osthole in diabetic db/db mice and the underlying mechanisms of these effects by in vitro assay, diabetic db/db mice and cell experiments were utilized to understand its possible effects. Osthole significantly activated both PPARα and PPARγ in a dose-dependent manner based on the results of the transition transfection assay. The activation of PPARα and PPARγ by osthole also resulted in an increase in the expression of PPAR target genes such as PPAR itself, adipose fatty acid-binding protein 2, acyl-CoA synthetases, and carnitine palmitoyltransferase-1A. In vitro results suggested that osthole might be a dual PPARα/γ activator, but its chemical structure differed from that of the thiazolidinedione class of antidiabetic drugs. In addition, osthole markedly activated the AMP-activated protein kinase and its downstream acetyl CoA carboxylase molecules by increasing their phosphorylation levels. Finally, obese diabetic db/db mice were treated with osthole by different administered routes, and osthole was found to markedly reduce blood glucose level. Interestingly, osthole did not reduce the blood insulin or lipid levels, two phenomena that did occur in animals treated with insulin sensitizers like PPAR agonists. These results suggest that osthole can alleviate hyperglycemia and could be potentially developed into a novel drug for treatment of diabetes mellitus.
原文英語
頁(從 - 到)309-315
頁數7
期刊Chemico-Biological Interactions
181
發行號3
DOIs
出版狀態已發佈 - 十月 30 2009

    指紋

ASJC Scopus subject areas

  • Toxicology

引用此