Identification of a novel 11β-HSD1 inhibitor from a high-throughput screen of natural product extracts.
作者： Sung Bum Park , Ji Seon Park , Won Hoon Jung , AReum Park , Sae Rom Jo
DOI: 10.1016/J.PHRS.2015.10.014
关键词:
摘要: Selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have considerable potential as a treatment for metabolic syndrome including 2 diabetes mellitus and obesity. To identify 11β-HSD1 inhibitors, we conducted high-throughput screening (HTS) active natural product extracts from the Korea Chemical Bank, Tanshinone I, IIA, flavanone derivatives, 2- 3-phenyl-4H-chromen-4-one. Then IIA its derivatives were targeted development lead compound according to HTS results. However, mechanism anti-adipogenic effect through enzyme inhibition by is not clear. (2a) concentration-dependently inhibited activity in human mouse overexpressed cells 3T3-L1 adipocytes. also activities murine liver fats. Furthermore, (2a)-suppressed adipocyte differentiation cortisone-induced adipogenesis was associated with suppression adipogenesis-specific markers mRNA protein expression. In preadipocytes, (2a)-inhibited cortisone induced reactive oxygen species formation concentration-dependent manner. Thus, these results support therapeutic inhibitor patients.
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