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目的探讨栗色鼠尾草Salvia castanea抑制蛋白酪氨酸磷酸酶1B(protein tyrosine phosphatase 1B,PTP1B)的活性成分及其可能的作用机制。方法采用分子克隆技术构建人源PTP1B的体外抑制活性筛选模型,利用该模型对HPLC分离的栗色鼠尾草提取物进行活性成分的追踪分析并进行结构确认,采用分子模拟方法分析其作用机制。结果从栗色鼠尾草根的甲醇提取物中鉴定获得了2个活性化合物,分别为已知化合物二氢丹参酮Ⅰ与丹参酮Ⅱ_A,其IC_(50)分别为34.01μmol/L和44.16μmol/L。分子模拟对接分析揭示了两个化合物的立体构型及作为氢键受体的邻醌结构均有利于与PTP1B的活性位点口袋产生亲和作用。结论丹参酮类化合物对PTP1B具有竞争性抑制作用,并可能成为开发2型糖尿病治疗药物的新资源。
Objective To investigate the inhibitory effect of Salvia castanea on protein tyrosine phosphatase 1B (PTP1B) and its possible mechanism. Methods A molecular cloning technique was used to construct a screening model of human PTP1B in vitro. The model was used to trace and analyze the active constituents of the maroon sage extract separated by HPLC, and its molecular mechanism was analyzed by molecular simulation. Results Two active compounds were identified from the methanol extract of S. sorreliana, and their IC 50 values were 34.01 μmol / L and 44.16 μmol / L, respectively, for the known compounds dihydrotanshinone Ⅰ and tanshinone Ⅱ_A. Mimic docking analyzes revealed that both the stereoconfiguration of the two compounds and the ortho-quinone structure as a hydrogen bond acceptor favored affinity binding to the active site pocket of PTP1B. Conclusion Tanshinones have a competitive inhibitory effect on PTP1B and may be a new resource for the development of type 2 diabetes mellitus.