女贞子成分抗骨质疏松的潜在作用靶点虚拟筛选

Virtual Screening of Potential Anti-osteoporosis Targets for Compounds From Fructus Ligustri Lucidi

目的:计算筛选女贞子的潜在作用靶点,探索女贞子抗骨质疏松作用靶点的生物学意义。方法:采用Chem Draw、Pharm Mapper软件对抗骨质疏松潜在作用靶点进行虚拟筛选,Cytoscape软件构建生物调控网络模型。结果:女贞子5种成分(特女贞苷、女贞苷Gl3、女贞苷、红景天苷、油女贞苷),能够与骨质疏松相关的多个靶点结合。其中,2个靶点包括GSK-3 beta和CK2-alpha与wnt途径相关,6个靶点(CDPK2、APAF-1、CK2-alpha、DAP kinase 1、CASP-3、ITPK1)与凋亡途径相关;5种成分中,一些成分能与多个抗骨质疏松活性相关的靶点结合,且一些靶点能与多个成分结合。其中,特女贞苷、女贞苷、女贞苷Gl3共同的靶点是APAF-1,特女贞苷、女贞苷、油女贞苷共同的靶点是CK2-alpha。结论:通过女贞子成分靶点筛选,为女贞子成分通过wnt途径、凋亡途径促进骨形成,抑制骨吸收,抗骨质疏松作用的多靶点整合调节机制提供线索。

Objective： To perform computational screening of potential target compounds from Fructus Ligustri Lucidi and to explore the biological significance of these targets which has anti-osteoporotic effect. Methods： Chem Draw and Pharm Mapper software were used to screen target components that were active against osteoporosis in the virtual world. Cytoscape software was used to establish a biological regulation network model. Results： Five components of Fructus Ligustri Lucidi（ specnuezhenide,ligustroflavone G13,ligustroflavone,salidroside and oleonuezhenide） were able to bind different target proteins related to osteoporosis. Two targets,Glycogen synthase kinase（ GSK）-3 beta and Casein kinase（ CK） 2-alpha,were related to the Wnt signaling pathway. Six targets（ Cell division protein kinase [CDPK]-2,Apoptotic protease-activating factor [APAF]-1,CK2-alpha,Death-associated protein [DAP] kinase 1,Caspase[CASP]-3 and Inositol-tetrakisphosphate 1-kinase[ITPK1]） were related to apoptosis pathways.Among the 5 binding components,some had multiple targets while some targets could be associated with different components.Specnuezhenide,ligustroflavone and ligustroflavone G13 were able to combine with APAF-1; specnuezhenide,ligustroflavone and oleonuezhenide shared CK2-alpha. Conclusion： Through screening of Fructus Ligustri Lucidi target components,we found that some components promote bone formation and inhibit bone resorption through alteration of Wnt and apoptosis pathways. It is helpful to understand the multiple target mechanisms of Fructus Ligustri Lucidi components and their anti-osteoporosis effects.