基于网络药理学的穿心莲抗骨质疏松分子机制研究

Study of molecular mechanism of anti-osteoporosis effect of andrographis paniculata based on network pharmacology

目的基于网络药理学研究方法挖掘穿心莲的活性成分和预测其治疗骨质疏松症的靶点,探究其抗骨质疏松症的分子机制。方法在TCMSP数据库筛选穿心莲的活性化合物,通过PharmMapper反向对接获得药物作用预测靶点。从Gene Crads和CTD数据库搜索疾病靶点,建立药物-疾病靶标交互作用网络,筛选出穿心莲抗骨质疏松的特异性靶点,富集分析其信号通路。结果检索到49种穿心莲的活性化合物,筛选出入血活性成分21种。获得206个药物作用预测靶点和与骨质疏松症发生发展相关的691个疾病靶点,通过药物-疾病靶标交互作用网络筛选出36个关键基因。富集分析结果显示穿心莲直接参与骨质疏松症发生发展的信号通路有Adherens junction、MAPK等。它还间接通过神经营养蛋白、VEGF、Erb B、Toll样受体、胰岛素等信号通路调节骨代谢。结论穿心莲具有治疗骨质疏松症的药物潜能,其作用机制主要通过多靶点和多通路参与骨平衡的调控。

Objective To explore the molecular targets and network regulation mechanism of andrographis paniculata(AP)in the prevention and treatment of osteoporosis(OP)based on network pharmacology.Methods The corresponding active compounds of AP were scanned through TCMSP database.The predicted target of drug action was obtained through PharmMapper reverse docking.The disease targets were searched through GeneCrads and CTD database.A drug-disease target interaction network was established.The specific targets of AP against OP were screened out,and the signal pathway enrichment was analyzed.Results Forty-nine AP corresponding active compounds were found and 21 were found to have blood soluble capacity.Two hundred and six drug predicted targets were obtained.Six hundred and ninety-one target genes associated with OP development were mapped.Thirty-six key genes were screened with establishing drug-disease target interactions.Enrichment analysis revealed that AP was involved in signaling pathways directly in OP,including adherens junction and MAPK signaling pathway.Meanwhile,it also affected bone metabolism by indirect regulation via neurotrophin,VEGF,ErbB,Toll-like receptor,and insulin signaling pathway.Conclusion AP exerts its osteogenic potential via multiple targets and multiple systems,and thus may be a candidate of therapeutic agent for OP.