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作者中文名	作者英文名	单位中文名	单位英文名	E-Mail
王镜勋	WANG Jing-xun	中国医学科学院北京协和医学院药用植物研究所，北京 100193	Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
张方晴	ZHANG Fang-qing	中国医学科学院北京协和医学院药用植物研究所，北京 100193	Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
李如灿	LI Ru-can	中国医学科学院北京协和医学院药用植物研究所，北京 100193	Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
李秋月*	LI Qiu-yue	中国中医科学院望京医院，北京 100102	Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China
石钺*	SHI Yue	中国医学科学院北京协和医学院药用植物研究所，北京 100193	Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China

基金项目:中国中医科学院科技创新工程课题（CI2021A04901）；中国中医科学院望京医院苗圃培育项目（WJYY-YJKT-2022-04）

中文摘要:目的基于网络药理学、分子对接技术探讨补骨脂效应成分抗骨质疏松的作用机制，并进行实验验证。方法采用超高效液相色谱-四极杆-静电场轨道阱飞行时间质谱法表征补骨脂水提取物的化学成分，结合SymMap、Herb、TCM-ID、GEO数据库，STRING平台和Cytoscape软件，筛选了补骨脂抗骨质疏松（OP）的核心药效成分与重要靶点，并进行基因本体（GO）功能富集和京都基因与基因组百科全书（KEGG）通路分析；利用AutoDock软件对核心药效成分与重要靶点进行分子对接验证，通过体外细胞实验进行了初步验证。结果共筛选得到补骨脂效应成分31个、重要靶点256个，其中过氧化物酶体增殖物激活受体γ（PPARG）为核心靶点。GO分析和KEGG信号通路分析分别筛选出符合条件的417个生物过程和123条信号通路，其中有8条核心靶点参与的通路。采用分子对接实验和体外细胞实验对其中腺嘌呤核苷一磷酸激活的蛋白激酶（AMPK）关键信号通路进行验证。分子对接结果显示，补骨脂治疗OP的主要活性成分补骨脂甲素、甲基补骨脂黄酮与蛋白质-蛋白质相互作用网络筛选出的核心靶点蛋白PPARG结合活性较好；细胞实验表明，2个成分可以促进成骨细胞的增殖和分化，对部分AMPK通路相关基因有上调的作用。结论应用网络药理学和生物信息学方法，结合分子对接和细胞实验，可揭示补骨脂有效成分通过AMPK信号通路治疗OP的潜在作用机制，为补骨脂的药效物质基础研究提供了新思路。

中文关键词:补骨脂骨质疏松症网络药理学腺嘌呤核苷一磷酸激活的蛋白激酶作用机制

Exploring Active Components and Mechanism in Treating Osteoporosis of Psoraleae Fructus Based on Network Pharmacology, Molecular Docking, and Experimental Validation

Abstract:Objective To explore the active components and mechanism of Psoraleae Fructus (PF) in treating osteoporosis (OP) based on network pharmacology and molecular docking, and validate the prediction results by experiments.Methods The chemical components of PF aqueous extract were characterized by ultra-performance liquid chromatography-quadrupole/electrostatic field-Orbitrap time-of-flight mass spectrometry. Core active components and important targets of PF in combating OP were retrieved from SymMap, Herb, TCM-ID, GEO, STRING, and Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Molecular docking of core active components with key targets was performed in AutoDock. Furthermore, the prediction results were validated by cell experiments.Results Thirty-one active components and 256 important targets were screened out, among which peroxisome proliferator-activated receptor-gamma (PPARG) was a core target. The GO and KEGG pathway enrichment analyses yielded 417 biological processes and 123 signaling pathways, respectively, with 8 core target-involved pathways. Molecular docking and cell experiments were conducted focusing on the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. The docking results showed that main active components of PF in treating OP, bavachin and bavachinin, had good binding affinity with PPARG identified from the protein-protein interaction (PPI) network. Cell experiments indicated that the two components promoted the proliferation and differentiation of osteoblasts and up-regulated the expression of some genes in the AMPK pathway.Conclusion By employing network pharmacology, bioinformatics methods, molecular docking, and cell experiments, this study reveals the mechanism of the active components of PF in treating OP via the AMPK signaling pathway, giving insights into the pharmacological basis of PF.

keywords:Psoraleae Fructus osteoporosis network pharmacology AMPK mechanism

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