Exploring the multicomponent synergy mechanism of Zuogui Wan(左归丸) on postmenopausal osteoporosis by a systems pharmacology strategy

作     者：FENG Yanchen LIU Yali DANG Xue LIN Zixuan ZHANG Yunke CHE Zhiying LI Xiang PAN Xiaolong LIU Feixiang ZHENG Pan FENG Yanchen;LIU Yali;DANG Xue;LIN Zixuan;ZHANG Yunke;CHE Zhiying;LI Xiang;PAN Xiaolong;LIU Feixiang;ZHENG Pan

作者机构：Traditional Chinese Medicine (Zhong Jing) SchoolHenan University of Chinese Medicine Hospital of Encephalopathythe First Affiliated Hospital of Henan University of Chinese Medicine State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineResearch Units of Infectious Disease and MicroecologyChinese Academy of Medical Sciences 

出 版 物：《Journal of Traditional Chinese Medicine》 (中医杂志(英文版))

年 卷 期：2024年第44卷第3期

页      面：489-495页

核心收录：

学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 1002[医学-临床医学] 100602[医学-中西医结合临床] 10[医学] 

基　　金：the National Natural Science Foundation of China:Research on Mechanism of Zuogui Wan in Treating Postmenopausal Osteoporosis by Regulating Feed-forward Loop of Oxytocin/Oxytocin Receptor Based on Transcriptome so as to Explain the Theory of “All Marrows Dominated by Brain”(No. 82104730) Based on Protein Kinase Cθ/Nuclear Factor Kappa-B Signal Transduction Regulation,Shexiang Huangqi Compound Dropping Pills Regulate the Migration and Differentiation Mechanism of Mesenchymal Stem Cells Through the Blood-brain Barrier after Cerebral Ischemia (No. 81974564) The 72nd Batch of China Postdoctoral Science Foundation (2022M721065) Central Plains Talent Program-science and Technology Innovation Leading Talent Project (224200510027) 

主　　题：Zuogui Wan network pharmacology osteoporosis, postmenopausal 

摘      要：OBJECTIVE: To explore the multi-component synergistic mechanism of Zuogui Wan(左归丸, ZGW) in treating postmenopausal osteoporosis(PMOP). METHODS: The main components and target genes of ZGW were screened via the Traditional Chinese Medicine Systems Pharmacology(TCMSP). In addition, the target gene sets of PMOP were derived from the Gene Cards and Online Mendelian Inheritance in Man databases. The search tool for recurring instances of neighbouring genes(STRING) 11.0 software was used to analyze the interaction among intersecting genes. Cytoscape 3.6.1 software and the Matthews correlation coefficient(MCC) algorithm were used to screen the core genes. Fifty Sprague-Dawley female rats were randomly divided into the sham-operated(Sham) group and the four ovariectomized(OVX) subgroups. Rats subjected to Sham or OVX were administered with the vehicle(OVX, 1 m L water/100 g weight), 17β-estradiol(E2, 50 μg·kg-1·d-1), and lyophilized powder of ZGW at a low dose of 2.3(ZGW-L) and high dose of 4.6(ZGW-H) g·kg-1·d-1 for three months. The bone density and bone strength were assessed using dual-energy X-ray and three-point bending tests, respectively. Furthermore, enzyme-linked immunosorbent assay, Hematoxylin-eosin staining, and western blot analysis were used to determine the potential pharmacological mechanisms of action of ZGW in PMOP. RESULTS: A total of 117 active compounds of ZGW were screened from the TCMSP. Furthermore, 108 intersecting genes of drugs and diseases were identified. Using STRING software and the MCC algorithm, ten core genes, including C-X-C chemokine living 8(CXCL8), C-C chemokine receptor type 2(CCR2), alpha-2a active receptor(ADRA2A), melatonin receptor type 1B(MTNR1B), and amyloid-beta A4 protein(APP), were identified. The anti-osteoporosis regulation network of ZGW was constructed using the Cytoscape software. The animal experiments demonstrated that ZGW groups significantly reduced the serum levels of β-C-terminal telopeptide of type I collagen(β-CTX