Investigation of the Underlying Mechanism of Zhibai Dihuang Pill in Treating Osteoporosis by using Network Pharmacology and Molecular DynamicsSimulation

作者：Baosheng Chang, Yangyang Feng, Liangliang Zhang, Chengjin Zhao, Nannan Li · 发表于：Endocrine Metabolic & Immune Disorders - Drug Targets · 年份：2022 · DOI：10.2174/1871530323666221214144142 · 被引用次数：3 · 研究领域：Phytochemical Studies and Bioactivities、Bone Metabolism and Diseases、Natural product bioactivities and synthesis

BACKGROUND: With society aging, the rising prevalence of osteoporosis (OP) has enormous social and economic implications. At present, the Zhibai Dihuang pill has been clinically applied in OP treatment and shown significant efficacy, but its underlying mechanism remains unclear. AIMS: This study was designed to explore the mechanism of the Zhibai Dihuang pill treating OP. METHODS: In this study, the active ingredients and corresponding targets in the Zhibai Dihuang pill were searched using the TCMSP platform. Based on the mRNA expression data of OP patients in the GEO database, differential expression analysis was conducted by bioinformatics means. By using the differentially expressed genes (DEGs), protein-protein interaction (PPI) network was constructed, and random walk with restart (RWR) analysis based on seed genes intersected from DEGs and drug target genes was conducted. On this basis, the drug-active ingredient-gene interaction network was built. The topological property of the network (degree) was statistically analyzed to find the key therapeutic target AKT1 for the treatment of OP. Molecular docking between AKT1 and the active ingredients was conducted, and according to the affinity score, diosgenin was determined as the key small molecule of the Zhibai Dihuang pill in OP treatment. Based on molecular dynamics simulation and cellular thermal shift assay validation, it was found that diosgenin had a good binding ability with AKT1. RESULTS: Cell experiments showed th...