Exploration of the Molecular Mechanism of Polygonati Rhizoma in the Treatment of Osteoporosis Based on Network Pharmacology and Molecular Docking.

Jinlong Zhao,Lingfeng Zeng,Nanjun Xu,Yanhong Han,Minghui Luo,Weiyi Yang,Fangzheng Lin,Jianke Pan,Guihong Liang

doi:10.3389/fendo.2021.815891

Abstract

ObjectiveTo explore the effective components and mechanism of Polygonati Rhizoma (PR) in the treatment of osteoporosis (OP) based on network pharmacology and molecular docking methods.MethodsThe effective components and predicted targets of PR were obtained through the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform (TCMSP) database. The disease database was used to screen the disease targets of OP. The obtained key targets were uploaded to the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database for protein-protein interaction (PPI) network analysis. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of key targets. Analysis and docking verification of chemical effective drug components and key targets were performed with IGEMDOCK software.ResultsA total of 12 chemically active components, 84 drug target proteins and 84 common targets related to drugs and OP were obtained. Key targets such as JUN, TP53, AKT1, ESR1, MAPK14, AR and CASP3 were identified through PPI network analysis. The results of enrichment analysis showed that the potential core drug components regulate the HIF-1 signaling pathway, PI3K-Akt signaling pathway, estrogen signaling pathway and other pathways by intervening in biological processes such as cell proliferation and apoptosis and estrogen response regulation, with an anti-OP pharmacological role. The results of molecular docking showed that the key targets in the regulatory network have high binding activity to related active components.ConclusionsPR may regulate OP by regulating core target genes, such as JUN, TP53, AKT1, ESR1, AR and CASP3, and acting on multiple key pathways, such as the HIF-1 signaling pathway, PI3K-Akt signaling pathway, and estrogen signaling pathway.

Highlights

Osteoporosis (OP) is a systemic metabolic bone disease characterized by bone loss, bone tissue microstructure damage, bone pain and brittle fracture [1]
The active components of Polygonati Rhizoma (PR) were extracted from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) [15, 17]
The compounds were screened according to oral bioavailability (OB) and drug likeness (DL)

Summary

Introduction

Osteoporosis (OP) is a systemic metabolic bone disease characterized by bone loss, bone tissue microstructure damage, bone pain and brittle fracture [1]. The incidence of OP is closely related to age, and with the ageing of the population, OP has become an important factor affecting the quality of life of middle-aged individuals and elderly individuals. Research data show that 40% of postmenopausal women and 30% of men in the world will develop OP [2]. OP may induce other diseases, which causes a heavy economic burden to the patient’s family and society [3]. Most of the drugs for the treatment of OP are chemical drugs that regulate bone metabolism, but there are adverse reactions such as kidney injury and joint pain [4, 5]. Many scholars have studied the efficacy of traditional Chinese medicine in the treatment of OP from the perspective of molecular biology and have made remarkable progress, further proving the positive role of traditional Chinese medicine in the treatment of OP [6, 7]

Methods

Results

Conclusion