Network Pharmacology Integrated with Molecular Docking Explores the Mechanisms of Naringin against Osteoporotic Fracture by Regulating Oxidative Stress.

Xiang Yu,Xiaobing Jiang,Lucian Hritcu,Kai Tang,Yanchi Gan,Honglin Chen,Hui Ren,Wenhua Zhao,Bengen Zhou,Qi Shang,Gengyang Shen,Guangye Zhu,De Liang,Peng Zhang,You Zhang,Riwei Tan,Zhida Zhang

doi:10.1155/2021/6421122

Abstract

Naringin (NG), as the most abundant component of Drynariae Rhizoma (Chinese name: Gusuibu), has been proved to be an antioxidant flavonoid on promoting osteoporotic fracture (OF) healing, but relevant research is scanty on the underlying mechanisms. We adopted target prediction, protein-protein interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and molecular docking to establish a system pharmacology database of NG against OF. Totally 105 targets of naringin were obtained, including 26 common targets with OF. A total of 415 entries were obtained through GO Biological Process enrichment analysis (P < 0.05), and 37 entries were obtained through KEGG pathway enrichment analysis with seven signaling pathways included (P < 0.05), which were primarily concerned with p53, IL-17, TNF, estrogen, and PPAR signaling pathways. According to the results of molecular docking, naringin is all bound in the active pockets of the core targets with 3–9 hydrogen bonds through some connections such as hydrophobic interactions, Pi-Pi stacked interactions, and salt bridge, demonstrating that naringin binds tightly to the core targets. In general, naringin may treat OF through multiple targets and multiple pathways via regulating oxidative stress, etc. Notably, it is first reported that NG may regulate osteoclast differentiation and oxidative stress through the expression of the core targets so as to treat OF.

Highlights

Osteoporosis (OP) is a bone disease that often results in severe consequences such as fracture [1, 2]
For better understanding the potential mechanism of NG treatment on Osteoporotic fracture (OF), we adopted an integrative strategy of network pharmacology and molecular docking [13], which would provide a profound theoretical basis for NG application in treating OF
After they were mapped with the target proteins of naringin, ITPS were obtained including 26 intersection targets, which are shown in Figure 1(a) and Table 1

Summary

Introduction

Osteoporosis (OP) is a bone disease that often results in severe consequences such as fracture [1, 2]. Traditional Chinese medicine has been gradually proved to have a functional effect on treating OF, which has attracted increasing attention from more and more scholars [5]. Drynariae Rhizoma (Chinese name: Gusuibu) is widely used to prevent and treat OF and OF-related bone diseases, whose isolated active constituents are composed of flavonoids, phenolic acids, triterpenes, and their glycosides [6]. Flavonoids are the hot spots of current research on the active constituents of Drynariae Rhizoma. Naringin (PubChem CID: 442428), the main ingredient of the flavonoids from Drynariae Rhizoma, has the curative effect of treating osteoporosis and promoting fracture healing, so it has a good application prospect in clinics [6]. For better understanding the potential mechanism of NG treatment on OF, we adopted an integrative strategy of network pharmacology and molecular docking [13], which would provide a profound theoretical basis for NG application in treating OF

Network Pharmacological Data Screening

Network Pharmacological Data Analysis

Results

Discussion

Findings

Conclusion