Mechanisms of polydatin against spinal cord ischemia-reperfusion injury based on network pharmacology, molecular docking and molecular dynamics simulation

Zhicheng Sun; Yuanqing Wang; Xiaoyang Pang; Xiyang Wang; Hao Zeng

doi:10.1016/j.bioorg.2023.106840

Mechanisms of polydatin against spinal cord ischemia-reperfusion injury based on network pharmacology, molecular docking and molecular dynamics simulation

Bioorg Chem. 2023 Nov:140:106840. doi: 10.1016/j.bioorg.2023.106840. Epub 2023 Sep 8.

Authors

Zhicheng Sun¹, Yuanqing Wang², Xiaoyang Pang³, Xiyang Wang⁴, Hao Zeng⁵

Affiliations

¹ Department of Spinal Surgery, Xiangya Hospital of Central South University, Changsha, PR China. Electronic address: 965822816@qq.com.
² School of Life Science and Technology, Central South University of Forestry and Technology, Changsha, PR China. Electronic address: wangyuanqing201@126.com.
³ Department of Spinal Surgery, Xiangya Hospital of Central South University, Changsha, PR China. Electronic address: xiaoyangpang@163.com.
⁴ Department of Spinal Surgery, Xiangya Hospital of Central South University, Changsha, PR China. Electronic address: szc965822816@163.com.
⁵ Department of Spine and Osteopathy Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, PR China. Electronic address: 2621132371@qq.com.

PMID: 37683540
DOI: 10.1016/j.bioorg.2023.106840

Abstract

Background: Polydatin has shown considerable pharmacological activities in ischemia-reperfusion injuries of various organs. However, its effects and mechanisms in spinal cord ischemia-reperfusion injury have not been fully established. In this study, the mechanisms of polydatin against spinal cord ischemia-reperfusion injury were investigated via network pharmacology, molecular docking and molecular dynamics simulation.

Methods: Spinal cord ischemia-reperfusion injury-related targets were obtained from the GeneCards database, while polydatin-related action targets were obtained from the CTD and SwissTarget databases. A protein-protein interaction network of potential targets was constructed using the String platform. After selecting the potential key targets, GO functional enrichment and KEGG pathway enrichment analyses were performed via the Metascape database, and a network map of "drug-target-pathway-disease" constructed. The relationships between polydatin and various key targets were assessed via molecular docking. Molecular dynamics simulation was conducted for optimal core protein-compound complexes obtained by molecular docking.

Results: Topological analysis of the PPI network revealed 14 core targets. GO functional enrichment analysis revealed that 435 biological processes, 12 cell components and 29 molecular functions were enriched while KEGG pathway enrichment analysis revealed 91 enriched signaling pathways. Molecular docking showed that polydatin had the highest binding affinity for MAPK3, suggesting that MAPK3 is a key target of polydatin against spinal cord ischemia-reperfusion injury. Molecular dynamics simulations revealed good binding abilities between polydatin and MAPK3.

Conclusions: Polydatin exerts its effects on spinal cord ischemia-reperfusion injury through multiple targets and pathways. MAPK3 may be a key target of polydatin in spinal cord ischemia-reperfusion injury.

Keywords: Molecular docking; Molecular dynamics simulation; Network pharmacology; Polydatin; Spinal cord ischemia–reperfusion injury.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Molecular Docking Simulation
Molecular Dynamics Simulation*
Network Pharmacology
Reperfusion Injury* / drug therapy
Spinal Cord*

Substances

polydatin