Molecular mechanism of Panax ginseng C. A. Meyer against renal fibrosis based on network pharmacology and molecular docking analysis

Abstract

Abstract Renal fibrosis (RF) cause a high morbidity and mortality, while the therapeutic drugs are needed. Panax ginseng C.A. Meyer (PG) was used to treat RF for a long history in China. However, the bioactive components and their corresponding mechanisms are still unclear, which limit the further use of PG. In this study, the potential active components of PG and their corresponding mechanisms against RF were investigated. The triterpene components of PG were screened from the Traditional Chinese Medicine Systems Pharmacology database, and the potential targets of these compounds were predicted with Swiss Target Prediction and Super-PRED tools. The targets related to RF were retrieved through the GeneCards and OMIM databases. The overlapping targets of RF and PG were obtained by Venn diagram. Then, a protein-protein interaction network were constructed by the overlapping targets through the STRING platform and Cytoscape software. The Gene Ontology (GO) functional analysis and KEGG enrichment analysis of the overlapping targets were performed with Metascape database. An active component-core targets-pathways-RF network was constructed with Cytoscape 3.6.1 software. Finally, molecular docking analysis was performed between the active components and core targets by Autodock vina or Ledock software. A total of 49 triterpene components of PG were screened, and 433 targets were identified to be closely related to RF. The five core targets of PG against RF were identified as STAT3, MAPK3, MAPK1, HSP90AA1 and AKT1. The GO analysis revealed that the significant biological processes including protein phosphorylation and responding to hormone, peptide and nitrogen compound. The KEGG pathway analysis demonstrated that the signaling pathways of PI3K-AKT, calcium, HIF-1, cAMP, MAPK play a key role in the therapeutic effect of PG on RF. In addition, the five compounds were suggested as the key ingredients of PG against RF, including panaxatriol, ginsenoside Rh4, pseudoginsenoside R11, panaxadioland 20-(R)-protopanaxatriol. Molecular docking analysis revealed that the five active components could bind to the active sites of the core targets. The triterpenes of PG may act on STAT3, MAPK3, MAPK1, HSP90AA1 and AKT1 against RF, which will provide a new insight for illustrating the pharmacological basis and mechanism of PG against RF.