NATURAL PRODUCT RESEARCH AND DEVELOPMENT ›› 2023, Vol. 35 ›› Issue (7): 1235-1246. doi: 10.16333/j.1001-6880.2023.7.015

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Mechanism of Phellodendri Chinensis Cortex in the treatment of gout based on network pharmacology,molecular docking and experimental validation

LI Min1,2,LI Li2,QUAN Yun-yun2,ZENG Jin2,ZHAO Jun-ning1,2,MAO Jiu-zhou2,GONG Xiao-li2,YIN Zhu-jun2,3*   

  1. 1School of Pharmacy, Chengdu University of Traditional Chinese Medicine,Chengdu 610075,China;2Sichuan Institute for Translational Chinese Medicine,Sichuan Academy of Chinese Medicine Sciences,Chengdu 610041,China;3Hunan Provincial Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations,Changsha Medical University, Changsha 410219,China
  • Online:2023-07-31 Published:2023-07-31

Abstract:

To investigate the potential pharmacodynamic material basis and mechanism of Phellodendri Chinensis Cortex (PCC) in the treatment of gout by combining network pharmacology prediction,molecular docking validation and experimental validation.The active ingredients and action targets of PCC were obtained through TCMSP databases,gout-related disease targets were obtained from GeneCards,OMIM and TTD databases.The corresponding targets of the active ingredients of PCC were intersected with the gout targets,and the protein-protein interaction (PPI) network of the intersected genes was mapped with the help of STRING platform and Cytoscape 3.9.0 software.The analysis of gene ontology (GO) function and Kyoto gene and gene targets (KEGG) pathway enrichment were performed by using String and MetaScape databases and visually presented through the platform of bioinformatics.Furthermore,molecular docking technology was performed to validate the binding pattern and affinity between the key ingredients and the crucial targets by using AutoDock Tools software.A total of 25 active ingredients and 70 potential key targets for the treatment of gout was screened in PCC. The enrichment of GO function and KEGG pathway showed that PCC might positively regulate cell migration,negatively regulate cell differentiation,inflammatory response,positively regulate cell adhesion,protein phosphorylation,DNA transcription and other biological processes.The most crucial biotargets of PCC against gout were protein kinase B1 (AKT1),tumor necrosis factor (TNF),peroxisome proliferative activated receptor gamma (PPAR γ),interleukin-6 (IL-6),prostaglandin-endoperoxide synthase 2(PTGS2),and KEGG enrichment analysis revealed that PCC possessed anti-gout activity by regulating PI3K-Akt signaling pathway,MAPK signaling pathway.The molecular docking results showed that the binding energy between the key biotargets and the five potential active components were much less than -5 kcal/mol.In vitro experiments showed that the core chemical components exhibited potent inhibitory effect on the inflammatory response induced by sodium urate crystal.This study initially revealed PCC has a variety of potential anti-gout active components,and its mechanism may be achieved by modulating multiple biotargets and multiple signal transduction pathways.

Key words: Phellodendri Chinensis Cortex, gout, network pharmacology, molecular docking, experimental validation, anti-inflammatory

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