Exploring the mechanism of cortex phellodendri chinsis for the treatment of rheumatoid arthritis by regulating ferroptosis based on network pharmacology and molecular docking
10.3760/cma.j.cn141217-20230412-00093
- VernacularTitle:基于网络药理学及分子对接探讨黄柏调控铁死亡治疗类风湿关节炎的作用机制
- Author:
Hui ZHANG
1
;
Yue ZHANG
;
Jiajia BI
Author Information
1. 新乡医学院生命科学技术学院，新乡 453003
- Keywords:
Phellodendri chinensis cortex;
Ferroptosis;
Arthritis, rheumatoid;
Network pharmacology;
Molecular docking simulation
- From:
Chinese Journal of Rheumatology
2024;28(3):176-183
- CountryChina
- Language:Chinese
-
Abstract:
Objective:The potential mechanism of cortex phellodendri chinsis in the improvement of rheumatoid arthritis (RA) through ferroptosis was analyzed based on network pharmacology.Methods:The main active components and their corresponding target proteins were screened by TCMSP database and Herb database, and the UniProt database was used to convert the corresponding target protein names into gene IDs. The targets of RA disease were obtained from GenCards, OMIM, DrugBank and DisGeNET databases. The FerrDb database was used to collect genes for Driver, Suppressors and Markers of ferroptosis. Then, Venny platform was used to obtain the intersection genes of Cortex phellodendri chinsis, RA and ferroptosis, and Cytoscape 3.9.1 software was used to plot the "active component-target-RA-ferroptosis" network diagram. Protein-protein interaction (PPI), gene ontology (GO) function, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using String and DAVID databases. PyMOL, AutoDock Vina software and RCSB PDB database were used for molecular docking between active ingredients and key genes.Results:A total of 11 active components (Quercetin, Beta-sitosterol, Melianone, Candletoxin A, Phellochin, Palmidin A, Worenine, Hispidone, Kihadalactone A, Niloticin, Stigmasterol) and 34 intersection genes (PTGS2、AR、JUN、PRKCA、TGFB1、EGFR、CDKN1A、MAPK1、RB1、IL6、TP53、HIF1A、HSPA5、HMOX1、CAV1、IFNG、ALOX5、PTEN、NFE2L2、PARP1、PPARA、GSTM1、MTOR、PIK3CA、MDM2、MAPK8、GSK3B、SIRT1、DHODH、EZH2、AKR1C2、AKR1C1、STAT3、MAPK3) were screened. Ten possible targets of Cortex phellodendri chinsis regulating ferroptosis and anti-RA were predicted, including TP53、JUN、STAT3、HIF1A、PTEN、SIRT1、EGFR、MTOR、MAPK3、AR. Ferroptosis pathway is regulated by mediating positive regulation of gene expression, response to drugs, HIF-1, FoxO, ErbB and other signaling pathways, thus combating the occurrence and progression of RA. The docking results showed that there were molecular binding sites between the key genes and their corresponding active components.Conclusion:Cortex phellodendri chinsis may treat RA through ferroptosis effect with multiple components, multiple targets, multiple pathways and mechanisms.
