Objective  To investigate the medication patterns and formulation characteristics of classical traditional Chinese medicine (TCM) prescriptions for rheumatoid arthritis (RA) treatment and to elucidate the mechanisms of their core active compounds using network pharmacology.

Methods   Five classical TCM prescriptions commonly used in RA treatment were selected, which were Mahuang Jiazhu decoction, Guizhi Shaoyao Zhimu decoction, Xuanbi decoction, Duhuo Jisheng decoction, and Bushen Quhan Zhiwang decoction. Active compounds were screened using the TCMSP database to predict potential targets, and RA-related disease target genes were obtained from the GeneCards database. Common targets among the five prescriptions as well as drug-disease intersection targets were dentified by Venn analysis. A protein-protein interaction (PPI) network was constructed using the STRING database, and key regulatory targets were identified based on topological parameters. GO and KEGG pathway enrichment analyses were conducted in R 4.4.2 to elucidate the mechanisms of action.

Results  The five prescriptions contained a total of 37 Chinese herbal medicines, from which 287 active compounds were identified after deduplication, corresponding to 695 potential targets. The top five most frequently occurring active compounds were β-sitosterol, stigmasterol, kaempferol, quercetin, and catechin. A total of 199 common targets were obtained from the five prescriptions, and 4,210 RA-related targets were retrieved, with 140 overlapping drug-disease targets identified. The compounds with the highest degrees were quercetin, luteolin, kaempferol, wogonin, and β-sitosterol, while the core targets included AKT1, TNF, IL6, TP53, and IL1B. GO enrichment analysis indicated that these targets are primarily involved in biological processes such as response to xenobiotic stimulus, response to molecular stimulus, kinase regulator activity, and cellular membrane and vesicle functions. KEGG enrichment analysis revealed that the main pathways involved include the AGE-RAGE signaling pathway, PI3K-Akt signaling pathway, atherosclerosis, and IL-17 signaling pathway.

Conclusion  The active compounds of these five classical prescriptions may exert therapeutic effects on RA through multi-target and multi-pathway synergistic mechanisms. This study provides a theoretical basis for further basic research and clinical application in RA treatment.

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