ABSTRACT
Bavachinin (BVC) is a natural small molecule from the Chinese herb Fructus Psoraleae. It exhibits numerous pharmacological effects, including anti-cancer, anti-inflammation, anti-oxidation, anti-bacterial, anti-viral, and immunomodulatory properties. BVC may serve as a novel drug candidate for the treatment of rheumatoid arthritis (RA). Nevertheless, the effects and mechanisms of BVC against RA are still unknown. BVC targets were selected by Swiss Target Prediction and the PharmMapper database. RA-related targets were collected from the GeneCards, OMIM, DrugBank, TTD, and DisGeNET databases. PPI network construction and enrichment analysis were conducted by taking the intersection target of BVC targets and RA-related targets. Hub targets were further screened using Cytoscape and molecular docking. MH7A cell lines and collagen-induced arthritis (CIA) mice were used to confirm the preventive effect of BVC on RA and its potential mechanism. Fifty-six RA-related targets of BVC were identified through databases. These genes were primarily enriched in PI3K/AKT signaling pathway according to KEGG enrichment analysis. Molecular docking analysis suggested that BVC had the highest binding energy with PPARG. The qPCR and western blotting results showed that BVC promoted the expression of PPARG at both the mRNA level and protein level. Western blotting indicated that BVC might affect MH7A cell functions through the PI3K/AKT pathway. Furthermore, treatment with BVC inhibited the proliferation, migration, and production of inflammatory cytokines in MH7A cells and induced cell apoptosis to a certain extent. In vivo, BVC alleviated joint injury and inflammatory response in CIA mice. This study revealed that BVC may inhibit the proliferation, migration, and production of inflammatory cytokines in MH7A cells, as well as cell apoptosis through the PPARG/PI3K/AKT signaling pathway. These findings provide a theoretical foundation for RA therapy.
