In silico and In vitro Analysis of Coniferin Mediates Apoptosis by Intervening the PTGS2/Apoptosis Pathway to Alleviate Rheumatoid Arthritis

Purpose: Liquidambaris Fructus (LF), a prevalent Chinese medicinal herb, has been effectively utilized in the clinical treatment of rheumatoid arthritis (RA). Coniferin, is the active ingredient in LF, and there is a paucity of research examining its potential anti-RA properties. This study employs in silico analysis and experimental validation to delve into the therapeutic potential of Coniferin against RA and to elucidate its mechanism of action. Methods: In silico analysis was employed to construct a drug-disease target protein-protein interaction (PPI) network, to perform functional enrichment analysis, and to molecular docking of the principal compounds and target proteins. Subsequently, the effects of coniferin on the proliferation, migration, and invasion of rheumatoid arthritis - Fibroblast-like synoviocytes (RA-FLSs) were observed using a CCK8 assay and Transwell assay. ELISA was employed to detect the inflammatory response of RA-FLSs in coniferin. Flow cytometry was utilized to detect the effects of coniferin on apoptosis, oxidative stress, and mitochondrial transmembrane potential in RA-FLSs. Ultimately, the expression of pivotal proteins and apoptosis markers within the PTGS2/Apoptosis signaling pathway was discerned through the utilization of Real-time quantitative PCR (RT-qPCR) and Western blot. Results: It was observed that coniferin promotes apoptosis of RA-FLSs through the PTGS2/Apoptosis signaling pathway and inhibits the proliferation, migration, and invasion of RA-FLSs, with anti-inflammatory, oxidative stress-reducing, and mitochondrial transmembrane potential disruption effects. Conclusion: The potential mechanism of coniferin for the treatment of RA is to promote apoptosis of RAFLSs by intervening in the PTGS2/apoptosis signaling pathway.