Integrating network pharmacology and experimental validation via PPAR signaling to ameliorate rheumatoid arthritis: Insights from Corydalis Decumbentis Rhizoma (Xiatianwu).

Corydalis Decumbentis Rhizoma (Xiatianwu, XTW) exhibits a positive effect in treating rheumatoid arthritis (RA). However, the precise molecular mechanisms underlying its effects remain unclear. In this study, TNF-α was used to induce inflammation and establish and in vitro RA model. Network pharmacology was employed to identify the important active components and targets in the treatment of XTW on RA. CCK-8 was used to investigate the cell viability. GW9662 (a PPARG antagonist) was applied to validate the network pharmacology prediction. ELISA was used to measure pro-inflammatory cytokines (IL-6, IL-1β, and INF-γ) and oxidative stress markers (MMP-2, MDA, and ROS). HPLC-MS was conducted to validate the four important active ingredients (bicuculline, ferulic acid, berberine, and jatrorrhizine) in XTW. Western blotting was carried out to detect the protein levels of PPAR-γ. In vitro experiments demonstrated that XTW exerted dose-dependent anti-RA effects by downregulating pro-inflammatory cytokines and oxidative stress markers. Through Network pharmacology, three targets (RXRA, PPARG, and PPARA) and four active ingredients (bicuculline, ferulic acid, berberine, and jatrorrhizine) were demonstrated important in the treatment of XTW on RA. Besides, PPAR signaling pathway may be a therapeutic target for XTW treating RA. Further experiments confirmed that XTW administration significantly inhibited inflammation and oxidative stress by upregulating the PPAR signaling pathway. In conclusion, XTW modulates RXRA, PPARG, and PPARA through the PPAR signaling pathway, thereby mitigating inflammation and oxidative stress in RA.