Elucidating the Therapeutic Potential of Potentilla nivea L. for Rheumatoid Arthritis Through Network Pharmacology, Molecular Docking, and Experimental Validation.

This study explored the molecular mechanism of Potentilla nivea in treating rheumatoid arthritis (RA) using network pharmacology (NP) and experimental validation. In a collagen-induced arthritis (CIA) rat model, treatment with ethanol extract of P. nivea (PN) significantly attenuated joint swelling, reduced arthritis scores, and decreased serum levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). NP predictions identified 107 RA-associated targets across 18 bioactive PN components, with TNF and IL-6 emerging as hub targets through protein-protein interaction (PPI) analysis. Functional enrichment analysis revealed that these targets were associated with apoptosis, oxidative stress, and inflammatory pathways, which were further experimentally validated in RAW264.7 cells. Specifically, PN mitigated hydrogen peroxide-induced apoptosis, ROS production, and LDH release while inhibiting the cleaved-caspase-3, cleaved-PARP, BAX, and BAD proteins. In addition, PN increased levels of p-AMPK, SIRT1, and SIRT3. These findings suggest that P. nivea has a strong therapeutic effect against RA, likely due to its regulation of levels of TNF-α, IL-6, IL-1β, and the AMPK pathway mediated by SIRT. This work provided valuable insights and evidence for understanding the molecular mechanism of P. nivea on RA.