Anti-arthritic and immunomodulatory effects of geniposide: a systematic review and meta-analysis of preclinical studies.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, joint destruction, and systemic immune dysregulation. Geniposide, an iridoid glycoside derived from Gardenia jasminoides, has shown promising anti-inflammatory and immunomodulatory properties in preclinical studies. This meta-analysis aims to systematically evaluate the therapeutic efficacy and mechanistic pathways of Geniposide in experimental animal models of RA. A comprehensive literature search was conducted using Google Scholar, Science Direct, and PubChem up to June 2025. In vivo studies assessing the effects of Geniposide on arthritis-related outcomes in RA-induced rodent models were included. Data were extracted and analyzed using RevMan 5.4. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. The SYRCLE Risk of Bias tool was used for quality assessment to assess publication bias. Fourteen eligible studies were involved in quantitative synthesis. Geniposide significantly reduced arthritis score, paw swelling, and histopathological joint damage. Pro-inflammatory cytokines IL-6, IL-17, TNF-α, and IL-1β were markedly suppressed, while anti-inflammatory cytokines IL-10 and IL-4 were up-regulated. Mechanistically, Geniposide acted through modulation of NF-κB, MAPK, PTEN/PI3K, and Wnt/β-catenin pathways in reported studies. Geniposide exhibits potent anti-arthritic effects in RA animal models by modulating inflammatory cytokines. These findings highlight its therapeutic potential as a candidate for RA treatment; however, further clinical studies are needed to validate its safety and efficacy in humans.