Kaempferol as a multi-targeted phytotherapeutic for arthritis: systematic review and meta-analysis of preclinical...

Arthritis, including rheumatoid arthritis (RA), osteoarthritis (OA), and gouty arthritis (GA), is a major cause of disability worldwide. Current treatments have limited efficacy and adverse effects, prompting interest in natural alternatives. Kaempferol, a flavonoid found in many medicinal plants, has demonstrated anti-inflammatory, antioxidant, and immunomodulatory properties in preclinical arthritis models. To systematically review and quantitatively assess the anti-arthritic effects of kaempferol in in vivo and in vitro models, its impact on inflammatory cytokines, oxidative stress markers, and cartilage degradation enzymes was evaluated. A comprehensive search of PubMed, Web of Science, and Google Scholar up to June 2025 identified relevant studies. Inclusion criteria encompassed in vivo and in vitro models of arthritis treated with pure kaempferol. Outcomes included arthritis score, inflammatory markers (e.g., IL-1β, IL-6, and TNF-α), oxidative stress biomarkers (SOD, MDA, GSH), and MMPs. Quality assessment was performed using SYRCLE's tool and a modified in vitro checklist. Meta-analyses were conducted using RevMan 5.4. Twenty studies (13 in vivo, 7 in vitro) were included. Kaempferol significantly reduced arthritis score (SMD = -2.53), ankle swelling, and histological damage. It downregulated IL-1β (SMD = -6.15), IL-6 (SMD = -14.82), TNF-α (SMD = -13.55), and IL-17, while increasing IL-10. Oxidative stress markers also improved: SOD and GSH increased, MDA decreased. MMP-1 and MMP-9 were significantly suppressed. Subgroup analyses confirmed stronger effects at higher doses and longer durations. Despite high heterogeneity in some outcomes, results consistently favored kaempferol. Kaempferol demonstrates strong anti-arthritic potential via modulation of inflammatory, oxidative, and cartilage degradation pathways in preclinical models. These findings warrant further in vivo validation and eventual clinical trials to determine its therapeutic utility in arthritis management.