Chlorogenic acid ameliorates rabbit osteoarthritis via oxidative stress modulation by targeting the Nrf2/HO-1 pathway

Background Osteoarthritis (OA) is the most common form of arthritis worldwide characterized by progressive degeneration of joint cartilage and underlying bone. Chlorogenic acid (CGA), a dietary polyphenol abundant in plants as coffee, has attracted interest for its potential therapeutic effects. The monosodium iodoacetate-induced rabbit model is widely used because it produces reproducible cartilage destruction, synovial inflammation, and radiographic changes resembling human osteoarthritis, although it represents an accelerated experimental model rather than spontaneous disease. The present study examined whether CGA mitigated OA symptoms induced by MIA in rabbits. Methods Twenty male Baladi rabbits were divided into four groups and followed for six weeks after MIA induction and CGA treatment. The control group received no treatment, the sham group received an intra-articular injection of CGA, the OA group received a single IA injection of MIA, and the OA + CGA group received both MIA and CGA. Oxidative stress was assessed by measuring reduced glutathione (GSH), malondialdehyde (MDA), and biomarkers associated with the Nrf2/HO-1 pathway, while inflammation was evaluated through TNF-α, IL-6, and IL-1β levels. Knee joints were also examined radiographically and histologically. Results CGA significantly improved knee joint pathology, preserving cartilage integrity, reducing synovial hyperplasia and inflammatory infiltration, lowering oxidative stress (↓MDA, ↑GSH), suppressing Nrf2/HO-1 signaling, and decreasing pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α). Conclusion These results highlight the beneficial effects of CGA on MIA-induced OA in rabbits. These findings suggest that CGA exerts a protective effect against OA by attenuating oxidative stress and inflammation and by activating the Nrf2/HO-1 pathway.