A combination of Psidium guajava leaf and Inula japonica flower extracts attenuates monosodium iodoacetate-induced osteoarthritis in rats

Ethnopharmacological relevance Osteoarthritis (OA) is a progressive degenerative joint disease characterized by chronic inflammation, leading to poor patient quality of life. OA pathogenesis involves the entire joint microenvironment, with proinflammatory cytokines playing vital roles. Traditional herbs that exhibit anti-osteoarthritic effects need to be studied. Aim of the study This study investigated the potential of PGI-cx24 (combination of aqueous Psidium guajava leaf extract and 30% ethanolic Inula japonica flower extract) in alleviating OA using interleukin (IL)-1β/IL-6-stimulated SW1353 human chondrosarcoma-derived cell line and monosodium iodoacetate (MIA)-induced rat model. Materials and methods PGI-cx24 was administered orally once daily for 24 days, starting 3 days before intra-articular MIA injection. Pain-related behavioral assessments; histopathological analysis; and quantification of systemic and local inflammatory mediators, bone turnover markers, matrix metalloproteinases (MMPs), and extracellular matrix (ECM) components were used to evaluate therapeutic efficacy. Complementary in vitro experiments assessed inflammatory and matrix-related gene expression and explored Akt/ERK phosphorylation in cytokine-stimulated SW1353 cells, a human chondrosarcoma-derived cell line. Results In MIA-induced rats, PGI-cx24 significantly attenuated weight-bearing asymmetry and mitigated cartilage degradation and synovial inflammation. PGI-cx24 downregulated proinflammatory cytokines and mediators (IL-1β, tumor necrosis factor, IL-6, cyclooxygenase-2, inducible nitric oxide synthase, 5-lipoxygenase, and leukotriene B4) in serum and joint tissues. PGI-cx24 shifted bone turnover balance by suppressing bone resorption markers (deoxypyridinoline and pyridinoline) while enhancing bone formation marker (procollagen type I N-terminal propeptide). PGI-cx24 protected cartilage integrity by downregulating catabolic MMPs (MMP-2 and MMP-9) while upregulating anabolic ECM components (collagen type II and aggrecan). In vitro results demonstrated that PGI-cx24 effectively suppressed inflammatory and catabolic responses in stimulated chondrocytes. Conclusion PGI-cx24 exerts robust anti-osteoarthritic effects by harmonizing potent anti-inflammatory activity via cartilage matrix homeostasis preservation and bone turnover normalization.