Kaempferia parviflora Extract Stabilizes Cartilage Homeostasis via TIMP-1-Associated Matrix Modulation in Monosodium...

Background: Osteoarthritis (OA) is a degenerative joint disease characterized by extracellular matrix (ECM) breakdown, inflammation, and pain-associated functional impairment. Current pharmacological treatments primarily provide symptomatic relief without preventing cartilage degeneration. Kaempferia parviflora extract (KPE), rich in polymethoxyflavonoids, has been reported to have anti-inflammatory properties; however, its in vivo effects on cartilage homeostasis in OA remain incompletely defined. Methods: A monosodium iodoacetate (MIA)-induced rat model of knee OA was used to evaluate the therapeutic effects of KPE. Following OA induction, rats received oral KPE at low, medium, or high doses for 19 days. Pain-associated functional impairment was assessed by static weight-bearing analysis. Cartilage integrity was evaluated histologically, serum inflammatory and cartilage degradation biomarkers were quantified, and expression of matrix-degrading enzymes and their endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), was analyzed in articular cartilage. Results: MIA injection induced marked joint dysfunction, including an approximately 50% reduction in weight bearing on the affected limb. While KPE did not significantly reduce acute knee swelling, all KPE doses significantly improved weight-bearing imbalance compared with MIA controls. Histological analysis demonstrated preservation of cartilage structure and proteoglycan content in KPE-treated groups. Serum CTX-II levels were significantly reduced across all KPE doses, indicating attenuation of collagen degradation. Systemic inflammatory markers showed differential modulation: significant reductions in serum CRP and COX-2 at medium and high doses, while PGE2 showed a consistent downward trend that did not reach statistical significance. In articular cartilage, KPE treatment restored TIMP-1 expression, whereas modulation of individual MMPs was modest and variable. Conclusions: KPE alleviates OA-associated functional impairment and cartilage degeneration in an experimental OA model. The therapeutic effects are associated with reinforcement of TIMP-1-mediated matrix homeostasis and modulation of inflammatory pathways, supporting the potential of KPE as a natural adjunct candidate for OA management.