Combination therapy of shinbaro and celecoxib improves joint pain and cartilage degradation in an osteoarthritis mouse model

Osteoarthritis is characterized by cartilage degeneration and joint pain, and celecoxib is widely used to treat osteoarthritis, but it has the risk of side effects. We investigated the effect of Shinbaro, a herbal medicine, combined with celecoxib in osteoarthritis. In vitro, primary chondrocytes treated with Shinbaro (200 μg/mL) or celecoxib (0.5 or 1 μM) in the presence of interleukin (IL)-1β (1 ng/mL) for 24 and 48 h were analyzed for cell viability, gene expression, and protein levels. In vivo, mice with osteoarthritis induced via destabilization of the medial meniscus (DMM) surgery were treated with Shinbaro (100 mg/kg) and/or celecoxib (15 or 30 mg/kg) five times weekly for 8 weeks ( n = 7/groups; total n = 42). Cartilage degradation and inflammation were evaluated through behavioral tests, Osteoarthritis Research Society International (OARSI) scoring, and immunofluorescence. The combined treatment did not affect cell viability but reduced the IL-1β-induced expression of extracellular matrix (ECM)-degrading enzymes (matrix metallopeptidase 13 and a disintegrin and metalloproteinase with thrombospondin motifs 5) in chondrocytes. It also inhibited IL-1β-induced mitogen-activated protein kinase pathway activation, showing a synergistic reduction in pro-inflammatory markers compared to single treatments. In a DMM-induced osteoarthritis mouse model, the combined treatment improved weight distribution, reduced mechanical allodynia, and protected against cartilage degradation, evidenced by lower OARSI scores and preserved ECM components (COL2A1, aggrecan). The combined treatment with Shinbaro and celecoxib may offer superior therapeutic benefits in reducing joint pain and degeneration in osteoarthritis by targeting inflammation and preserving cartilage, potentially addressing the limitations of long-term celecoxib use.