Abstract
Osteoarthritis (OA) is a degenerative joint disease characterized by chronic inflammation and progressive cartilage breakdown. This study investigated the synergistic protective effects of oleaster fruit extract (OE) and Sophora japonica L. fruit extract (SJE) against interleukin-1β (IL-1β) -induced inflammation in human chondrocytes. OE and SJE were tested individually and in combination at various ratios (3:1, 2:1, 1:1, 1:2, and 1:3). Among the tested mixtures, the 3:1 OE:SJE ratio exhibited the most pronounced synergistic effect. When used individually, the concentrations required to achieve 90% cell viability were 313.6 µg/mL for OE and 4135.8 µg/mL for SJE. In contrast, the same viability level was achieved with a combined treatment of 26.4 µg/mL OE and 8.8 µg/mL SJE, yielding a combination index of 0.25, indicative of strong synergy. The 3:1 OE:SJE combination also significantly suppressed inflammatory mediators, including nitric oxide, interleukin-6, and tumor necrosis factor-α. This treatment also led to the downregulation of matrix-degrading enzymes, such as matrix metalloproteinase (MMP)-9 and MMP-13, and it promoted the preservation of hyaluronan, a key extracellular matrix component. These findings suggest that the 3:1 OE:SJE combination exerts a synergistic protective effect by modulating both inflammatory and catabolic pathways and may represent a promising therapeutic strategy for OA prevention or treatment.