Fucoxanthin alleviates chondrocyte inflammation and osteoarthritis by modulating the JAK2/STAT3 signaling pathway.

Osteoarthritis (OA) is the most common type of joint degeneration and is a leading cause of chronic disability worldwide. OA is characterized by progressive cartilage degradation, synovial inflammation and oxidative stress within the joint microenvironment. Current pharmacological treatments primarily provide symptomatic relief and are often associated with substantial adverse effects, highlighting the need for new and safe disease‑modifying agents. Fucoxanthin (FUC), a carotenoid pigment found in brown algae, exhibits antioxidant, anti‑inflammatory and chondroprotective properties. Although FUC may have therapeutic effects in OA, the exact mechanisms remain unclear. In the present study, in a post‑traumatic OA rat model induced by anterior cruciate ligament transection, intra‑articular administration of FUC (200 mg/kg) substantially protected the articular cartilage architecture and inhibited proteoglycan loss. In IL‑1β‑stimulated primary rat chondrocytes, FUC markedly decreased the levels of proinflammatory cytokines (IL‑6 at both the mRNA and protein levels and IL‑1β at the protein level) as well as cartilage‑degrading enzymes (MMP3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motifs 5) at the mRNA and protein levels. Furthermore, the chondroprotective and anti‑inflammatory effects of FUC were largely abrogated by RO8191, a selective Janus kinase (JAK)2/STAT3 pathway activator, suggesting that inhibition of the JAK2/STAT3 signaling pathway contributes to FUC‑mediated protective effects. The antioxidant capacity of FUC was evaluated using DPPH and hydroxyl radical scavenging assays, while intracellular reactive oxygen species (ROS) levels in IL‑1β‑stimulated chondrocytes were measured by fluorescence microscopy. FUC demonstrated a dose‑dependent free radical scavenging activity and significantly reduced IL‑1β‑induced intracellular ROS generation in chondrocytes (P<0.05). These findings suggest that FUC may represent a candidate multitarget natural compound for OA that can target oxidative stress, inflammation and extracellular matrix degradation via the JAK2/STAT3 signaling axis. Future investigations should determine the optimal pharmaceutical delivery system, the pharmacokinetics and tissue distribution associated with both local and systemic delivery of FUC, as well as the long‑term safety and efficacy in larger preclinical models and human trials.