Acetyl zingerone inhibits chondrocyte pyroptosis and alleviates osteoarthritis progression by promoting mitophagy through the PINK1/parkin signaling pathway

作者：Zhuangzhuang Zhang, Tianyue Huang, Xu Chen, Jie Chen, Hang Yuan, Yi Ning, Chun‐Bao Miao, Rongbin Sun, Su Ni · 发表于：International Immunopharmacology · 年份：2025 · DOI：10.1016/j.intimp.2025.115055 · 被引用次数：12 · 研究领域：Inflammasome and immune disorders、Spondyloarthritis Studies and Treatments、Gout, Hyperuricemia, Uric Acid

Osteoarthritis (OA) is a common chronic degenerative joint disease, characterized by osteophyte formation and cartilage degeneration. A growing number of studies have found that nod-like receptor pyrin domain 3 (NLRP3) inflammasome-mediated chondrocyte pyroptosis plays a crucial role in the development of OA. Acetyl zingerone (AZ) is a small molecule compound, chemically synthesized to retain the key functional properties of curcumin and zingerone, while exhibiting enhanced anti-inflammatory, antioxidant, and anti-aging effects. Previous studies in our group have found an inhibitory effect on ferroptosis in AZ osteoarthritis. However, its specific mechanism of action has not been fully explained. Therefore, we further delved into whether AZ could alleviate OA in mice by affecting mitophagy and pyroptosis. In an in vitro study, we observed that AZ alleviated LPS + ATP-induced pyroptosis in chondrocytes and inhibited the activation of the NLRP3 inflammasome, a key factor in pyroptosis. Moreover, by using the mitophagy activators Resveratrol, the autophagy lysosome inhibitor chloroquine (CQ) and siPINK1 to knock down PINK1, we demonstrated that AZ promoted PINK1/Parkin-mediated mitophagy. AZ enhanced PINK1/Parkin-mediated mitophagy, facilitating the clearance of damaged mitochondria, thereby reducing reactive oxygen species (ROS) production and suppressing NLRP3 inflammasome activation. This cascade mitigated chondrocyte pyroptosis and promoted collagen synthesis. Moreover, AZ d...