Koumine inhibits IL-1β-induced chondrocyte inflammation and ameliorates extracellular matrix degradation in osteoarthritic cartilage through activation of PINK1/Parkin-mediated mitochondrial autophagy

• DOI: 10.1016/j.biopha.2024.116273
• Publication Date: 2024-02-26T12:22:20Z
• Authors: Xiangyi Kong; Can Ning; Zengenni Liang; Chenglin Yang; You Wu; Yuanyuan Li; Aoao Wu; Yongkang Wang; Siqi Wang; Hui Fan; Wenguang Xiao; Jing Wu; Zhiliang Sun; Zhihang Yuan
• Keywords: PINK1

Osteoarthritis (OA) is a degenerative joint disease, Increasingly, mitochondrial autophagy has been found to play an important regulatory role in the prevention and treatment of osteoarthritis. Koumine bioactive alkaloid extracted from plant Gelsemium elegans. In previous research, was have potential improving progression OA rats. However, specific mechanism its action not fully explained. Therefore, aim this study investigate whether can alleviate rats by influencing autophagy. vitro study, rat chondrocytes (RCCS-1) were induced with IL-1β (10 ng/mL) induce inflammation, (50 μg/mL) co-treated. vivo model established intra-articular injection 2% papain, administered orally (1 mg/kg, once daily for two weeks). It that effectively reduced cartilage erosion Additionally, it decreased levels inflammatory factors such as IL-1β, IL-6, extracellular matrix (ECM) components MMP13 ADAMTS5 articular tissue, while increasing level Collagen II.Koumine inhibited production reactive oxygen species (ROS) tissue increased number autophagosomes tissue. upregulated expression proteins LC3Ⅱ/Ⅰ, PINK1, Parkin, Drp1. The administration Mdivi-1 μM) reversed enhanced effect on autophagy, well anti-inflammatory anti-ECM degradation effects OA. These findings suggest chondrocyte inflammation improve activating PINK1/Parkin-mediated