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

文献类型： 外文期刊

作者： Kong, Xiangyi 1 ; Ning, Can 1 ; Liang, Zengenni 2 ; Yang, Chenglin 1 ; Wu, You 1 ; Li, Yuanyuan 1 ; Wu, Aoao 1 ; Wang, Yongkang 1 ; Wang, Siqi 1 ; Fan, Hui 1 ; Xiao, Wenguang 1 ; Wu, Jing 1 ; Sun, Zhiliang 3 ; Yuan, Zhihang 1 ;

作者机构： 1.Hunan Agr Univ, Coll Vet Med, Hunan Engn Res Ctr Livestock & Poultry Hlth Care, Changsha 410128, Peoples R China

2.Hunan Acad Agr Sci, Dept Hunan Agr Prod Proc Inst, Changsha 410128, Peoples R China

3.Hunan Agr Univ, Coll Vet Med, Hunan Engn Res Ctr Vet Drugs, Changsha 410128, Peoples R China

关键词： Koumine; Osteoarthritis; Extracellular matrix; Mitophagy; PINK1/Parkin

期刊名称：BIOMEDICINE & PHARMACOTHERAPY （ 影响因子：7.5； 五年影响因子：6.8 ）

ISSN： 0753-3322

年卷期： 2024 年 173 卷

页码：

收录情况： SCI

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

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