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Icariin Alleviates IL-1ß-Induced Matrix Degradation By Activating The Nrf2/ARE Pathway In Human Chondrocytes.
Zuo, Shi; Zou, Wei; Wu, Rong-Min; Yang, Jing; Fan, Jian-Nan; Zhao, Xue-Ke; Li, Hai-Yang.
Afiliación
  • Zuo S; Department of Hepatobiliary Surgery, The Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
  • Zou W; Department of Sports Medicine, The Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
  • Wu RM; Department of Orthopedics, The Fourth People's Hospital of Guiyang, Guizhou, People's Republic of China.
  • Yang J; Department of Ultrasonography, The Maternity Hospital of Guizhou, Guiyang, Guizhou, People's Republic of China.
  • Fan JN; Department of Infectious Disease, The Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
  • Zhao XK; Department of Sports Medicine, The Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
  • Li HY; Department of Infectious Disease, The Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, People's Republic of China.
Drug Des Devel Ther ; 13: 3949-3961, 2019.
Article en En | MEDLINE | ID: mdl-31819369
OBJECTIVE: Osteoarthritis (OA) is characterized by progressive matrix destruction of articular cartilage. This study aimed to investigate the potential antioxidative and chondroprotective effects and underlying mechanism of Icariin (ICA) in interleukin-1 beta (IL-1ß)-induced extracellular matrix (ECM) degradation of OA cartilage. METHODS: Human chondrocyte cell line HC-A was treated with different doses of ICA, and then MTT assay and PI staining were used to estimate ICA-induced chondrocyte apoptosis. Intracellular ROS and superoxide dismutase (SOD) and glutathione peroxidase (GPX) were measured after treatment by IL-1ß with or without ICA. The mRNA and protein expression levels of redox transcription factor Nrf2 and the downstream effector SOD-1, SOD-2, NQO-1 and HO-1 were assayed to explore the detailed mechanism by which ICA alleviates ECM degradation. Finally, to expound the role of Nrf2 in ICA-mediated chondroprotection, we specifically depleted Nrf2 in human chondrocytes and then pretreated them with ICA followed by IL-1ß. RESULTS: ICA had no cytotoxic effects on human chondrocytes and 10-9 M was selected as the optimum concentration. ROS induced by IL-1ß could drastically activate matrix-degrading proteases and ICA could significantly rescue the matrix degradation and excess ROS generation caused by IL-1ß. We observed that ICA activated the Nrf2/ARE pathway, consequently upregulating the generation of GPX and SOD. Ablation of Nrf2 abrogated the chondroprotective and antioxidative effects of ICA in IL-1ß-treated chondrocytes. CONCLUSION: ICA alleviates IL-1ß-induced matrix degradation and eliminates ROS by activating the Nrf2/ARE pathway.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Flavonoides / Medicamentos Herbarios Chinos / Condrocitos / Factor 2 Relacionado con NF-E2 / Interleucina-1beta / Elementos de Respuesta Antioxidante Límite: Humans Idioma: En Revista: Drug Des Devel Ther Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2019 Tipo del documento: Article Pais de publicación: Nueva Zelanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Flavonoides / Medicamentos Herbarios Chinos / Condrocitos / Factor 2 Relacionado con NF-E2 / Interleucina-1beta / Elementos de Respuesta Antioxidante Límite: Humans Idioma: En Revista: Drug Des Devel Ther Asunto de la revista: FARMACOLOGIA / TERAPIA POR MEDICAMENTOS Año: 2019 Tipo del documento: Article Pais de publicación: Nueva Zelanda