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Icariin Alleviates IL-1β-Induced Matrix Degradation By Activating The Nrf2/ARE Pathway In Human Chondrocytes.
- Source :
-
Drug design, development and therapy [Drug Des Devel Ther] 2019 Nov 21; Vol. 13, pp. 3949-3961. Date of Electronic Publication: 2019 Nov 21 (Print Publication: 2019). - Publication Year :
- 2019
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Abstract
- 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-1β)-induced extracellular matrix (ECM) degradation of OA cartilage.<br />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-1β 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-1β.<br />Results: ICA had no cytotoxic effects on human chondrocytes and 10 <superscript>-9</superscript> M was selected as the optimum concentration. ROS induced by IL-1β could drastically activate matrix-degrading proteases and ICA could significantly rescue the matrix degradation and excess ROS generation caused by IL-1β. 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-1β-treated chondrocytes.<br />Conclusion: ICA alleviates IL-1β-induced matrix degradation and eliminates ROS by activating the Nrf2/ARE pathway.<br />Competing Interests: The authors declare no conflicts of interest in this work.<br /> (© 2019 Zuo et al.)
- Subjects :
- Apoptosis drug effects
Cells, Cultured
Chondrocytes metabolism
Dose-Response Relationship, Drug
Drugs, Chinese Herbal chemistry
Flavonoids chemistry
Humans
Interleukin-1beta metabolism
Molecular Conformation
NF-E2-Related Factor 2 metabolism
Reactive Oxygen Species analysis
Reactive Oxygen Species metabolism
Signal Transduction drug effects
Structure-Activity Relationship
Antioxidant Response Elements drug effects
Chondrocytes drug effects
Drugs, Chinese Herbal pharmacology
Flavonoids pharmacology
Interleukin-1beta antagonists & inhibitors
NF-E2-Related Factor 2 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1177-8881
- Volume :
- 13
- Database :
- MEDLINE
- Journal :
- Drug design, development and therapy
- Publication Type :
- Academic Journal
- Accession number :
- 31819369
- Full Text :
- https://doi.org/10.2147/DDDT.S203094