Schisandrin A Inhibits the IL-1ß-Induced Inflammation and Cartilage Degradation via Suppression of MAPK and NF-κB Signal Pathways in Rat Chondrocytes.
Front Pharmacol
; 10: 41, 2019.
Article
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| MEDLINE
| ID: mdl-30761007
ABSTRACT
Osteoarthritis (OA) is a common joint disease in the elderly population. Its development has been reported to be associated with cartilage degradation and inflammatory responses. Schisandrin A, a bioactive lignin in Schisandra sphenanthera, has shown its anti-inflammatory potential in various inflammation diseases. However, the effects of Schisandrin A on OA remain to explore. In this study, rat chondrocytes were treated with IL-1ß (10 ng/ml) with or without different concentrations of Schisandrin A for 24 h. Cell viability was evaluated by CCK-8 assay. Production of nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Griess reaction and ELISA. The MAPK/NF-κB-related signaling molecules expression and the protein production of inducible nitric oxide synthase (iNOS), cyclooxygenase (Cox)-2, MMPs (MMP1, MMP3, MMP13), ADAMTS5, Collagen II, aggrecan, and Sox9 were detected by Western blot. Protein expression of Collagen II, aggrecan, and p65 nuclear translocation was evaluated by immunofluorescence. In vivo, intra-articular injection of 50 µM Schisandrin A or equal volume of vehicle was performed on rat OA models. Severity of cartilage damage was evaluated by HE and Safranin-O-Fast green staining. Our results revealed that Schisandrin A could suppress the IL-1ß-induced production of NO and PGE2 in rat chondrocytes. Consistent with these findings, the upregulation of iNOS and Cox2 could also been decreased by Schisandrin A. Additionally, Schisandrin A could inhibit IL-1ß-induced cartilage matrix catabolic enzymes including MMPs and ADAMTS5. Moreover, the IL-1ß-induced downregulation of Collagen II, aggrecan, and Sox9 could be ameliorated by Schisandrin A. Mechanistically, Schisandrin A functioned by suppressing MAPK and NF-κB signal pathways. In vivo, Schisandrin A prevented cartilage damage in rat OA model. In conclusion, this study elucidates that Schisandrin A inhibits the IL-1ß-induced inflammation and cartilage degradation via suppression of MAPK and NF-κB signal pathways, indicating its potential role in OA therapy.
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MEDLINE
Tipo de estudio:
Prognostic_studies
Idioma:
En
Año:
2019
Tipo del documento:
Article