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Tropical Journal of Pharmaceutical Research
Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
ISSN: 1596-5996
EISSN: 1596-9827
Vol. 15, No. 3, 2016, pp. 535-545
Bioline Code: pr16072
Full paper language: English
Document type: Research Article
Document available free of charge

Tropical Journal of Pharmaceutical Research, Vol. 15, No. 3, 2016, pp. 535-545

 en Nobiletin Inhibits Expression of Inflammatory Mediators and Regulates JNK/ERK/p38 MAPK and PI3K/Akt Pathways in Human Osteoarthritic Chondrocytes
Liu, Jian-wei; Hao, Chong-wei; Wang, Zhao-hui & Jin, Dan

Abstract

Purpose: To investigate the anti-inflammatory effects of nobiletin on human osteoarthritic chondrocytes and also to explore possible related molecular events.
Methods: Isolated human osteoarthritic chondrocytes were stimulated with IL-1β. The effect of nobiletin (75, 150 or 300 μg) on chondrocyte viability was assessed. Furthermore, the effect on NO production was determined using Griess reagent while the levels of IL-6 and PGE2 were assessed by enzyme linked immunosorbent assay (ELISA). The influence of nobiletin on the expression of COX-2, iNOS and proteins of PI3/Akt, NF-κB and MAPK cascades were also assessed.
Results: Nobiletin (75, 150 and 300 μg) significantly (p < 0.05) improved the viability of chondrocytes, and remarkably reduced the levels of NO, IL-6 and PGE2. The expression levels of COX-2 and iNOS both at mRNA and protein levels were strikingly reduced by nobiletin, in a dose-dependent way. In addition, nobiletin caused marked (p < 0.05) down-regulation of the NF-κB signalling pathway. IL-1β- induced activation of PI3/Akt, and JNK, ERK and p38 MAPK cascades were significantly (p < 0.05) inhibited by nobiletin with 300 μg dose exhibiting maximum effects.
Conclusion: Inflammatory cytokines are critically involved in the pathogenesis of OA. Significant suppression of cytokines and modulation of PI3/Akt and MAPK signalling cascades by nobiletin suggests its potent anti-inflammatory and anti-osteoarthritic effects.

Keywords
Chondrocytes; Inflammation; Mitogen-activated protein kinases; NF-κB; Nobiletin; Osteoarthritis

 
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