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- Title
Nobiletin Inhibits Expression of Inflammatory Mediators and Regulates JNK/ERK/p38 MAPK and PI3K/Akt Pathways in Human Osteoarthritic Chondrocytes.
- Authors
Jian-wei Liu; Chong-wei Hao; Zhao-hui Wang; Dan Jin
- 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.
- Subjects
OSTEOARTHRITIS treatment; FLAVONOIDS; PHYSIOLOGICAL effects of cytokines; MITOGEN-activated protein kinases; C-Jun N-terminal kinases; PHOSPHATIDYLINOSITOL 3-kinases; PROTEIN kinase B; EXTRACELLULAR signal-regulated kinases; THERAPEUTICS
- Publication
Tropical Journal of Pharmaceutical Research, 2016, Vol 115, Issue 3, p535
- ISSN
1596-5996
- Publication type
Article
- DOI
10.4314/tjpr.v15i3.15