Sinapic Acid Inhibits the IL-1β-Induced Inflammation via MAPK Downregulation in Rat Chondrocytes
Osteoarthritis (OA) is a degenerative joint disease frequently seen in the elderly population. Sinapic acid (SA), a commonly found phenolic acid, has been pharmacologically evaluated for its anti-inflammation effects in various studies. To explore its potential therapeutic role for OA, rat chondrocytes were treated with IL-1β (10 ng/ml) with different concentrations of SA in vitro. Our study revealed that SA could inhibit the IL-1β-induced production of nitric oxide (NO) and prostaglandin E2 (PGE2). Consistent with these findings, the increased protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase (Cox)-2 could also be downregulated by SA. Moreover, SA could also suppress the IL-1β-induced expression of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) in chondrocytes. Furthermore, our data found that SA could suppress the IL-1β-induced mitogen-activated protein kinase (MAPK) pathway activation. In general, this paper elucidates that sinapic acid inhibits the IL-1β-induced inflammation via MAPK pathways and may be a good agent for the treatment of OA.
KEY WORDSosteoarthritis iNOS Cox-2 MMPs ADAMTS5 MAPK
Compliance with Ethical Standards
All animal experiment procedures used in this study complied with the guidelines of the Animal Care and Use Committee of Tongji Medical College, Wuhan, China.
Conflict of Interest
The authors declare that they have no conflict of interest.
- 4.Wallace, I.J., S. Worthington, D.T. Felson, R.D. Jurmain, K.T. Wren, H. Maijanen, R.J. Woods, and D.E. Lieberman. 2017. Knee osteoarthritis has doubled in prevalence since the mid-20th century. Proceedings of the National Academy of Sciences of the United States of America 114 (35): 9332–9336. https://doi.org/10.1073/pnas.1703856114.CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Charlier, E., B. Relic, C. Deroyer, O. Malaise, S. Neuville, J. Collee, M.G. Malaise, and D. De Seny. 2016. Insights on molecular mechanisms of chondrocytes death in osteoarthritis. International Journal of Molecular Sciences 17 (12). https://doi.org/10.3390/ijms17122146.
- 11.Andreasen, M.F., A.K. Landbo, L.P. Christensen, A. Hansen, and A.S. Meyer. 2001. Antioxidant effects of phenolic rye (Secale cereale L.) extracts, monomeric hydroxycinnamates, and ferulic acid dehydrodimers on human low-density lipoproteins. Journal of Agricultural and Food Chemistry 49 (8): 4090–4096.CrossRefPubMedGoogle Scholar
- 12.Balaji, C., J. Muthukumaran, and N. Nalini. 2015. Effect of sinapic acid on 1,2 dimethylhydrazine induced aberrant crypt foci, biotransforming bacterial enzymes and circulatory oxidative stress status in experimental rat colon carcinogenesis. Bratislavské Lekárske Listy 116 (9): 560–566.PubMedGoogle Scholar
- 13.Silambarasan, T., J. Manivannan, M. Krishna Priya, N. Suganya, S. Chatterjee, and B. Raja. 2014. Sinapic acid prevents hypertension and cardiovascular remodeling in pharmacological model of nitric oxide inhibited rats. PLoS One 9 (12): e115682. https://doi.org/10.1371/journal.pone.0115682.CrossRefPubMedPubMedCentralGoogle Scholar
- 14.Silambarasan, T., J. Manivannan, B. Raja, and S. Chatterjee. 2016. Prevention of cardiac dysfunction, kidney fibrosis and lipid metabolic alterations in l-NAME hypertensive rats by sinapic acid—role of HMG-CoA reductase. European Journal of Pharmacology 777: 113–123. https://doi.org/10.1016/j.ejphar.2016.03.004.CrossRefPubMedGoogle Scholar
- 15.Yun, K.J., D.J. Koh, S.H. Kim, S.J. Park, J.H. Ryu, D.G. Kim, J.Y. Lee, and K.T. Lee. 2008. Anti-inflammatory effects of sinapic acid through the suppression of inducible nitric oxide synthase, cyclooxygase-2, and proinflammatory cytokines expressions via nuclear factor-kappaB inactivation. Journal of Agricultural and Food Chemistry 56 (21): 10265–10272. https://doi.org/10.1021/jf802095g.CrossRefPubMedGoogle Scholar
- 16.Pan, T., D. Wu, N. Cai, R. Chen, X. Shi, B. Li, and J. Pan. 2017. Alpha-mangostin protects rat articular chondrocytes against IL-1beta-induced inflammation and slows the progression of osteoarthritis in a rat model. International Immunopharmacology 52: 34–43. https://doi.org/10.1016/j.intimp.2017.08.010.CrossRefPubMedGoogle Scholar
- 17.Tang, Q., Z. Feng, M. Tong, J. Xu, G. Zheng, L. Shen, P. Shang, Y. Zhang, and H. Liu. 2017. Piceatannol inhibits the IL-1beta-induced inflammatory response in human osteoarthritic chondrocytes and ameliorates osteoarthritis in mice by activating Nrf2. Food & Function. https://doi.org/10.1039/c7fo00822h.
- 20.Zheng, W., Z. Tao, L. Cai, C. Chen, C. Zhang, Q. Wang, X. Ying, W. Hu, and H. Chen. 2017. Chrysin attenuates IL-1beta-induced expression of inflammatory mediators by suppressing NF-kappaB in human osteoarthritis chondrocytes. Inflammation 40 (4): 1143–1154. https://doi.org/10.1007/s10753-017-0558-9.CrossRefPubMedGoogle Scholar
- 23.Girotti, A.W. 2016. Modulation of the anti-tumor efficacy of photodynamic therapy by nitric oxide. Cancers (Basel) 8 (10). https://doi.org/10.3390/cancers8100096.
- 28.Selim, K.A., H. Abdelrasoul, M. Aboelmagd, and A.M. Tawila. 2017. The role of the MAPK signaling, topoisomerase and dietary bioactives in controlling cancer incidence. Diseases 5 (2). https://doi.org/10.3390/diseases5020013.
- 29.Li, X., Y. Guo, S. Huang, M. He, Q. Liu, W. Chen, M. Liu, D. Xu, and P. He. 2017. Coenzyme Q10 prevents the interleukin-1 beta induced inflammatory response via inhibition of MAPK signaling pathways in rat articular chondrocytes. Drug Development Research. https://doi.org/10.1002/ddr.21412.
- 30.Feng, Z., X. Li, J. Lin, W. Zheng, Z. Hu, J. Xuan, W. Ni, and X. Pan. 2017. Oleuropein inhibits the IL-1beta-induced expression of inflammatory mediators by suppressing the activation of NF-kappaB and MAPKs in human osteoarthritis chondrocytes. Food & Function 8 (10): 3737–3744. https://doi.org/10.1039/c7fo00823f.CrossRefGoogle Scholar