Abstract
Veratric acid, one of the major benzoic acid isolated from vegetables and fruits, has been reported to have anti-inflammatory activity. The purpose of this study was to investigate the anti-inflammatory effects of veratric acid on lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs). HGFs were pretreated with veratric acid 1 h before LPS stimulation. The productions of IL-6 and IL-8 were detected by ELISA. The expression of iNOS, COX-2, PI3K, AKT, and NF-κB were detected by western blotting. The results showed that veratric acid inhibited LPS-induced IL-6 and IL-8 production, as well as iNOS and COX-2 expression. Veratric acid also inhibited LPS-induced NF-κB activation. In addition, veratric acid was found to suppress LPS-induced PI3K and AKT phosphorylation. In conclusion, the anti-inflammatory mechanism of veratric acid is due to its ability to inhibit PI3K/Akt/NF-κB signaling pathway.
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Assuma, R., T. Oates, D. Cochran, S. Amar, and D.T. Graves. 1998. IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. Journal of Immunology 160: 403–409.
Birkedal-Hansen, H. 1993. Role of cytokines and inflammatory mediators in tissue destruction. Journal of Periodontal Research 28: 500–510.
Bodet, C., F. Chandad, and D. Grenier. 2007. Cranberry components inhibit interleukin-6, interleukin-8, and prostaglandin E production by lipopolysaccharide-activated gingival fibroblasts. European Journal of Oral Sciences 115: 64–70.
Cheng, J.C.H., C.H. Chou, M.L. Kuo, and C.Y. Hsieh. 2006. Radiation-enhanced hepatocellular carcinoma cell invasion with MMP-9 expression through PI3K/Akt/NF-kappa B signal transduction pathway. Oncogene 25: 7009–7018.
Choi, W.S., Y.B. Seo, P.G. Shin, W.Y. Kim, S.Y. Lee, Y.J. Choi, and G.D. Kim. 2015. Veratric acid inhibits iNOS expression through the regulation of PI3K activation and histone acetylation in LPS-stimulated RAW264.7 cells. International Journal of Molecular Medicine 35: 202–210.
Choi, W.S., P.G. Shin, J.H. Lee, and G.D. Kim. 2012. The regulatory effect of veratric acid on NO production in LPS-stimulated RAW264.7 macrophage cells. Cellular Immunology 280: 164–170.
Doyle, C.J., Fitzsimmons, T.R., Marchant, C., Dharmapatni, A.A., Hirsch, R., Bartold, P.M. 2014. Azithromycin suppresses P. gingivalis LPS-induced pro-inflammatory cytokine and chemokine production by human gingival fibroblasts in vitro. Clinical oral investigations.
Fu, Y.H., E.S. Zhou, Z.K. Wei, W. Wang, T.C. Wang, Z.T. Yang, and N.S. Zhang. 2014. Cyanidin-3-O-beta-glucoside ameliorates lipopolysaccharide-induced acute lung injury by reducing TLR4 recruitment into lipid rafts. Biochemical Pharmacology 90: 126–134.
Georganas, C., H. Liu, H. Perlman, A. Hoffmann, B. Thimmapaya, and R.M. Pope. 2000. Regulation of IL-6 and IL-8 expression in rheumatoid arthritis synovial fibroblasts: the dominant role for NF-kappa B but not C/EBP beta or c-Jun. Journal of Immunology 165: 7199–7206.
Herath, T.D., Y. Wang, C.J. Seneviratne, Q. Lu, R.P. Darveau, C.Y. Wang, and L. Jin. 2011. Porphyromonas gingivalis lipopolysaccharide lipid a heterogeneity differentially modulates the expression of IL-6 and IL-8 in human gingival fibroblasts. Journal of Clinical Periodontology 38: 694–701.
Hu, P., P. Huang, and M.W. Chen. 2013. Curcumin attenuates cyclooxygenase-2 expression via inhibition of the NF-kappaB pathway in lipopolysaccharide-stimulated human gingival fibroblasts. Cell Biology International 37: 443–448.
Jefferson, K.K., M.F. Smith, and D.A. Bobak. 1999. Roles of intracellular calcium and NF-kappa B in the clostridium difficile toxin a-induced up-regulation and secretion of IL-8 from human monocytes. Journal of Immunology 163: 5183–5191.
Kinane, D.F. 2001. Causation and pathogenesis of periodontal disease. Periodontology 2000(25): 8–20.
Masada, M.P., R. Persson, J.S. Kenney, S.W. Lee, R.C. Page, and A.C. Allison. 1990. Measurement of interleukin-1 alpha and -1 beta in gingival crevicular fluid: implications for the pathogenesis of periodontal disease. Journal of Periodontal Research 25: 156–163.
Ohtsuji, M., Q. Lin, K. Nishikawa, N. Ohtsuji, H. Okazaki, H. Tsurui, H. Amano, T. Shirai, N. Nishimoto, H. Nishimura, and S. Hirose. 2015. IL-6 signal blockade ameliorates the enhanced osteoclastogenesis and the associated joint destruction in a novel FcgammaRIIB-deficient rheumatoid arthritis mouse model. Modern rheumatology the Japan Rheumatism Association 25: 270–277.
Okada, H., and S. Murakami. 1998. Cytokine expression in periodontal health and disease. Critical Reviews in Oral biology and Medicine : An Official Publication of the American Association of Oral Biologists 9: 248–266.
Page, R.C. 1991. The role of inflammatory mediators in the pathogenesis of periodontal disease. Journal of Periodontal Research 26: 230–242.
Philpott, D.J., S. Yamaoka, A. Israel, and P.J. Sansonetti. 2000. Invasive Shigella flexneri activates NF-kappa B through a lipopolysaccharide-dependent innate intracellular response and leads to IL-8 expression in epithelial cells. Journal of Immunology 165: 903–914.
Raja, B., M. Saravanakumar, and G. Sathya. 2012. Veratric acid ameliorates hyperlipidemia and oxidative stress in Wistar rats fed an atherogenic diet. Molecular and Cellular Biochemistry 366: 21–30.
Shin, S.W., E. Jung, S. Kim, K.E. Lee, J.K. Youm, and D. Park. 2013. Antagonist effects of veratric acid against UVB-induced cell damages. Molecules 18: 5405–5419.
Silva, T.A., G.P. Garlet, S.Y. Fukada, J.S. Silva, and F.Q. Cunha. 2007. Chemokines in oral inflammatory diseases: apical periodontitis and periodontal disease. Journal of Dental Research 86: 306–319.
Slots, J., and M. Ting. 1999. Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in human periodontal disease: occurrence and treatment. Periodontology 2000(20): 82–121.
Song, L.B., H.P. Xiong, J. Li, W.T. Liao, L. Wang, J.H. Wu, and M.F. Li. 2011. Sphingosine kinase-1 enhances resistance to apoptosis through activation of PI3K/Akt/NF-kappa B pathway in human non-small cell lung cancer. Clinical Cancer Research 17: 1839–1849.
Sun, Y., Y. Zhao, J. Yao, L. Zhao, Z. Wu, Y. Wang, D. Pan, H. Miao, Q. Guo, and N. Lu. 2015. Wogonoside protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting NF-kappaB and NLRP3 inflammasome activation. Biochemical Pharmacology 94: 142–154.
Van Dyke, T.E., and C.N. Serhan. 2003. Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseases. Journal of Dental Research 82: 82–90.
Wang, P.L., K. Ohura, T. Fujii, M. Oido-Mori, Y. Kowashi, M. Kikuchi, Y. Suetsugu, and J. Tanaka. 2003. DNA microarray analysis of human gingival fibroblasts from healthy and inflammatory gingival tissues. Biochemical and Biophysical Research Communications 305: 970–973.
Wang, P.L., K. Sato, M. Oido, T. Fujii, Y. Kowashi, M. Shinohara, K. Ohura, H. Tani, and Y. Kuboki. 1998. Involvement of CD14 on human gingival fibroblasts in Porphyromonas gingivalis lipopolysaccharide-mediated interleukin-6 secretion. Archives of Oral Biology 43: 687–694.
Yee, M., S. Kim, P. Sethi, N. Duzgunes, and K. Konopka. 2014. Porphyromonas gingivalis stimulates IL-6 and IL-8 secretion in GMSM-K, HSC-3 and H413 oral epithelial cells. Anaerobe 28: 62–67.
Yiemwattana, I., Kaomongkolgit, R. 2014. Alpha-mangostin suppresses IL-6 and IL-8 expression in P. gingivalis LPS-stimulated human gingival fibroblasts. Odontology/the Society of the Nippon Dental University.
Zdarilova, A., A. Svobodova, V. Simanek, and J. Ulrichova. 2009. Prunella vulgaris extract and rosmarinic acid suppress lipopolysaccharide-induced alteration in human gingival fibroblasts. Toxicology In Vitro : An International Journal Published in Association with BIBRA 23: 386–392.
Zdarilova, A., A. Svobodova, V. Simanek, and J. Ulrichova. 2009. Prunella vulgaris extract and rosmarinic acid suppress lipopolysaccharide-induced alteration in human gingival fibroblasts. Toxicology in Vitro 23: 386–392.
Acknowledgments
This study was supported by “Health Science and Technology Development Program Project of Jinan” (no. 2011-14) and “Science and Technology Development Program Project of Jinan” (no. 201401082).
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The authors declare that they have no competing interests.
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Wang, Qb., Sun, Ly., Gong, Zd. et al. Veratric Acid Inhibits LPS-Induced IL-6 and IL-8 Production in Human Gingival Fibroblasts. Inflammation 39, 237–242 (2016). https://doi.org/10.1007/s10753-015-0243-9
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DOI: https://doi.org/10.1007/s10753-015-0243-9