Proliferative and Anti-Inflammatory Effects of Resveratrol and Silymarin on Human Gingival Fibroblasts: A View to the Future
Abstract
Objectives: It has been demonstrated that polyphenol components such as silymarin and resveratrol have anti-inflammatory properties. Periodontitis is a chronic inflammatory disease that leads to the breakdown of dental supporting tissues and tooth loss. The purpose of this study was to investigate the anti-inflammatory effects of silymarin and resveratrol on lipopolysaccharide (LPS)-induced inflammatory response in human gingival fibroblasts (HGFs).
Materials and Methods: HGFs were treated with different concentrations of silymarin and/or resveratrol (25, 50, 100 and 200μg/ml). The effects of silymarin and resveratrol on cell viability and proliferation were assessed by MTT assay and cell cycle analysis, respectively. Also, HGFs were treated with silymarin and/or resveratrol and were stimulated with LPS. The levels of Interleukin-6 (IL-6) and IL-8 were assessed by enzyme-linked immunosorbent assay (ELISA).
Results: After treatment with silymarin, the viability of fibroblasts significantly increased, whereas treatment with resveratrol did not have any significant effect on cell viability. However, the combination of these flavonoids (50µg/ml silymarin and 100µg/ml resveratrol) significantly increased the viability of fibroblasts. Resveratrol significantly inhibited LPS-induced IL-6 and IL-8 secretion by HGFs, but silymarin did not show such a significant effect.
Conclusions: The findings of the present study demonstrated the anti-inflammatory effects of resveratrol and its combination with silymarin. Therefore, the combination of silymarin and resveratrol may be useful as a therapeutic agent for treatment of periodontal diseases.
- Bonifait L, Grenier D. Cranberry polyphenols: potential benefits for dental caries and periodontal disease. J Can Dent Assoc. 2010;76:a130.
- Labrecque J, Bodet C, Chandad F, Grenier D. Effects of a high-molecular-weight cranberry fraction on growth, biofilm formation and adherence of porphyromonas gingivalis. J Antimicrob Chemother. 2006 Aug;58(2): 439-43.
- Cazalis J, Tanabe S, Gagnon G, Sorsa T, Grenier D. Tetracyclines and chemically modified tetracycline-3 (CMT-3) modulate cytokine secretion by lipopolysaccharide-stimulated whole blood. Inflammation. 2009 Apr;32(2):130-7.
- La VD, Howell AB, Grenier D. Anti-porphyromonas gingivalis and anti-inflammatory activities of A-type cranberry proanthocyanidins. Antimicrob Agents Chemother. 2010 May;54(5):1778-84.
- Scalbert A, Johnson IT, Saltmarsh M. Polyphenols: antioxidants and beyond. Am J Clin Nutr. 2005 Jan;81(1 Suppl):215S-217S.
- Shahidi M, Jafari S, Barati M, Mahdipour M, Gholami MS. Predictive value of salivary microRNA-320a, vascular endothelial growth factor receptor 2, CRP and IL-6 in oral lichen planus progression. Inflammopharmacology. 2017 May 13.
- Torkzaban P, Pourabbas R, Hajilooi M, Jafari F, Zarandi A. Evaluating the effect of one stage full mouth disinfection on serum IL-17 and IL-23 levels in patients with moderate to severe chronic periodontitis. Med J Tabriz Univ Med Sci Health Serv. 2014 Feb–Mar;35(6): 20-25.
- Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CW, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997 Jan;275(5297):218-20.
- Csaki C, Mobasheri A, Shakibaei M. Synergistic chondroprotective effects of curcumin and resveratrolin human articular chondrocytes: inhibition of IL-1beta-induced NF-kappaB-mediated inflammation and apoptosis. Arthritis Res Ther. 2009;11(6):R165.
- Manna SK, Mukhopadhyay A, Aggarwal BB. Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-kappaB, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol. 2000 Jun15;164(12):6509-19.
- Csaki C, Keshishzadeh N, Fischer K, Shakibaei M. Regulation of inflammation signaling by resveratrol in human chondrocytes in vitro. Biochem Pharmacol. 2008 Feb1;75(3):677-87.
- Malejka-Giganti D, Bennett KK, Culp SJ, Beland FA, Shinozuka H, Bliss RL. Suppression of 7,12-dimethylbenz [a]anthracene-induced mammary carcinogenesis by
pre-initiation treatment of rats with beta-naphthoflavone coincides with decreased levels of the carcinogen-derived DNA adducts in the mammary gland. Cancer Detect Prev. 2005;29(4):338-47.
- Bereswill S, Munoz M, Fischer A, Plickert R, Haag LM, Otto B, et al. Anti-inflammatory effects of resveratrol, curcumin and simvastatin in acute small intestinal inflammation. PLoS One. 2010 Dec3;5(12): e15099.
- Zhu X, Liu Q, Wang M, Liang M, Yang X, Xu X, et al. Activation of Sirt1 by resveratrol inhibits TNF-alpha induced inflammation in fibroblasts. PLoS One. 2011;6(11):e27081.
- De La Puerta R, Martinez E, Bravo L, Ahumada MC. Effect of silymarin on different acute inflammation models and on leukocyte migration. J Pharm Pharmacol. 1996 Sep;48(9):968-70.
- Flora K, Hahn M, Rosen H, Benner K. Milk thistle (silybum marianum) for the therapy of liver disease. Am J Gastroenterol. 1998 Feb;93(2):139-43.
- Jamshidi A, Ahmadi Ashtiani HR, Oliazadeh N, Jafarzadrh N, Taheri Brojerdi M, Naderi M. A key for thousands locks. Noaavar Press. 2007;70-87:12.
- Manna SK, Mukhopadhyay A, Van NT, Aggarwal BB. Silymarin suppresses TNF-induced activation of NF-kappaB, c-Jun N-terminal kinase, and apoptosis. J Immunol. 1999 Dec15;163(12):6800-9.
- Saliou C, Kitazawa M, McLaughlin L, Yang JP, Lodge JK, Tetsuka T, et al. Antioxidants modulate acute solar ultraviolet radiation-induced NF-kappa-B activation in a human keratinocyte cell line. Free Radic Biol Med. 1999 Jan;26(1-2):174-83.
- Saliou C, Rihn B, Cillard J, Okamoto T, Packer L. Selective inhibition of NF-kappaB activation by the flavonoid hepatoprotector silymarin in HepG2. Evidence for different activating pathways. FEBS lett. 1998 Nov27;440(1-2):8-12.
- Sharifi R, Rastegar H, Kamalinejad M, Dehpour AR, Tavangar SM, Paknejad M, et al. Effect of topical application of silymarin (silybum marianum) on excision wound healing in albino rats. Acta Med Iran. 2012;50(9): 583-8.
- Altaei T. The treatment of melasma by silymarin cream. BMC Dermatol. 2012 Oct2;12(1):18.
- Torkzaban P, Saffarpour A, Bidgoli M, Sohilifar S. In vitro evaluation of isolation possibility of stem cells from intraoral soft tissue and comparison of them with bone marrow stem cells. J Dent (Tehran). 2012 Winter; 9(1):1-6.
- Van Dyke TE, Serhan CN. Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseases. J Dent Res. 2003 Feb;82(2):82-90.
- Mahmudpourmoteshakker T, Rafiee E, Farhad S, Aminzadeh A. Comparison of the effect of doxycycline and licorice on chronic periodontitis- a clinical trial study. J Res Dent Sci. 2014;11(3):123-9.
- Ahmadi Ashtiani HR, Allameh A, Hamidipour N, Rastegar H, Soleimani M. Increasing rate of human bone marrow mesenchymal stem cell proliferation in the presence of silymarin. J Med Plants. 2010;9(34):156-64.
- Morishima C, Shuhart MC, Wang CC, Paschal DM, Apodaca MC, Liu Y, et al. Silymarin inhibits in vitro T-cell proliferation and cytokine production in hepatitis C virus infection. Gastroenterology. 2010 Feb 28;138(2): 671-81.
- San Miguel SM, Opperman LA, Allen EP, Zielinski J, Svoboda KK. Bioactive polyphenol antioxidants protect oral fibroblasts from ROS-inducing agents. Arch Oral Biol. 2012 Dec;57(12):1657-67.
- Daghigh F, Borghaei RC, Thornton RD, Bee JH.
Human gingival fibroblasts produce nitric oxide in response to proinflammatory cytokines. J Periodontol. 2002 Apr;73(4):392-400.
- Katiyar SK, Roy AM, Baliga MS. Silymarin induces apoptosis primarily through a p53-dependent pathway involving Bcl-2/Bax, cytochrome c release, and caspase activation. Mol Cancer Ther. 2005 Feb;4(2):207-16.
- Rizzo A, Bevilacqua N, Guida L, Annunziata M, Romano Carratelli C, Paolillo R. Effect of resveratrol and modulation of cytokine production on human periodontal ligament cells. Cytokine. 2012 Oct;60(1):197-204.
- Stivala LA, Savio M, Carafoli F, Perucca P, Bianchi L, Maga G, et al. Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol. J Biol Chem. 2001 Jun 22;276(25): 22586-94.
- Sgambato A, Ardito R, Faraglia B, Boninsegna A, Wolf FI, Cittadini A. Resveratrol, a natural phenolic compound, inhibits cell proliferation and prevents oxidative DNA damage. Mutat Res. 2001 Sep 20;496(1): 171-80.
- Biesalski HK. Polyphenols and inflammation: basic interactions. Curr Opin Clin Nutr Metab Care. 2007 Nov;10(6):724-8.
- Kramer HF, Goodyear LJ. Exercise, MAPK, and NF-kappaB signaling in skeletal muscle. J Appl Physiol (1985). 2007 Jul;103(1):388-95.
- Rahman I, Biswas SK, Kirkham PA. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem Pharmacol. 2006 Nov30;72(11): 1439-52.
- Olson ER, Naugle JE, Zhang X, Bomser JA, Meszaros JG. Inhibition of cardiac fibroblast proliferation and myofibroblast differentiation by resveratrol. Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1131-8.
- Lu X, Ma L, Ruan L, Kong Y, Mou H, Zhang Z, et al. Resveratrol differentially modulates inflammatory responses of microglia and astrocytes. J Neuroinflammation. 2010 Aug 7;7:46.
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Issue | Vol 14, No 4 (2017) | |
Section | Original Article | |
Keywords | ||
Resveratrol Silymarin Fibroblasts Interleukin-6 Interleukin-8 |
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