Keywords
Bone Resorption
Resveratrol
How to Cite
Abstract
Introduction: Resveratrol (RSV) is a natural polyphenol with anti-inflammatory and antioxidant properties, widely studied for its therapeutic potential in chronic inflammatory diseases. Periodontitis is a multifactorial condition characterized by the progressive destruction of tooth-supporting tissues, resulting from an exacerbated immune response and the accumulation of reactive oxygen species, and in this context RSV emerges as a potential modulator of the inflammatory response. Methodology: An integrative review of preclinical literature was conducted to evaluate the effects of RSV on the progression of experimental periodontitis in animal models, with emphasis on alveolar bone loss (ABL) and the molecular mechanisms involved. The search was carried out in the PubMed and LILACS databases, following PRISMA 2020 guidelines, using the descriptors “periodontitis,” “periodontal disease,” and “resveratrol.” In vivo studies that used ligature to induce the disease, with standardized RSV administration and ABL assessment, were included. Results and Discussion: Of the 170 articles initially identified, 11 met the inclusion criteria, all using rats with ligature-induced periodontitis. RSV was administered orally, by gavage, or by injection, at doses ranging from 10 to 25 mg/kg, for periods between 7 and 70 days. Ten studies reported a significant reduction in ABL, associated with the modulation of inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-17), increased IL-4 levels, and inhibition of the NF-κB, TLR4, p38 MAPK, and NADPH oxidase pathways. The therapeutic effect was also observed in models associated with diabetes, arthritis, osteoporosis, and cigarette smoke exposure, while only one study found no significant difference, possibly due to the short intervention period. Conclusions: RSV demonstrated a protective effect against alveolar bone loss through anti-inflammatory and antioxidant mechanisms, standing out as a promising adjuvant agent in periodontal therapy; however, randomized clinical trials are still needed to validate its efficacy, safety, optimal dosage, and molecular mechanisms in humans.
References
Shaito A, Posadino AM, Younes N, Hasan H, Halabi S, Alhababi D, et al. Potential Adverse Effects of Resveratrol: A Literature Review. Int J Mol Sci. 2020 Mar 18;21(6):2084.
Salehi B, Mishra AP, Nigam M, Sener B, Kilic M, Sharifi-Rad M, et al. Resveratrol: A Double-Edged Sword in Health Benefits. Biomedicines. 2018 Sep 9;6(3):91.
Kundu JK, Surh YJ. Cancer chemopreventive and therapeutic potential of resveratrol: mechanistic perspectives. Cancer Lett. 2008 Oct 8;269(2):243–61.
Könönen E, Gursoy M, Gursoy UK. Periodontitis: A Multifaceted Disease of Tooth-Supporting Tissues. J Clin Med. 2019 Jul 31;8(8):1135.
J M, I C. Molecular aspects of the pathogenesis of periodontitis. Periodontol 2000. 2015 Oct;69(1). Disponível em: https://pubmed.ncbi.nlm.nih.gov/26252398/
Belibasakis GN, Bostanci N. The RANKL-OPG system in clinical periodontology. J Clin Periodontol. 2012 Mar;39(3):239–48.
Shang J, Liu H, Zheng Y, Zhang Z. Role of oxidative stress in the relationship between periodontitis and systemic diseases. Front Physiol. 2023 Jul 12;14:1210449.
Nikniaz S, Vaziri F, Mansouri R. Impact of resveratrol supplementation on clinical parameters and inflammatory markers in patients with chronic periodontitis: a randomized clinical trial. BMC Oral Health. 2023 Mar 27;23:177.
Zhang Q, Xu S, Xu W, Zhou Y, Luan H, Wang D. Resveratrol decreases local inflammatory markers and systemic endotoxin in patients with aggressive periodontitis. Medicine (Baltimore). 2022 Jun 24;101(25):e29393.
Andrade EF, Orlando DR, Araújo AMS, de Andrade JNBM, Azzi DV, de Lima RR, et al. Can Resveratrol Treatment Control the Progression of Induced Periodontal Disease? A Systematic Review and Meta-Analysis of Preclinical Studies. Nutrients. 2019 May;11(5). Disponível em: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566182
Oz HS, Puleo DA. Animal Models for Periodontal Disease. J Biomed Biotechnol. 2011;2011:754857.
Graves DT, Fine D, Teng YTA, Van Dyke TE, Hajishengallis G. The Use of Rodent Models to Investigate Host-Bacteria Interactions Related to Periodontal Diseases. J Clin Periodontol. 2008 Feb;35(2):89–105.
PRISMA statement. PRISMA 2020 statement. [cited 2025 Jul 28]. Disponível em: https://www.prisma-statement.org/prisma-2020
Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Syst Rev. 2016 Dec;5(1):210. doi: 10.1186/s13643-016-0384-4.
Giménez-Siurana A, Gómez García F, Pagan Bernabeu A, Lozano-Pérez AA, Aznar-Cervantes SD, Cenis JL, et al. Chemoprevention of Experimental Periodontitis in Diabetic Rats with Silk Fibroin Nanoparticles Loaded with Resveratrol. Antioxidants. 2020 Jan;9(1):85.
Cirano FR, Casarin RCV, Ribeiro FV, Casati MZ, Pimentel SP, Taiete T, et al. Effect of Resveratrol on periodontal pathogens during experimental periodontitis in rats. Braz Oral Res. 2016 Nov 28;30(1):e128.
Li Y, Huang Z, Pan S, Feng Y, He H, Cheng S, et al. Resveratrol Alleviates Diabetic Periodontitis-Induced Alveolar Osteocyte Ferroptosis Possibly via Regulation of SLC7A11/GPX4. Nutrients. 2023 Apr 28;15(9):2115.
Wagner MC, Cavagni J, Gaio EJ, Brum VS, Jesus LH, Filho MS, et al. Effect of red wine and its major components on periodontitis and systemic inflammation in rats. J Int Acad Periodontol. 2019 Oct 1;21(4):139–47.
Casati MZ, Algayer C, Cardoso da Cruz G, Ribeiro FV, Casarin RCV, Pimentel SP, et al. Resveratrol decreases periodontal breakdown and modulates local levels of cytokines during periodontitis in rats. J Periodontol. 2013 Mar;84(10):e58–64.
Tamaki N, R COC, Y I, M F, T N, Ho I. Resveratrol improves oxidative stress and prevents the progression of periodontitis via the activation of the Sirt1/AMPK and the Nrf2/antioxidant defense pathways in a rat periodontitis model. Free Radic Biol Med. 2014 Oct;75. Disponível em: https://pubmed.ncbi.nlm.nih.gov/25091897/
Zhen L, Ds F, Y Z, Xm C, Lm W. Resveratrol ameliorates experimental periodontitis in diabetic mice through negative regulation of TLR4 signaling. Acta Pharmacol Sin. 2015 Feb;36(2). Disponível em: https://pubmed.ncbi.nlm.nih.gov/25530164/
Bhattarai G, Poudel SB, Kook SH, Lee JC. Resveratrol prevents alveolar bone loss in an experimental rat model of periodontitis. Acta Biomater. 2016;29:398–408.
Ribeiro FV, Pimentel DS, Feres-Filho FC, Bastos BB, Teles H, Daibert J, et al. Resveratrol Inhibits Periodontitis-Related Bone Loss in Rats Subjected to Cigarette Smoke Inhalation. J Periodontol. 2017 Aug;88(8). Disponível em: https://pubmed.ncbi.nlm.nih.gov/28492360/
Ikeda E, Ikeda Y, Wang Y, Fine N, Sheikh Z, Viniegra A, et al. Resveratrol derivative-rich melinjo seed extract induces healing in a murine model of established periodontitis. J Periodontol. 2018 Jun;89(5):586–95.
Chin YT, Hsieh MT, Lin CY, Kuo PJ, Yang YCSH, Shih YJ, et al. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-glucoside Isolated from Polygoni Multiflori Ameliorates the Development of Periodontitis. Mediators Inflamm. 2016 Jul 18;2016:6953459.
Molez AM, do Nascimento EHL, Haiter Neto F, Cirano FR, Pimentel SP, Ribeiro FV, et al. Effect of resveratrol on the progression of experimental periodontitis in an ovariectomized rat model of osteoporosis: Morphometric, immune-enzymatic, and gene expression analysis. J Periodontal Res. 2020 Sep;55(6):840–9.
Corrêa MG, Pires PR, Ribeiro FV, Pimentel SZ, Casarin RCV, Cirano FR, et al. Systemic treatment with resveratrol and/or curcumin reduces the progression of experimental periodontitis in rats. J Periodontal Res. 2017;52(2):201–9.
Corrêa MG, Pires PR, Ribeiro FV, Pimentel SP, Casarin RCV, Cirano FR, et al. Systemic treatment with resveratrol reduces the progression of experimental periodontitis and arthritis in rats. PLoS One. 2018 Oct 10;13(10). Disponível em: https://pubmed.ncbi.nlm.nih.gov/30281626/
Corrêa MG, Saadi A, Holanda T, Ribeiro FV, Cirano FR, Casati MZ, et al. Resveratrol attenuates oxidative stress during experimental periodontitis in rats exposed to cigarette smoke inhalation. J Periodontal Res. 2019 Jun;54(3). Disponível em: https://pubmed.ncbi.nlm.nih.gov/30346038/
Van Dyke TE, Dave S. Risk Factors for Periodontitis. J Int Acad Periodontol. 2005 Jan;7(1):3-7.
N N, M K. Cytokines in gingivitis and periodontitis: from pathogenesis to therapeutic targets. Front Immunol. 2024 Aug 26;15. Disponível em: https://pubmed.ncbi.nlm.nih.gov/39253090/
V TTT, C PM, T VP, T JS, L IT. The Promising Role of Antioxidant Phytochemicals in the Prevention and Treatment of Periodontal Disease via the Inhibition of Oxidative Stress Pathways: Updated Insights. Antioxid (Basel). 2020 Dec 12;9(12). Disponível em: https://pubmed.ncbi.nlm.nih.gov/33271934/
C DL. Inflammation and bone loss in periodontal disease. J Periodontol. 2008 Aug;79(8 Suppl). Disponível em: https://pubmed.ncbi.nlm.nih.gov/18673012/
Vitaglione P, Sforza S, Galaverna G, Ghidini C, Caporaso N, Vescovi PP, et al. Bioavailability of trans-resveratrol from red wine in humans. Mol Nutr Food Res. 2005 May;49(5):495–504.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright (c) 2025 Vinicius Curti Morselli Araujo, Gabriel Silva Rezende Freitas, Guilherme Rodrigues Marinho, Amanda Carolina Saraiva, Vitor Henrique Moreira Moreno, Isadora Ribeiro Lino, Kaillainy Bernardes Reis, William Eduardo Pirola, Ana Paula Oliveira de Quadros, Thais Uenoyama Dezem
