Healing effects of monomer and dimer resveratrol in a mouse periodontitis model

Eri Ikeda; Daiki Tanaka; Michael Glogauer; Howard C Tenenbaum; Yuichi Ikeda

doi:10.1186/s12903-022-02499-2

Healing effects of monomer and dimer resveratrol in a mouse periodontitis model

BMC Oral Health. 2022 Nov 1;22(1):460. doi: 10.1186/s12903-022-02499-2.

Authors

Eri Ikeda^{1

2}, Daiki Tanaka³, Michael Glogauer^{4

5}, Howard C Tenenbaum^{4

6}, Yuichi Ikeda³

Affiliations

¹ Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, 113-8549, Bunkyo, Tokyo, Japan. eri.mim@tmd.ac.jp.
² Department of Molecular Immunology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, 113-8549, Bunkyo, Tokyo, Japan. eri.mim@tmd.ac.jp.
³ Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, 113-8549, Bunkyo, Tokyo, Japan.
⁴ Faculty of Dentistry, University of Toronto, 124 Edward St, M5G 1G6, Toronto, ON, Canada.
⁵ Department of Dental Oncology and Maxillofacial Prosthetics University Health Network - Princess Margaret Cancer Centre, 610 University Avenue, M5G 2M9, Toronto, ON, Canada.
⁶ Centre for Advanced Dental Research and Care, Department of Dentistry, Mount Sinai Hospital, 600 University Avenue, M5G 1X5, Toronto, ON, Canada.

Abstract

Background: The antioxidant and anti-inflammatory effects of resveratrol have been reported previously. Particularly, monomeric trans-resveratrol has been demonstrated to produce positive effects in various pathological processes. We reported previously that resveratrol dimer-rich melinjo extract, among others, caused bone healing, decreased local oxidative damage, and activated antioxidants nuclear factor erythroid 2-related factor 2 (Nrf2) pathways in a mouse model of experimentally induced periodontitis (EP). This study aimed to compare the bone-healing effects of the resveratrol monomer to the resveratrol dimer (gnetin C found in melinjo seed extract) in a model of EP and investigate the involvement of Nrf2 for effects of either form of resveratrol.

Methods: EP was induced experimentally in mice by placement of a 9 - 0 silk ligature around the left second molar. Mice received 10 mg/kg of either resveratrol monomer or dimer intraperitoneally on day 15 after induction of EP. The bone level around the ligated teeth was measured over time, and levels of proinflammatory cytokines and oxidative stress were measured in the periodontal tissues around the ligated teeth.

Results: Resveratrol dimer induced greater periodontal bone healing as compared to that related to use of the resveratrol monomer. It appears that healing of periodontal bone in either group was likely related to master regulation of antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) significantly. Downregulation of IL-1β, a proinflammatory cytokine was also demonstrated in the resveratrol dimer group.

Conclusion: Our results showed that administration of resveratrol in either dimer form or the monomeric form reduced periodontal bone loss with greater inhibition of bone loss being demonstrated in the dimer group as compared to the monomer group and that these effects were related in all likelihood to decreased oxidative stress and hence reduction in local inflammation.

Keywords: Inflammation; Periodontitis; Reactive oxygen species; Resveratrol, Melinjo seed extract, Gnetin C, Anti-inflammatory agents.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alveolar Bone Loss*
Animals
Antioxidants / pharmacology
Cytokines / metabolism
Disease Models, Animal
Mice
NF-E2-Related Factor 2
Periodontitis* / metabolism
Resveratrol

Substances

Resveratrol
NF-E2-Related Factor 2
Antioxidants
Cytokines