Eriodictyol Suppresses Porphyromonas gingivalis-Induced Reactive Oxygen Species Production by Gingival Keratinocytes and the Inflammatory Response of Macrophages

Patricia Milagros Maquera-Huacho; Denise Palomari Spolidorio; John A Manthey; Daniel Grenier

doi:10.3389/froh.2022.847914

Eriodictyol Suppresses Porphyromonas gingivalis-Induced Reactive Oxygen Species Production by Gingival Keratinocytes and the Inflammatory Response of Macrophages

Front Oral Health. 2022 Feb 28:3:847914. doi: 10.3389/froh.2022.847914. eCollection 2022.

Authors

Patricia Milagros Maquera-Huacho^{1

2}, Denise Palomari Spolidorio², John A Manthey³, Daniel Grenier¹

Affiliations

¹ Oral Ecology Research Group, Faculty of Dentistry, Université Laval, Quebec City, QC, Canada.
² Department of Physiology and Pathology, School of Dentistry, São Paulo State University (Unesp), Araraquara, Brazil.
³ U.S. Horticultural Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture (USDA), Fort Pierce, FL, United States.

Abstract

Porphyromonas gingivalis is a key pathogen of periodontitis, an inflammatory disease that affects the tooth-supporting tissues. The aim of the present study was to investigate the effects of the flavanone eriodictyol on P. gingivalis-induced reactive oxygen species (ROS) production by gingival keratinocytes and the inflammatory response of macrophages. Porphyromonas gingivalis and H₂O₂ acted synergistically to induce ROS production by keratinocytes. The presence of eriodictyol significantly attenuated ROS production in a dose-dependent manner. We used a macrophage model to show that eriodictyol decreases the secretion of IL-1β, IL-6, IL-8, and TNF-α induced by P. gingivalis. Evidence has been brought that this anti-inflammatory property of eriodictyol may be related to its ability to prevent the activation of the NF-κB signaling pathway by P. gingivalis. This periodontal pathogen was also found to be a potent inducer of matrix metalloproteinase (MMP) production by macrophages, including MMP-2, MMP-8, and MMP-9. Eriodictyol dose-dependently inhibited the production of all three MMPs. Lastly, eriodictyol inhibited the catalytic activity of both MMP-9 and P. gingivalis collagenase. In conclusion, eriodictyol may be a potential therapeutic agent for preventing and/or treating periodontal disease due to its antioxidant, anti-inflammatory, and anti-proteinase properties.

Keywords: Porphyromonas gingivalis; eriodictyol; keratinocyte; macrophage; periodontal disease.