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

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.

Highlights

Periodontal disease is a current public health problem worldwide that alters the quality of life of patients
We investigated the effects of eriodictyol on P. gingivalis-induced reactive oxygen species (ROS) production by gingival keratinocytes and on the inflammatory response of macrophages
The ability of eriodictyol to impair ROS production by gingival keratinocytes treated with P. gingivalis combined with H2O2, a well-known inducer of oxidative stress [26, 27], was investigated

Summary

Introduction

Periodontal disease is a current public health problem worldwide that alters the quality of life of patients. Periodontitis, a destructive form of periodontal disease, affects nearly 10% of the USA adult population [1]. Periodontitis is defined as an inflammatory disorder of the periodontium triggered by specific anaerobic Gram-negative bacteria, called periodontal pathogens, that colonize the subgingival areas [2, 3]. Eriodictyol and Periodontal Disease to the destruction of tooth-supporting connective tissue and alveolar bone, leading to tooth loss. In addition to the damage caused in the oral cavity, the etiological factors of periodontitis have additional impacts on the whole human body. Associations between periodontitis and cardiovascular diseases, type 2 diabetes, neurodegenerative diseases, and adverse pregnancy outcomes have been reported by numerous studies [4–6]

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