6-Shogaol Inhibits Advanced Glycation End-Products-Induced IL-6 and ICAM-1 Expression by Regulating Oxidative Responses in Human Gingival Fibroblasts.

Nonaka Nonaka,Sakamoto Sakamoto,Naruishi Naruishi,Yumoto Yumoto,Inagaki Inagaki,Kido Kido,Bando Bando

doi:10.3390/molecules24203705

Nonaka Nonaka, Sakamoto Sakamoto + Show 5 more

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https://doi.org/10.3390/molecules24203705

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Journal: Molecules (Basel, Switzerland)	Publication Date: Oct 15, 2019
Citations: 24	License type: CC BY 4.0

Affiliation: Tokushima University

Abstract

Advanced glycation end-products (AGEs) cause diabetes mellitus (DM) complications and accumulate more highly in periodontal tissues of patients with periodontitis and DM. AGEs aggravate periodontitis with DM by increasing the expression of inflammation-related factors in periodontal tissues. 6-Shogaol, a major compound in ginger, has anti-inflammatory and anti-oxidative activities. However, the influence of shogaol on DM-associated periodontitis is not well known. In this study, the effects of 6-shogaol on AGEs-induced oxidative and anti-oxidative responses, and IL-6 and ICAM-1 expression in human gingival fibroblasts (HGFs) were investigated. When HGFs were cultured with 6-shogaol and AGEs, the activities of reactive oxygen species (ROS) and antioxidant enzymes (heme oxygenase-1 [HO-1] and NAD(P)H quinone dehydrogenase 1 [NQO1]), and IL-6 and ICAM-1 expressions were investigated. RAGE expression and phosphorylation of MAPKs and NF-κB were examined by western blotting. 6-Shogaol significantly inhibited AGEs-induced ROS activity, and increased HO-1 and NQO1 levels compared with the AGEs-treated cells. The AGEs-stimulated expression levels of receptor of AGE (RAGE), IL-6 and ICAM-1 and the phosphorylation of p38, ERK and p65 were attenuated by 6-shogaol. These results suggested that 6-shogaol inhibits AGEs-induced inflammatory responses by regulating oxidative and anti-oxidative activities and may have protective effects on periodontitis with DM.

Highlights

Diabetes mellitus (DM) is a major risk factor of periodontal diseases [1]
Hyperglycemia occurs in DM and induces high glycation of proteins by a Maillard reaction, and glycated proteins result in advanced glycation end-products (AGEs) [2]
AGEs bind to a receptor for AGE (RAGE) and increase the expression of pro-inflammatory molecules such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and vascular cell adhesion molecule-1 in some cells [4]

Summary

Introduction

Diabetes mellitus (DM) is a major risk factor of periodontal diseases [1]. Hyperglycemia occurs in DM and induces high glycation of proteins by a Maillard reaction, and glycated proteins result in advanced glycation end-products (AGEs) [2]. AGEs accelerate diabetic complications, including diabetic nephropathy, diabetic cataract, diabetic peripheral neuropathy, and cardiovascular disorders [3]. AGEs bind to a receptor for AGE (RAGE) and increase the expression of pro-inflammatory molecules such as interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and vascular cell adhesion molecule-1 in some cells [4]. AGEs accumulate excessively in periodontal tissues of DM patients compared with non-DM individuals [5] and were detected in epithelial cells, fibroblasts, endothelial cells, and inflammatory cells in periodontal tissues of DM patients [6].

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