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橙皮苷对口腔上皮细胞模型屏障功能和活性氧产生的影响,以及对感染期间巨噬细胞来源的炎症介质分泌的影响。

Effect of Hesperidin on Barrier Function and Reactive Oxygen Species Production in an Oral Epithelial Cell Model, and on Secretion of Macrophage-Derived Inflammatory Mediators during Infection.

机构信息

Oral Ecology Research Group, Faculty of Dentistry, Université Laval, Quebec City, QC G1V 0A6, Canada.

Department of Physiology and Pathology, School of Dentistry, São Paulo State University (Unesp), Araraquara 14801-903, SP, Brazil.

出版信息

Int J Mol Sci. 2023 Jun 20;24(12):10389. doi: 10.3390/ijms241210389.

DOI:10.3390/ijms241210389
PMID:37373533
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10298893/
Abstract

is a periodontopathogenic bacterium that can adhere to and colonize periodontal tissues, leading to an inflammatory process, and, consequently, tissue destruction. New therapies using flavonoids, such as hesperidin, are being studied, and their promising properties have been highlighted. The aim of this study was to evaluate the effect of hesperidin on the epithelial barrier function, reactive oxygen species (ROS) production, and on the inflammatory response caused by in in vitro models. The integrity of the epithelial tight junctions challenged by was determined by monitoring the transepithelial electrical resistance (TER). adherence to a gingival keratinocyte monolayer and a basement membrane model were evaluated by a fluorescence assay. A fluorometric assay was used to determine the ROS production in gingival keratinocytes. The level of pro-inflammatory cytokines and matrix metalloproteinases (MMPs) secretion was evaluated by ELISA; to assess NF-κB activation, the U937-3xjB-LUC monocyte cell line transfected with a luciferase reporter gene was used. Hesperidin protected against gingival epithelial barrier dysfunction caused by and reduced the adherence of to the basement membrane model. Hesperidin dose-dependently inhibited -mediated ROS production by oral epithelial cells as well as the secretion of IL-1β, TNF-α, IL-8, MMP-2, and MMP-9 by macrophages challenged with . Additionally, it was able to attenuate NF-κB activation in macrophages stimulated with . These findings suggest that hesperidin has a protective effect on the epithelial barrier function, in addition to reducing ROS production and attenuating the inflammatory response associated with periodontal disease.

摘要

牙龈卟啉单胞菌是一种牙周致病菌,能够黏附并定植于牙周组织,引发炎症反应,并最终导致组织破坏。目前正在研究使用类黄酮(如橙皮苷)的新疗法,其具有广阔的应用前景。本研究旨在评估橙皮苷对上皮屏障功能、活性氧(ROS)产生以及由牙龈卟啉单胞菌引起的炎症反应的影响。通过监测跨上皮电阻(TER)来确定由 引起的上皮紧密连接完整性。通过荧光测定法评估 对牙龈角质形成细胞单层和基底膜模型的黏附。使用荧光法测定牙龈角质形成细胞中 ROS 的产生。通过 ELISA 评估促炎细胞因子和基质金属蛋白酶(MMPs)分泌水平;为了评估 NF-κB 激活,使用转染了荧光素酶报告基因的 U937-3xjB-LUC 单核细胞系。橙皮苷可防止由 引起的牙龈上皮屏障功能障碍,并减少 对基底膜模型的黏附。橙皮苷剂量依赖性地抑制由口腔上皮细胞产生的 -介导的 ROS 产生以及由 刺激的巨噬细胞中 IL-1β、TNF-α、IL-8、MMP-2 和 MMP-9 的分泌。此外,它还能够减弱由 刺激的巨噬细胞中 NF-κB 的激活。这些发现表明,橙皮苷对上皮屏障功能具有保护作用,此外还能减少 ROS 产生并减轻与牙周病相关的炎症反应。

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