提取物减轻实验性牙周炎中的氧化应激和炎症。

Extract Attenuates Oxidative Stress and Inflammation in Experimental Periodontitis.

作者信息

Yuan Lin, Kong Chenfei, Shi Naixu, Chen Jiapeng, Zhang Tianfu, Wang Xiaofeng

机构信息

Department of Stomatology, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China.

Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China.

出版信息

J Inflamm Res. 2025 Jun 23;18:8263-8276. doi: 10.2147/JIR.S522383. eCollection 2025.

DOI:10.2147/JIR.S522383

PMID:40585044

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12204106/

Abstract

BACKGROUND

is a traditional Chinese herbal medicine with anti-inflammatory, analgesic and antibacterial effects. However, its role in the treatment of Periodontal disease has not been elaborated in detail.

PURPOSE

This study aimed to elucidate the dual-target anti-inflammatory and antioxidant mechanisms of extract (HME) in periodontitis treatment, focusing on its modulation of the Nrf2/NF-κB crosstalk.

METHODS

The periodontitis animal model of SD rats was established by ligation combined with Porphyromonas gingivalis (Pg) stimulation. The rats were locally administered HME (0.25%, 0.5%, and 1%, 0.5 mL/twice/day) for 14 days. Inflammatory responses of alveolar bone, expression of osteogenic related biomarkers, and activation of Nrf2/NF-κB signaling pathway were detected. In addition, LPS induced human periodontal ligament cells (HPDLs) to measure the effect of HME on cell viability, inflammatory response, Nrf2/NF- κB pathway and oxidative stress.

RESULTS

HME administration demonstrated significant efficacy in a ligature-induced periodontitis rat model: serum pro-inflammatory cytokines (IL-1β, IL-2, IL-6, IL-18, GM-CSF, and ICAM1) decreased by 24.9-50.6% at high HME concentrations, while Th2-related factors IL-4/IL-13 returned to baseline levels. Histopathological analysis revealed that HME maintained gingival epithelial integrity and suppressed osteoclast activity in a dose-dependent manner by downregulating RANKL. Mechanistic studies indicated that HME attenuated NF-κB activation by reducing nuclear p65 protein (44.1%) and enhanced the Nrf2-mediated antioxidant response, normalizing oxidative stress markers (MDA decreased by 55.3%; SOD restored to 142.3 U/mg). In vitro experiments confirmed HME's cytocompatibility at concentrations below 200µg/mL and its resistance to LPS stimulation, reducing ROS overaccumulation by 16.46% through modulation of the Nrf2/NF-κB axis.

CONCLUSION

HME inhibits the progression of periodontitis in rats by downregulating the expression of inflammatory factors, alleviating oxidative stress, and repairing the Nrf2/NF-κB signaling pathway.

摘要

背景

是一种具有抗炎、镇痛和抗菌作用的传统中草药。然而，其在牙周疾病治疗中的作用尚未得到详细阐述。

目的

本研究旨在阐明提取物（HME）在牙周炎治疗中的双靶点抗炎和抗氧化机制，重点关注其对Nrf2/NF-κB相互作用的调节。

方法

通过结扎联合牙龈卟啉单胞菌（Pg）刺激建立SD大鼠牙周炎动物模型。大鼠局部给予HME（0.25%、0.5%和1%，0.5 mL/每日两次），持续14天。检测牙槽骨的炎症反应、成骨相关生物标志物的表达以及Nrf2/NF-κB信号通路的激活情况。此外，用脂多糖诱导人牙周膜细胞（HPDLs），以测定HME对细胞活力、炎症反应、Nrf2/NF-κB通路和氧化应激的影响。

结果

在结扎诱导的牙周炎大鼠模型中，给予HME显示出显著疗效：高浓度HME时，血清促炎细胞因子（IL-1β、IL-2、IL-6、IL-18、GM-CSF和ICAM1）降低了24.9 - 50.6%，而Th2相关因子IL-4/IL-13恢复到基线水平。组织病理学分析显示，HME通过下调RANKL以剂量依赖性方式维持牙龈上皮完整性并抑制破骨细胞活性。机制研究表明，HME通过减少核p65蛋白（44.1%）减弱NF-κB激活，并增强Nrf2介导的抗氧化反应，使氧化应激标志物正常化（MDA降低55.3%；SOD恢复到142.3 U/mg）。体外实验证实HME在浓度低于200µg/mL时具有细胞相容性，并对脂多糖刺激具有抗性，通过调节Nrf2/NF-κB轴使ROS过度积累减少16.46%。