(-)-表没食子儿茶素没食子酸酯通过 ROS 介导的 MAPK 和 NF-κB 通路抑制香烟烟雾诱导的人心肌细胞炎症。

(-)-Epigallocatechin-3-gallate suppresses cigarette smoke-induced inflammation in human cardiomyocytes via ROS-mediated MAPK and NF-κB pathways.

机构信息

Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong.

Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong; Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong.

出版信息

Phytomedicine. 2019 May;58:152768. doi: 10.1016/j.phymed.2018.11.028. Epub 2018 Nov 20.

Abstract

BACKGROUND

Cigarette smoking is the leading cause for the initiation and development of cardiovascular disease (CVD). Oxidative stress and inflammatory responses play important roles in the pathophysiological processes of smoking-induced cardiac injury. (-)-epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, which is made from Camellia sinensis leaves, has been reported to possess potent anti-oxidant property.

PURPOSE

This study aims to investigate whether the antioxidant EGCG could alleviate cigarette smoke medium (CSM)-induced inflammation in human AC16 cardiomyocytes in vitro.

METHODS

Human AC16 cardiomyocytes were pre-treated with EGCG, N-acetyl-L-cysteine (NAC), or specific inhibitors for 30 min before 4% CSM was added. Supernatant was collected for determination of interleukin (IL)-8 by ELISA and cells were collected for flow cytometry, biochemical assays and Western blot analysis.

RESULTS

EGCG treatment significantly attenuated CSM-induced oxidative stress as evidenced by reducing intracellular and mitochondrial reactive oxygen species (ROS) generations and preventing antioxidant depletion. EGCG treatment reduced CSM-induced inflammatory chemokine interleukin (IL)-8 productions in the supernatant via the inhibition of ERK1/2, p38 MAPK and NF-κB pathways. EGCG treatment further inhibited CSM-induced cell apoptosis.

CONCLUSION

Taken together, EGCG protected against CSM-induced inflammation and cell apoptosis by attenuating oxidative stress via inhibiting ERK1/2, p38 MAPK, and NF-κB activation in AC16 cardiomyocytes. These findings suggest that EGCG with its antioxidant, anti-inflammatory and anti-apoptotic properties may act as a promising cardioprotective agent against ROS-mediated cardiac injury.

摘要

背景

吸烟是引发和导致心血管疾病(CVD)的主要原因。氧化应激和炎症反应在吸烟引起的心脏损伤的病理生理过程中起着重要作用。(-)-表没食子儿茶素-3-没食子酸酯(EGCG)是绿茶中含量最丰富的儿茶素,来源于茶叶,已被报道具有很强的抗氧化特性。

目的

本研究旨在探讨抗氧化剂 EGCG 是否可以减轻体外人 AC16 心肌细胞中香烟烟雾介质(CSM)诱导的炎症。

方法

人 AC16 心肌细胞在用 EGCG、N-乙酰-L-半胱氨酸(NAC)或特定抑制剂预处理 30 分钟后,加入 4% CSM。收集上清液通过 ELISA 测定白细胞介素(IL)-8,收集细胞进行流式细胞术、生化测定和 Western blot 分析。

结果

EGCG 处理显著减轻 CSM 诱导的氧化应激,表现为减少细胞内和线粒体活性氧(ROS)的产生,并防止抗氧化剂耗竭。EGCG 处理通过抑制 ERK1/2、p38 MAPK 和 NF-κB 途径减少 CSM 诱导的上清液中炎症趋化因子白细胞介素(IL)-8 的产生。EGCG 处理进一步抑制 CSM 诱导的细胞凋亡。

结论

总之,EGCG 通过抑制 ERK1/2、p38 MAPK 和 NF-κB 的激活,减轻 AC16 心肌细胞中的氧化应激,从而防止 CSM 诱导的炎症和细胞凋亡。这些发现表明,EGCG 具有抗氧化、抗炎和抗凋亡特性,可能是一种有前途的针对 ROS 介导的心脏损伤的心脏保护剂。

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