Xu Tianle, Liu Run, Zhu Hao, Zhou Yu, Pei Tianxu, Yang Zhangping
Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou University, Yangzhou 225009, China.
College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.
Antioxidants (Basel). 2022 May 6;11(5):914. doi: 10.3390/antiox11050914.
This study aimed to evaluate whether (-)-epigallocatechin-3-gallate (EGCG) alleviates hepatic responses to lipopolysaccharide (LPS)-induced inflammation and oxidation. Isolated bovine hepatocytes and BALB/c mice were used for LPS challenge and EGCG pretreatment experiments in vitro and in vivo. LPS-challenged (6 μg/mL) hepatocytes exhibited increased levels of NF-κB (p65 and IκBα) and MAPK (38, ERK, JNK) phosphorylation as well as increased binding activity of p65 to target pro-inflammatory gene promoters, and these effects were suppressed by pretreatment with 50 μM EGCG. Moreover, the reduction in Nrf2 signaling and antioxidant enzyme activities induced by LPS stimulation were reversed upon EGCG treatment. In vivo experiments demonstrated the protective role of EGCG in response to GalN/LPS-induced mortality and oxidative damage. Together, our results suggest that EGCG is hepatoprotective via inhibition of MAPK/NF-κB signaling and activation of the Nrf2 cascade. This information might help design strategies for counteracting hepatitis in ruminants and monogastric animals.
本研究旨在评估（-）-表没食子儿茶素-3-没食子酸酯（EGCG）是否能减轻肝脏对脂多糖（LPS）诱导的炎症和氧化反应。分离的牛肝细胞和BALB/c小鼠用于体外和体内的LPS刺激及EGCG预处理实验。受到LPS刺激（6μg/mL）的肝细胞表现出NF-κB（p65和IκBα）和MAPK（p38、ERK、JNK）磷酸化水平升高，以及p65与靶促炎基因启动子的结合活性增加，而50μM EGCG预处理可抑制这些效应。此外，EGCG处理可逆转LPS刺激诱导的Nrf2信号通路和抗氧化酶活性降低。体内实验证明了EGCG对GalN/LPS诱导的死亡和氧化损伤具有保护作用。总之，我们的结果表明，EGCG通过抑制MAPK/NF-κB信号通路和激活Nrf2级联反应发挥肝脏保护作用。这一信息可能有助于设计对抗反刍动物和单胃动物肝炎的策略。
