机构：[1]General Surgery Center of PLA, the General Hospital of Western Theater Command, Chengdu 610083, China[2]Department of Pharmacy, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China四川省人民医院[3]Central Laboratory, the General Hospital of Western Theater Command, Chengdu 610083, China[4]Department of Ultrasound, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, Chengdu 610041, China四川省肿瘤医院[5]Department of Pharmacy, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China四川省人民医院
Green tea has been considered as a health-promoting beverage and is widely consumed worldwide. Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol derived from green tea leaves with potent antioxidative and chemopreventive activities, has been reported to offer protection against inflammation-driven tissue damage. Here, we evaluated the protective effects of EGCG against lung injury during acute pancreatitis (AP) and further revealed the detailed mechanism. The results showed that EGCG significantly attenuated l-arginine-induced AP and the consequent pulmonary damage in mice. Moreover, EGCG substantially attenuated oxidative stress and concurrently suppressed NOD-like receptor protein 3 (NLRP3) inflammasome activation in the lung. In vitro, EGCG considerably reduced the production of mitochondrial reactive oxygen species (mtROS) and oxidized mitochondrial DNA (ox-mtDNA) in alveolar macrophages (AMs) challenged with AP-conditioned plasma. Meanwhile, the amount of ox-mtDNA bound to NLRP3 decreased significantly by the treatment with EGCG, resulting in impaired NLRP3 inflammasome activation. In addition, the antagonism of NLRP3 signaling by EGCG was affected in the presence of the mtROS stimulant rotenone or scavenger Mito-TEMPO. Altogether, EGCG possesses potent activity to attenuate lung injury during AP progression by inhibiting NLRP3 inflammasome activation. As for the mechanism, the EGCG-conferred restriction of NLRP3 inflammasome activation probably arises from the elimination of mtROS as well as its oxidative product ox-mtDNA, which consequently enables the protection against AP-associated lung injury.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81570582, 81772001]; Sichuan Province Science and Technology Project [2020YFSY0022]
第一作者机构：[1]General Surgery Center of PLA, the General Hospital of Western Theater Command, Chengdu 610083, China[2]Department of Pharmacy, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China
共同第一作者：
通讯作者：
通讯机构：[2]Department of Pharmacy, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, China[5]Department of Pharmacy, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China
推荐引用方式(GB/T 7714)：
Luo Zhu-Lin,Sun Hong-Yu,Wu Xiao-Bo,et al.Epigallocatechin-3-gallate attenuates acute pancreatitis induced lung injury by targeting mitochondrial reactive oxygen species triggered NLRP3 inflammasome activation[J].FOOD & FUNCTION.2021,12(12):5658-5667.doi:10.1039/d1fo01154e.
农林科学