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Asperosaponin VI protects alcohol-induced hepatic steatosis and injury via regulating lipid metabolism and ER stress

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机构: [1]School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, 510515, China [2]The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510400, China [3]School of Pharmacy, Guangzhou Xinhua University, Guangzhou, 510520, China [4]School of Pharmacy, Macau University of Science and Technology, Taipa, Macau [5]School of Pharmacy, Fudan University, Shanghai, 201203, China
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关键词: AFLD Asperosaponin VI Lipid metabolism AMPK ER stress

摘要:
Asperosaponin VI (AVI) is a natural triterpenoid saponin isolated from Dipsacus asper Wall with documented anti-inflammatory and bone protective effects. Our previous work reported that AVI protects the liver of septic mice from acute inflammatory damage. In this paper, we further explored the protective effect and the potential mechanisms of AVI in alcoholic fatty liver disease (AFLD).The Lieber-Decarli model was constructed to evaluate the effect of AVI on AFLD in C57BL/6 J mice. Additional in vitro work was performed to investigate HepG2 cells exposed to alcohol, then analyzed the degree of liver injury by detecting the ALT and AST levels both in the liver and serum. H&E staining and Sirius red staining were used to evaluate the histopathology variations in the liver. Further, observe lipid droplets in the cytoplasm by Oil Red O staining. We detected the expression of inflammatory cytokines with qualitative PCR; ROS, MDA, SOD, and GSH-px levels were analyzed to observe oxidative stress. Finally, exploring the activation of AMPK signaling pathway by real-time PCR and Western blotting.Histological examination of liver tissue combined with serum ALT and AST levels showed a significant protective effect of AVI against alcoholic liver injury in AFLD mice. Compared with the model group, AVI evidently improved antioxidant capacity, reduced inflammatory response and lipid accumulation both in vitro and in vivo. For mechanically, it was found that AVI up-regulated phosphorylation level of AMP-activated protein kinase (AMPK) and inhibited the endoplasmic reticulum stress (ER) pathway in AFLD.AVI protects mice from alcohol-induced hepatic steatosis and liver injury through activating AMPK signaling and repress ER stress, suggesting that it might be a potential therapeutic agent for AFLD.Copyright © 2023 Elsevier GmbH. All rights reserved.

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出版当年[2022]版:
大类 | 1 区 医学
小类 | 1 区 药物化学 1 区 药学 1 区 全科医学与补充医学 1 区 植物科学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 药物化学 1 区 全科医学与补充医学 1 区 药学 1 区 植物科学
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第一作者机构: [1]School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of Shock and Microcirculation, Southern Medical University, Guangzhou, 510515, China
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