Premium
Carnosic acid alleviates chronic alcoholic liver injury by regulating the SIRT1/ChREBP and SIRT1/p66shc pathways in rats
Author(s) -
Gao Lili,
Shan Wen,
Zeng Wenjing,
Hu Yan,
Wang Guangzhi,
Tian Xiaofeng,
Zhang Ning,
Shi Xue,
Zhao Yan,
Ding Chunchun,
Zhang Feng,
Liu Kexin,
Yao Jihong
Publication year - 2016
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201500878
Subject(s) - carnosic acid , carbohydrate responsive element binding protein , chemistry , alcoholic liver disease , oxidative stress , liver injury , apoptosis , downregulation and upregulation , programmed cell death , inflammation , endocrinology , pyroptosis , steatosis , medicine , biochemistry , antioxidant , transcription factor , cirrhosis , gene
Scope Carnosic acid (CA), which is extracted from rosemary, displays multiple pharmacological activities. This study aimed to investigate the effects of CA on chronic alcoholic liver injury and to elucidate the related mechanisms. Methods and results An in vivo rat model was established by feeding rats a liquid diet containing ethanol, and an in vitro model was created by treating HepG2 cells with 100 mM ethanol for 48 h. In the rat model of alcohol‐induced liver injury, CA significantly decreased serum aminotransferase, triglyceride and total cholesterol levels. Additionally, CA inhibited oxidative stress, inflammation, and cell death. Interestingly, CA activated SIRT1, which was associated with the downregulation of lipoprotein carbohydrate response element‐binding protein (ChREBP) and growth factor adapter protein (p66shc). In HepG2 cells, ethanol‐induced cell injury was associated with decreased SIRT1 and increased ChREBP and p66shc protein expression. These changes were reversed by CA but enhanced by a specific SIRT1 inhibitor, EX527. Moreover, the effects of CA on SIRT1, ChREBP, and p66shc were abolished by SIRT1 siRNA or EX527, indicating that CA decreased ChREBP and p66shc expression via SIRT1 activation. Conclusion CA exerted protective effects against alcoholic liver injury by activating the SIRT1/ChREBP and SIRT1/p66shc pathways, which are related to the anti‐steatosis, anti‐oxidant, and anti‐apoptosis effects.