Carnosic acid alleviates chronic alcoholic liver injury by regulating the SIRT1/ChREBP and SIRT1/p66shc pathways in rats.

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. 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. 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.

Gao L ，Shan W ，Zeng W ，Hu Y ，Wang G ，Tian X ，Zhang N ，Shi X ，Zhao Y ，Ding C ，Zhang F ，Liu K ，Yao J ... -  《-》

Salvianolic acid B protects against chronic alcoholic liver injury via SIRT1-mediated inhibition of CRP and ChREBP in rats.

Salvianolic acid B (SalB), a water-soluble polyphenol extracted from Radix Salvia miltiorrhiza, has been reported to possess many pharmacological activities. This study investigated the hepatoprotective effects of SalB in chronic alcoholic liver disease (ALD) and explored the related signaling mechanisms. In vivo, SalB treatment significantly attenuated ethanol-induced liver injury by blocking the elevation of serum aminotransferase activities and markedly decreased hepatic lipid accumulation by reducing serum and liver triglyceride (TG) and total cholesterol (TC) levels. Moreover, SalB treatment ameliorated ethanol-induced hepatic inflammation by decreasing the levels of hepatotoxic cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Importantly, SalB pretreatment significantly increased the expression of SIRT1 and downregulated the expression of inflammatory mediator C-reactive protein (CRP) and lipoprotein carbohydrate response element-binding protein (ChREBP). In vitro, SalB significantly reversed ethanol-induced down-regulation of SIRT1 and increased CRP and ChREBP expression. Interestingly, the effects of SalB on SIRT1, CRP and ChREBP were mostly abolished by treatment with either SIRT1 siRNA or EX527, a specific inhibitor of SIRT1, indicating that SalB decreased CRP and ChREBP expression by activating SIRT1. SalB exerted anti-steatotic and anti-inflammatory effects against alcoholic liver injury by inducing SIRT1-mediated inhibition of CRP and ChREBP expression.

Zhang N ，Hu Y ，Ding C ，Zeng W ，Shan W ，Fan H ，Zhao Y ，Shi X ，Gao L ，Xu T ，Wang R ，Gao D ，Yao J ... -  《-》

Carnosic acid attenuates acute ethanol-induced liver injury via a SIRT1/p66Shc-mediated mitochondrial pathway.

Tian X ，Hu Y ，Li M ，Xia K ，Yin J ，Chen J ，Liu Z ... -  《-》

Activation of the SIRT1/p66shc antiapoptosis pathway via carnosic acid-induced inhibition of miR-34a protects rats against nonalcoholic fatty liver disease.

Shan W ，Gao L ，Zeng W ，Hu Y ，Wang G ，Li M ，Zhou J ，Ma X ，Tian X ，Yao J ... -  《Cell Death & Disease》

Sirtuin 1-mediated inhibition of p66shc expression alleviates liver ischemia/reperfusion injury.

Yan H ，Jihong Y ，Feng Z ，Xiaomei X ，Xiaohan Z ，Guangzhi W ，Zhenhai M ，Dongyan G ，Xiaochi M ，Qing F ，Kexin L ，Xiaofeng T ... -  《-》