Ethanol Extract of Pinus koraiensis Leaf Ameliorates Alcoholic Fatty Liver via the Activation of LKB1–AMPK Signaling In Vitro and In Vivo

Abstract

Although Pinus koraiensis leaf (PKL) was reported for its anti-diabetes, anti-obesity and anticancer effects as a folk remedy, the inhibitory effect of PKL on alcoholic fatty liver has never been elucidated yet. This study investigated the molecular mechanisms of PKL on alcoholic fatty liver in HepG2 cells, Sprague Dawley (SD) rats and Imprinting Control Region (ICR) mice. Pinus koraiensis leaf increased phosphorylation of liver kinase B1 (LKB1)/AMP-activated protein kinase signaling, low-density lipoprotein receptor and decreased fatty acid biosynthesis-related proteins such as sterol regulatory element-binding protein 1c, fatty acid synthase, 3-hydroxy-3-methylglutaryl-CoA reductase in HepG2 cells. In SD rats with 25% alcohol-induced fatty liver, PKL suppressed the levels of aspartate aminotransferase and triglyceride and also enhanced the activities of antioxidant enzymes including superoxide dismutase, glutathione peroxidase and glutathione s-transferase compared with untreated control. Furthermore, PKL increased serum alcohol dehydrogenase and serum aldehyde dehydrogenase, but decreased serum alcohol concentration in ICR mice after alcohol administration. Consistently, histochemical analysis revealed that PKL attenuated alcohol-induced fatty liver in SD rats. Overall, these findings suggest that PKL ameliorates alcohol-induced fatty liver via activation of LKB1-AMP-activated protein kinase and modulation of proteins related to lipogenesis synthesis, cholesterol synthesis and fatty acid oxidation. Copyright © 2017 John Wiley & Sons, Ltd.

Myricitrin ameliorates ethanol-induced steatosis in mouse AML12 liver cells by activating AMPK, and reducing oxidative stress and expression of inflammatory cytokines

“…Furthermore, the effect of treatment with myricitrin on mRNA expression of SREBP-1c and FAS was determined. SREBP-1c and FAS genes are regulated by AMPK and control the synthesis of fatty acids in ethanol-stimulated liver cells (21,25,26). Treatment with 100 mM ethanol resulted in a significant increase in SREBP-1c mRNA expression levels compared with the control group and this increase was significantly attenuated following treatment of ethanol-stimulated cells with myricitrin (P<0.05; Fig.…”

Beneficial effects of Chinese herbs in the treatment of fatty liver diseases

“…3 A). 65 , 66 , 67 , 68 , 69 , 70 , 71 Allicin, the compound found in fresh garlic blends, improves alcohol dehydrogenase activity in AFLD mice. Most of the Chinese herbs that exhibit an attenuation effect on AFLD act as anti-oxidative or anti-inflammatory agents.…”

The underlying hepatoprotective mechanism of PKC#963 in alcohol or carbon tetrachloride induced liver injury via inhibition of iNOS, COX‐2, and p‐STAT3 and enhancement of SOD and catalase

“…Since some natural products are known to protect against liver injury (Xiong & Guan, 2017), combination therapy with natural products is attractive with a low dose of natural products (Watkins, Wu, Zhang, Davis, & Xu, 2015) to maximize efficacy and reduce side effects (Del Prete et al, 2012; Gilani & Rahman, 2005; Sauter, 2020; Singh, Cho, & Upadhyay, 2015; Zhang, Wang, Jia, & Kong, 2018). Pinus koraiensis leaves are reported to have anti‐obesity (Lee et al, 2016), anticancer (Ahn et al, 2018), anti‐fatty liver and antioxidant effects (Hong et al, 2017), while S. chinensis is known to have anticancer (Alaklabi, Arif, Ahamed, Surendra Kumar, & Idhayadhulla, 2018), and antioxidant effects (Kim et al, 2014). Also, Lycium barbarum has anticancer (D. S. Xu, Kong, & Ma, 1996) and antioxidant activities (W. Xu et al, 2018).…”