title: 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.
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Sang-Hyuk
authors.initials: SH
authors.lastname: Hong
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Lee
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Bonglee
authors.identifier: http://orcid.org/0000-0002-8678-156X
authors.initials: B
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Min-Ho
authors.initials: MH
authors.lastname: Nam
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Bum-Sang
authors.initials: BS
authors.lastname: Shim
authors.affiliation: College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Korea.
authors.forename: Sung-Hoon
authors.identifier: http://orcid.org/0000-0003-2423-1973
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000737:chemistry / Q000633:toxicity*; D005235:Fatty Liver, Alcoholic; D005982:Glutathione Transferase / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D010766:Phosphorylation; D028223:Pinus / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018515:Plant Leaves / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D010936:Plant Extracts; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D000431:Ethanol; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; C488755:Stk11 protein, rat; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMP-activated protein kinase; Pinus koraiensis leaf; alcohol dehydrogenase; alcoholic fatty liver; aldehyde dehydrogenase