title: Glycycoumarin inhibits hepatocyte lipoapoptosis through activation of autophagy and inhibition of ER stress/GSK-3-mediated mitochondrial pathway.
abstract: Herbal medicine as an alternative approach in the treatment of disease has drawn growing attention. Identification of the active ingredient is needed for effective utilization of the herbal medicine. Licorice is a popular herbal plant that is widely used to treat various diseases including liver diseases. Glycycoumarin (GCM) is a representative of courmarin compounds isolated from licorice. In the present study, the protective effect of GCM on hepatocyte lipoapoptosis has been evaluated using both cell culture model of palmitate-induced lipoapoptosis and animal model of non-alcoholic steatohepatitis (NASH). The results demonstrated for the first time that GCM was highly effective in suppressing hepatocyte lipoapoptosis in both in vitro and in vivo. Mechanistically, GCM was able to re-activate the impaired autophagy by lipid metabolic disorders. In line with the activation of autophagy, ER stress-mediated JNK and mitochondrial apoptotic pathway activation was inhibited by GCM both in vitro and in vivo. In addition, inactivation of GSK-3 might also contribute to the protective effect of GCM on hepatocyte lipoapoptosis. Our findings supported GCM as a novel active component of licorice against non-alcoholic fatty liver disease (NAFLD).
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, National Engineering Research Center for Fruit and Vegetable Processing, Beijing, China No. 17 Qinghua East Road, Haidian District, Beijing, 100083, China.
authors.forename: Enxiang
authors.initials: E
authors.lastname: Zhang
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, National Engineering Research Center for Fruit and Vegetable Processing, Beijing, China No. 17 Qinghua East Road, Haidian District, Beijing, 100083, China.
authors.forename: Shutao
authors.initials: S
authors.lastname: Yin
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, National Engineering Research Center for Fruit and Vegetable Processing, Beijing, China No. 17 Qinghua East Road, Haidian District, Beijing, 100083, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Song
authors.affiliation: College of Veterinary Medicine, China Agricultural University, No. 2 Yunamingyuan West Road, Haidian District, Beijing, 100193, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Fan
authors.affiliation: Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, National Engineering Research Center for Fruit and Vegetable Processing, Beijing, China No. 17 Qinghua East Road, Haidian District, Beijing, 100083, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Hu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D003374:Coumarins / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006035:Glycyrrhiza / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D003374:Coumarins; C515155:glycycoumarin; D038362:Glycogen Synthase Kinase 3