title: Ligustrazine prevents alcohol-induced liver injury by attenuating hepatic steatosis and oxidative stress.
abstract: Alcoholic liver disease (ALD) is a major etiology of liver diseases, causing heavy health burdens personally and socially. Ligustrazine has been widely used in China due to its extensive pharmacological activities. However, the role of ligustrazine in ALD treatment remains unclear. Thus, this study is aimed to make up this gap and further uncover the potential mechanisms. The present work demonstrated that compared with the alcohol feeding group, ligustrazine-treated groups showed a clear decrease in aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities in serum, and a great improvement in liver histology. Additionally, ligustrazine reduced the number of foci containing CD45 positive cells and the expression of proteins associated with hepatic inflammation, apoptosis, and fibrosis. Further, ligustrazine obviously abolished alcohol-induced hepatic steatosis and hyperlipidemia. In addition, ligustrazine reversed alcohol-induced overexpression of sterol regulatory element-binding protein-1c and fatty acid synthase, and inhibition of peroxisome proliferator-activated receptor-alpha and carnitine palmitoyltransferase 1 in liver. Ligustrazine also ameliorated alcohol-induced increases in reactive oxygen species and malondialdehyde levels, and decreases in glutathione, superoxide dismutase, catalase, and glutathione reductase content in liver. Finally, chronic alcohol feeding inhibited the hepatic expression of nuclear factor erythroid 2-related factor 2 (Nrf2) at both mRNA and protein levels. Ligustrazine promoted Nrf2 expression and nuclear translocation in a dose-dependent manner. Collectively, for the first time, the present study demonstrated that ligustrazine remarkably improved chronic alcohol-induced liver injury by attenuating hepatic steatosis and oxidative stress. Further, Nrf2 activation might be requisite for ligustrazine to exert its protective effects.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China. Electronic address: yifeng2008love@163.com.
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China.
authors.forename: Wenxuan
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China.
authors.forename: Lianyun
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China.
authors.forename: Jiangjuan
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210023, China. Electronic address: nytws@163.com.
authors.forename: Shizhong
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D005234:Fatty Liver / Q000139:chemically induced* / Q000517:prevention & control; D008108:Liver Diseases, Alcoholic / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011719:Pyrazines; C017953:tetramethylpyrazine
keywords: Alcoholic liver disease; Hepatic steatosis; Ligustrazine; Liver injury; Nuclear factor erythroid 2-related factor 2; Oxidative stress