title: Carnosic acid protects non-alcoholic fatty liver-induced dopaminergic neuron injury in rats.
abstract: Non-alcoholic fatty liver disease (NAFLD) has been reported to induce cognitive impairments of hippocampus and may influence central nervous system. In the present study, we investigated whether carnosic acid (CA) ameliorates dopaminergic neuron injury in a rat model of NAFLD. In order to induce NAFLD, rats were fed with high-fat diet (HFD) for 10 weeks. We found that continued CA administration reduced lipid accumulation marked by decreases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels, and an increase in high-density lipoprotein cholesterol (HDL-C) level in the serum. H&E staining revealed that feeding CA reduced lipid droplets accumulation, and alleviated oxidative stress by increasing in superoxide dismutase (SOD) level and decreasing in malondialdehyde (MDA) level in the liver. In addition, by measuring several parameters of gait analysis, we demonstrated that CA treatment ameliorated behavioral impairments, as evidenced by decreased duration and maximum variation, accompanied by increased average speed and cadence. Furthermore, CA treated-animals displayed an increase in the contents of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacelic acid (DOPAC) and elevated the expressions of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) as well as the TH protein in the striatum. Together, these findings suggest that CA may be an effective agent in protecting rats from NAFLD-induced dopaminergic neuron injury.
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, People's Republic of China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, People's Republic of China. zhoujun_2005@163.com.
authors.forename: Junjun
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, People's Republic of China.|Department of Pharmacy, Second Affiliated Hospital of Dalian Medical University, Dalian, 116023, People's Republic of China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, People's Republic of China.
authors.forename: Chunchun
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, 116044, People's Republic of China. yaojihong65@hotmail.com.
authors.forename: Jihong
authors.initials: J
authors.lastname: Yao
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D045784:Abietanes / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology*; D007794:Lameness, Animal / Q000188:drug therapy; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D045784:Abietanes; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D020011:Protective Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D014446:Tyrosine 3-Monooxygenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C018381:salvin
keywords: Carnosic acid; Dopaminergic neuron injury; Non-alcoholic fatty liver disease