title: Oxymatrine attenuates hepatic steatosis in non-alcoholic fatty liver disease rats fed with high fructose diet through inhibition of sterol regulatory element binding transcription factor 1 (Srebf1) and activation of peroxisome proliferator activated receptor alpha (Pparα).
abstract: The aim of this study was to examine the therapeutic effect of oxymatrine, a monomer isolated from the medicinal plant Sophora flavescens Ait, on the hepatic lipid metabolism in non-alcoholic fatty liver (NAFLD) rats and to explore the potential mechanism. Rats were fed with high fructose diet for 8 weeks to establish the NAFLD model, then were given oxymatrine treatment (40, 80, and 160 mg/kg, respectively) for another 8 weeks. Body weight gain, liver index, serum and liver lipids, and histopathological evaluation were measured. Enzymatic activity and gene expression of the key enzymes involved in the lipogenesis and fatty acid oxidation were assayed. The results showed that oxymatrine treatment reduced body weight gain, liver weight, liver index, dyslipidemia, and liver triglyceride level in a dose dependant manner. Importantly, the histopathological examination of liver confirmed that oxymatrine could decrease the liver lipid accumulation. The treatment also decreased the fatty acid synthase (FAS) enzymatic activity and increased the carnitine palmitoyltransferase 1A (CPT1A) enzymatic activity. Besides, oxymatrine treatment decreased the mRNA expression of sterol regulatory element binding transcription factor 1(Srebf1), fatty acid synthase (Fasn), and acetyl CoA carboxylase (Acc), and increased the mRNA expression of peroxisome proliferator activated receptor alpha (Pparα), carnitine palmitoyltransferase 1A (Cpt1a), and acyl CoA oxidase (Acox1) in high fructose diet induced NAFLD rats. These results suggested that the therapeutic effect of oxymatrine on the hepatic steatosis in high fructose diet induced fatty liver rats is partly due to down-regulating Srebf1 and up-regulating Pparα mediated metabolic pathways simultaneously.
authors.affiliation: Department of Endocrinology, The Third Hospital of Shijiazhuang City Affiliated to Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Li-juan
authors.initials: LJ
authors.lastname: Shi
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Guang-yao
authors.initials: GY
authors.lastname: Song
authors.forename: He-fang
authors.initials: HF
authors.lastname: Zhang
authors.forename: Zhi-juan
authors.initials: ZJ
authors.lastname: Hu
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Dong-hui
authors.initials: DH
authors.lastname: Zhang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004032:Diet / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy; D002149:Energy Intake / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005632:Fructose / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D010084:Oxidation-Reduction / Q000187:drug effects; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D011807:Quinolizines / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D051780:Sterol Regulatory Element Binding Protein 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000093842:Matrines
chemical_list: D000470:Alkaloids; D005227:Fatty Acids; D005632:Fructose; D047493:PPAR alpha; D011807:Quinolizines; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; C497389:Srebf1 protein, rat; C037573:oxymatrine; D000093842:Matrines
keywords: Fatty acid oxidation; Fatty acid synthesis; Liver steatosis; Oxymatrine