title: Treatment of rats with Jiangzhi Capsule improves liquid fructose-induced fatty liver: modulation of hepatic expression of SREBP-1c and DGAT-2.
abstract: BACKGROUND
  Jiangzhi Capsule is an Australian listed patented traditional Chinese medicine and has been used for management of lipid abnormalities over the past 10 years. To obtain a better understanding regarding Jiangzhi Capsule, the present study investigated the effects and underlying mechanisms of Jiangzhi Capsule on chronic fructose overconsumption-induced lipid abnormalities.
  
  
  METHODS
  Male rats were treated with liquid fructose in their drinking water over 14 weeks. Jiangzhi Capsule was co-administered (once daily, by oral gavage) during the last 7 weeks. Indexes of lipid and glucose homeostasis were determined enzymatically, by ELISA and/or histologically. Gene expression was analyzed by real-time PCR, Western blot and/or immunohistochemistry.
  
  
  RESULTS
  Treatment with Jiangzhi Capsule (100 mg/kg) attenuated fructose-induced excessive triglyceride accumulation and Oil Red O-stained area in the liver. This effect was accompanied by amelioration of hyperinsulinemia. There was no significant difference in intakes of fructose and chow, and body weight between fructose control and fructose Jiangzhi Capsule-treated groups. Mechanistically, Jiangzhi Capsule downregulated fructose-stimulated hepatic overexpression of sterol regulatory element binding protein (SREBP)-1/1c at the mRNA and protein levels. Accordingly, the SREBP-1c downstream genes, acetyl-CoA carboxylase-1 and stearoyl-CoA desaturase-1, were also inhibited. In addition, acyl-coenzyme A:diacylglycerol acyltransferase (DGAT)-2 expression at the mRNA and protein levels in the liver was also inhibited after Jiangzhi Capsule treatment. In contrast, Jiangzhi Capsule affected neither carbohydrate response element binding protein, peroxisome proliferator-activated receptor (PPAR)-gamma and DGAT-1, nor PPAR-alpha and its target genes.
  
  
  CONCLUSIONS
  These findings demonstrate the anti-steatotic action of Jiangzhi Capsule in fructose-fed rats, and modulation of hepatic SREBP-1c and DGAT-2 involved in hepatic de novo synthesis of fatty acids and triglyceride, respectively. Our findings provide an evidence-based and mechanistic understanding of Jiangzhi Capsule supporting its application for the prevention and/or treatment of fatty liver and its associated disorders in clinical practice.
authors.affiliation: Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing, China. zhaoy2014@outlook.com.
authors.forename: Yuanyang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: The Laboratory Animal Center, Chongqing Medical University, Chongqing, China. cypyq@126.com.
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW, Australia. yifanyang@sitcm.edu.au.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Central Clinical School, Royal Prince Alfred Hospital, The University of Sydney, Sydney, NSW, Australia. robert.batey@uni.sydney.edu.au.
authors.forename: Robert
authors.initials: R
authors.lastname: Batey
authors.affiliation: Laboratory of Traditional Chinese Medicine, Chongqing Medical University, Chongqing, China. wjwcq68@163.com.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Endocrinology and Metabolism Group, Sydney Institute of Health Sciences/Sydney Institute of Traditional Chinese Medicine, Sydney, NSW, Australia. yuhao@sitcm.edu.au.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D051048:Diacylglycerol O-Acyltransferase / Q000235:genetics* / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005234:Fatty Liver / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy* / Q000235:genetics; D005632:Fructose; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020218:Response Elements / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics* / Q000378:metabolism
chemical_list: D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; C000597921:jiangzhi; D005632:Fructose; C522579:Dgat2 protein, rat; D051048:Diacylglycerol O-Acyltransferase