title: Chlorpromazine-induced perturbations of bile acids and free fatty acids in cholestatic liver injury prevented by the Chinese herbal compound Yin-Chen-Hao-Tang.
abstract: BACKGROUND
  Yin-Chen-Hao-Tang (YCHT), a commonly used as a traditional chinese medicine for liver disease. Several studies indicated that YCHT may improving hepatic triglyceride metabolism and anti-apoptotic response as well as decreasing oxidative stress .However, little is known about the role of YCHT in chlorpromazine (CPZ) -induced chlolestatic liver injury. Therefore, we aimed to facilitate the understanding of the pathogenesis of cholestatic liver injury and evaluate the effect of Yin-Chen-Hao-Tang (YCHT) on chlorpromazine (CPZ)-induced cholestatic liver injury in rats based on the change of bile acids (BAs) and free fatty acids (FFAs) alone with the biochemical indicators and histological examination.
  
  
  METHODS
  We conducted an experiment on CPZ-induced cholestatic liver injury in Wistar rats with and without YCHT for nine consecutive days. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), total bilirubin (TBIL), total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C) were measured to evaluate the protective effect of YCHT against chlorpromazine (CPZ)-induced cholestatic liver injury. Histopathology of the liver tissue showed that pathological injuries were relieved after YCHT pretreatment. In addition, ultra-performance lipid chromatography coupled with quadrupole mass spectrometry (UPLC-MS) and gas chromatography coupled with mass spectrometry (GC-MS) was applied to determine the content of bile acids, free fatty acids, respectively.
  
  
  RESULTS
  Obtained data showed that YCHT attenuated the effect of CPZ-induced cholestatic liver injury, which was manifested by the serum biochemical parameters and histopathology of the liver tissue. YCHT regulated the lipid levels as indicated by the reversed serum levels of TC, TG, and LDL-C. YCHT also regulated the disorder of BA and FFA metabolism by CPZ induction.
  
  
  CONCLUSIONS
  Results indicated that YCHT exerted a protective effect on CPZ-induced cholestasis liver injury. The variance of BA and FFA concentrations can be used to evaluate the cholestatic liver injury caused by CPZ and the hepatoprotective effect of YCHT.
authors.affiliation: The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the State Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 201210, Shanghai, China. cherish0814@126.com.
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Yang
authors.affiliation: The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the State Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 201210, Shanghai, China. fanyangforever@gmail.com.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the State Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 201210, Shanghai, China. shs912vv@126.com.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Tang
authors.affiliation: The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the State Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 201210, Shanghai, China. nail8219@126.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Ding
authors.affiliation: The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the State Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 201210, Shanghai, China. skyxu_1983@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the State Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 201210, Shanghai, China. xiongyhfriend@hotmail.com.
authors.forename: Yinhua
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the State Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 201210, Shanghai, China. wangzht@hotmail.com.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: The Ministry of Education Key Laboratory for Standardization of Chinese Medicines and the State Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 201210, Shanghai, China. yangli7951@hotmail.com.|Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. yangli7951@hotmail.com.|Institute of Traditional Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201210, China. yangli7951@hotmail.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D019306:Artemisia; D001647:Bile Acids and Salts / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000517:prevention & control*; D002746:Chlorpromazine / Q000009:adverse effects*; D002779:Cholestasis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D032062:Gardenia; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D008516:Medicine, Chinese Traditional; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D051381:Rats; D017208:Rats, Wistar; D012250:Rheum
chemical_list: D001647:Bile Acids and Salts; D004365:Drugs, Chinese Herbal; D005230:Fatty Acids, Nonesterified; C542425:yin-chen-hao-tang; D002746:Chlorpromazine