title: Sweroside ameliorates α-naphthylisothiocyanate-induced cholestatic liver injury in mice by regulating bile acids and suppressing pro-inflammatory responses.
abstract: OBJECTIVE
  Sweroside is an iridoid glycoside with diverse biological activities. In the present study we investigated the effects of sweroside on α-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury in mice.
  
  
  METHODS
  Mice received sweroside (120 mg·kg(-1)·d(-1), ig) or a positive control INT-747 (12 mg·kg(-1)·d(-1), ig) for 5 d, and ANIT (75 mg/kg, ig) was administered on d 3. The mice were euthanized on d 5, and serum biochemical markers, hepatic bile acids and histological changes were analyzed. Hepatic expression of genes related to pro-inflammatory mediators and bile acid metabolism was also assessed. Primary mouse hepatocytes were exposed to a reconstituted mixture of hepatic bile acids, which were markedly elevated in the ANIT-treated mice, and the cell viability and expression of genes related to pro-inflammatory mediators were examined.
  
  
  RESULTS
  Administration of sweroside or INT-747 effectively ameliorated ANIT-induced cholestatic liver injury in mice, as evidenced by significantly reduced serum biochemical markers and attenuated pathological changes in liver tissues. Furthermore, administration of sweroside or INT-747 significantly decreased ANIT-induced elevation of individual hepatic bile acids, such as β-MCA, CA, and TCA, which were related to its effects on the expression of genes responsible for bile acid synthesis and transport as well as pro-inflammatory responses. Treatment of mouse hepatocytes with the reconstituted bile acid mixture induced significant pro-inflammatory responses without affecting the cell viability.
  
  
  CONCLUSIONS
  Sweroside attenuates ANIT-induced cholestatic liver injury in mice by restoring bile acid synthesis and transport to their normal levels, as well as suppressing pro-inflammatory responses.
authors: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines and the State Administration of Traditional Chinese Medicine (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Qiao-Ling
authors: QL
authors: Yang
authors: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines and the State Administration of Traditional Chinese Medicine (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Fan
authors: F
authors: Yang
authors: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines and the State Administration of Traditional Chinese Medicine (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Jun-Ting
authors: JT
authors: Gong
authors: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines and the State Administration of Traditional Chinese Medicine (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Xiao-Wen
authors: XW
authors: Tang
authors: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines and the State Administration of Traditional Chinese Medicine (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Guang-Yun
authors: GY
authors: Wang
authors: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines and the State Administration of Traditional Chinese Medicine (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Zheng-Tao
authors: ZT
authors: Wang
authors: The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines and the State Administration of Traditional Chinese Medicine (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.|Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors: Li
authors: L
authors: Yang
mesh_terms: D015058:1-Naphthylisothiocyanate / Q000633:toxicity*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000494:pharmacology; D015415:Biomarkers / Q000097:blood; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002779:Cholestasis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000276:immunology; D007155:Immunologic Factors / Q000235:genetics; D057888:Iridoid Glucosides / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D061251:Primary Cell Culture
chemical_list: D000893:Anti-Inflammatory Agents; D001647:Bile Acids and Salts; D015415:Biomarkers; D007155:Immunologic Factors; D057888:Iridoid Glucosides; D015058:1-Naphthylisothiocyanate; C049412:sweroside