title: Protective effects of petroleum ether extracts of Herpetospermum caudigerum against α-naphthylisothiocyanate-induced acute cholestasis of rats.
abstract: BACKGROUND
  The ripe seeds of Herpetospermum caudigerum have been used in Tibetan folk medicine for treatment of bile or liver diseases including jaundice, hepatitis, intumescences or inflammation. Previously reports suggested that the seed oil and some lignans from H. caudigerum exhibited protective effects against carbon tetrachloride (CCl4)-induced hepatic damage in rats, which may be related to their free radical scavenging effect. However, the protective effect of H. caudigerum against cholestasis is still not revealed. The aim of the present study was to investigate the pharmacological effect and the chemical constituents of the petroleum ether extract (PEE) derived from H. caudigerum against α-naphthylisothiocyanate (ANIT)-induced acute cholestasis in rats.
  
  
  METHODS
  Male cholestatic Sprague-Dawley (SD) rats induced by ANIT (60mg/kg) were orally administered with PEE (350, 700 and 1400mg/kg). Levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-Glutamyl transpeptidase (γ-GTP), total bilirubin (TBIL), direct bilirubin (DBIL) and total bile acid (TBA), as well as bile flow, and histopathological assay were evaluated. Hepatic malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione S-transferase (GST), and nitric monoxide (NO) in liver were measured to explore the possible protective mechanisms. Phytochemical analysis of PEE was performed by gas chromatography-mass spectrometer (GC-MS).
  
  
  RESULTS
  PEE have exhibited significant and dose-dependent protective effect on ANIT-induced liver injury by reduce the increases in serum levels of ALT, AST, ALP, γ-GTP, TBIL, DBIL and TBA, restore the bile flow in cholestatic rats, and reduce the severity of the pathological tissue damage induced by ANIT. Hepatic MDA, MPO and NO contents in liver tissue were reduced, while SOD and GST activities were elevated in liver tissue. 49 compounds were detected and 39 of them were identified by GC-MS analysis, in which long-chain fatty acids were the main constituents.
  
  
  CONCLUSIONS
  PEE exhibited a dose-dependently protective effect on ANIT-induced liver injury in cholestatic rats with the potential mechanism of attenuated oxidative stress in the liver tissue, and the possible active compounds were long-chain fatty acids.
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), Southwest University, Chongqing 400715, PR China; TAAHC-SWU Medicinal Plant R&D Center, XiZang Agriculture and Animal Husbandry College, Nyingchi, Tibet 860000, PR China.
authors.forename: Wen-Rui
authors.initials: WR
authors.lastname: Cao
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), Southwest University, Chongqing 400715, PR China; TAAHC-SWU Medicinal Plant R&D Center, XiZang Agriculture and Animal Husbandry College, Nyingchi, Tibet 860000, PR China.
authors.forename: Jing-Qiu
authors.initials: JQ
authors.lastname: Ge
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), Southwest University, Chongqing 400715, PR China; TAAHC-SWU Medicinal Plant R&D Center, XiZang Agriculture and Animal Husbandry College, Nyingchi, Tibet 860000, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), Southwest University, Chongqing 400715, PR China; TAAHC-SWU Medicinal Plant R&D Center, XiZang Agriculture and Animal Husbandry College, Nyingchi, Tibet 860000, PR China.
authors.forename: Meng-Lin
authors.initials: ML
authors.lastname: Fan
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), Southwest University, Chongqing 400715, PR China; TAAHC-SWU Medicinal Plant R&D Center, XiZang Agriculture and Animal Husbandry College, Nyingchi, Tibet 860000, PR China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Fan
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), Southwest University, Chongqing 400715, PR China; TAAHC-SWU Medicinal Plant R&D Center, XiZang Agriculture and Animal Husbandry College, Nyingchi, Tibet 860000, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), Southwest University, Chongqing 400715, PR China; TAAHC-SWU Medicinal Plant R&D Center, XiZang Agriculture and Animal Husbandry College, Nyingchi, Tibet 860000, PR China.
authors.forename: Zhao-Yue
authors.initials: ZY
authors.lastname: Dong
authors.affiliation: School of Life Sciences, Southwest University, Chongqing 400715, PR China; TAAHC-SWU Medicinal Plant R&D Center, XiZang Agriculture and Animal Husbandry College, Nyingchi, Tibet 860000, PR China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Liao
authors.affiliation: School of Life Sciences, Southwest University, Chongqing 400715, PR China; TAAHC-SWU Medicinal Plant R&D Center, XiZang Agriculture and Animal Husbandry College, Nyingchi, Tibet 860000, PR China.
authors.forename: Xiao-Zhong
authors.initials: XZ
authors.lastname: Lan
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory on Luminescence and Real-Time Analysis (Ministry of Education), Southwest University, Chongqing 400715, PR China; TAAHC-SWU Medicinal Plant R&D Center, XiZang Agriculture and Animal Husbandry College, Nyingchi, Tibet 860000, PR China. Electronic address: mminchen@swu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
mesh_terms: D015058:1-Naphthylisothiocyanate / Q000633:toxicity*; D000208:Acute Disease; D000818:Animals; D002779:Cholestasis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D019662:Cucurbitaceae / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D038861:Medicine, Tibetan Traditional; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000032:analysis / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D010936:Plant Extracts; D015058:1-Naphthylisothiocyanate
keywords: Acute cholestasis; Antioxidant; Herpetospermum caudigerum; Long-chain fatty acids; α-naphthylisothiocyanate