title: Two xanthones from Swertia punicea with hepatoprotective activities in vitro and in vivo.
abstract: BACKGROUND
  Swertia punicea Hemsl. (Gentianaceae) is more commonly known as "Ganyan-cao" and used mainly as a traditional Chinese folk medicine for the treatment of acute bilious hepatitis, cholecystitis, fever, intoxification and jaundice.
  
  
  METHODS
  The active hepatoprotective constituents of Swertia punicea were purified using various column chromatography techniques. The structures of two isolated compounds were determined on the basis of spectroscopic data interpretation such as NMR analysis. The hepatoprotective activities of isolated compounds were evaluated by using hepatotoxicity in vitro and dimethylnitrosamine-induced rat hepatic fibrosis in vivo, respectively.
  
  
  RESULTS
  Two xanthones, 1, 7-dihydroxy-3, 4, 8-trimethoxyxanthone (1) and bellidifolin (2) were isolated from the stems of Swertia punicea. The compounds 1 and 2 exhibited notable hepatoprotective activities against carbon tetrachloride (CCl4) -induced HepG2 cell damage, and effectively alleviated the levels of aspartate transaminase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malonic dialdehyde (MDA) induced by CCl₄ in a concentration-dependent manner. Co-treatment with compound 2 significantly increased the cell viability compared with N-acetyl-p-aminophenol (APAP) treatment. Compound 2 also alleviated APAP-induced hepatotoxicity by increasing glutathione (GSH) content and decreasing hydroxyl free radical (·OH) levels and reactive oxygen specises (ROS) production. In addition, the protective effect of compound 1 significantly alleviated DMN-induced liver inflammation and fibrosis. Oral administration of compound 1 recovered the reduction of albumin (ALB) and reversed the elevation of serum alanine transaminase (ALT), AST and total bilirubin (TBIL) in dimethylnitrosamine (DMN)-induced fibrotic rats. Severe oxidative stress induced in fibrotic rats was evidenced by a 1.5-fold elevation in MDA and a fall in the SOD activity, and treatment with compound 1 protected against these adverse effects. Recovery of rat liver tissue against DMN-induced hepatocellular necrosis, inflammatory changes and hepatic fibrosis by compound 1 is also confirmed by H&E and Masson stained histopathological evaluation of liver tissue.
  
  
  CONCLUSIONS
  Two xanthones from Swertia punicea exhibited hepatoprotective activities in vitro (compounds 1 and 2) and in vivo (compound 1), respectively.
authors.affiliation: National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China; Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, PR China.
authors.forename: Xi-Yuan
authors.initials: XY
authors.lastname: Zheng
authors.affiliation: National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China; Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, PR China.
authors.forename: Ying-Fan
authors.initials: YF
authors.lastname: Yang
authors.affiliation: National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China; Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, PR China.
authors.forename: Wan
authors.initials: W
authors.lastname: Li
authors.affiliation: National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Xian Nong Tan Street 1, PR China.
authors.forename: Hua
authors.initials: H
authors.lastname: Sun
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Xian Nong Tan Street 1, PR China.
authors.forename: Yue-Hua
authors.initials: YH
authors.lastname: Wang
authors.affiliation: National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, PR China. Electronic address: pxp2020@aliyun.com.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Pu
mesh_terms: D000082:Acetaminophen; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D002251:Carbon Tetrachloride; D002470:Cell Survival / Q000187:drug effects; D004128:Dimethylnitrosamine; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood / Q000378:metabolism; D020011:Protective Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D012709:Serum Albumin / Q000032:analysis; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism; D029967:Swertia; D044004:Xanthones / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C000594295:1,7-dihydroxy-3,4,8-trimethoxyxanthone; D020011:Protective Agents; D017382:Reactive Oxygen Species; D012709:Serum Albumin; D044004:Xanthones; C091291:bellidifolin; D000082:Acetaminophen; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D005978:Glutathione; D004128:Dimethylnitrosamine; D001663:Bilirubin
keywords: Acetaminophen-induced hepatotoxicity; Bellidifolin (PubChem CID: 5281623); CCl(4)-induced hepatotoxicity; DMN-induced rat hepatic fibrosis; Hepatoprotective; Swertia punicea Hemsl; Xanthones