title: Protective effect of diarylheptanoids from Curcuma comosa on primary rat hepatocytes against t-butyl hydroperoxide-induced toxicity.
abstract: BACKGROUND
  Curcuma comosa Roxb. (Zingiberaceae) has traditionally been used as an anti-inflammatory agent in liver, and recent study has shown its hepatoprotective effect against CCl4-induced liver injury in vivo.
  
  
  OBJECTIVE
  This study further assesses the protective effect of C. comosa extracts and its isolated compounds against tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in isolated primary rat hepatocytes.
  
  
  METHODS
  Isolated primary hepatocytes were pretreated with either ethanol (5-50 μg/ml) or hexane extract (1-50 μg/ml), or two diarylheptanoids (4-35 μM): compound D-91 [1-(4-hydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol] and compound D-92 [(3S)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol], from C. comosa for 2 h prior to exposure to 1.5 mM t-BHP for 15 and 30 min. Their hepatoprotective activities were then determined.
  
  
  RESULTS
  t-BHP markedly caused the formation of MDA and ALT leakage from the hepatocytes. Pretreatment with the C. comosa ethanol extract showed greater protective effect than the hexane extract, and the effect was concentration related. Treating the hepatocytes with compound D-92 provided greater protective effect than compound D-91. IC50 values of compounds D-91, D-92, and silymarin for the protection of ALT leakage at 30 min were 32.7 ± 1.1, 9.8 ± 0.7, and 160 ± 8 μM, respectively. Further investigation showed that compound D-92 was more effective in maintaining the intracellular glutathione content in the t-BHP treated group, whereas the reduction in antioxidant enzymes, glutathione peroxidase and glutathione-S-transferase activities, were not improved.
  
  
  CONCLUSIONS
  Results suggest that diarylheptanoids are the active principles that provide protection against t-BHP-induced injury. Their ability to maintain intracellular glutathione content is the main mechanisms underlying the protective action.
authors.affiliation: a Department of Physiology , Faculty of Science, Mahidol University , Bangkok , Thailand .
authors.forename: Kanoknetr
authors.initials: K
authors.lastname: Suksen
authors.affiliation: a Department of Physiology , Faculty of Science, Mahidol University , Bangkok , Thailand .|b Toxicology Graduate Program, Faculty of Science, Mahidol University , Bangkok , Thailand .
authors.forename: Tumnoon
authors.initials: T
authors.lastname: Charaslertrangsi
authors.affiliation: a Department of Physiology , Faculty of Science, Mahidol University , Bangkok , Thailand .|b Toxicology Graduate Program, Faculty of Science, Mahidol University , Bangkok , Thailand .
authors.forename: Chadanat
authors.initials: C
authors.lastname: Noonin
authors.affiliation: a Department of Physiology , Faculty of Science, Mahidol University , Bangkok , Thailand .
authors.forename: Surawat
authors.initials: S
authors.lastname: Jariyawat
authors.affiliation: c Pharmacology Unit, Department of Medical Science , Faculty of Science, Rangsit University, Pathum Thani , Thailand .
authors.forename: Watcharaporn
authors.initials: W
authors.lastname: Devakul Na Ayutthaya
authors.affiliation: d Department of Chemistry , Faculty of Science, Ramkamhaeng University , Bangkok , Thailand .
authors.forename: Apichart
authors.initials: A
authors.lastname: Suksamrarn
authors.affiliation: e Department of Chemistry , Faculty of Science, Mahidol University , Bangkok , Thailand , and.
authors.forename: Patoomratana
authors.initials: P
authors.lastname: Tuchinda
authors.affiliation: a Department of Physiology , Faculty of Science, Mahidol University , Bangkok , Thailand .|f Chakri Naruebodindra Medical Institute, Faculty of Medicine, Ramathibodi Hospital, Mahidol University , Bangkok , Thailand.
authors.forename: Pawinee
authors.initials: P
authors.lastname: Piyachaturawat
mesh_terms: D000818:Animals; D030024:Curcuma; D036381:Diarylheptanoids / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D020011:Protective Agents / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
chemical_list: D036381:Diarylheptanoids; D010936:Plant Extracts; D020011:Protective Agents; D020122:tert-Butylhydroperoxide
keywords: Antioxidant; glutathione; hepatoprotection; primary hepatocytes