title: The protection effects of (1E,6E)-1,7-diphenylhepta-1,6-diene-3,5-dione, a curcumin analogue, against operative liver injury in rats.
abstract: The relationship between the chemistry characteristic and the hepatoprotective effects of (1E,6E)-1,7-diphenylhepta-1,6-diene-3,5-dione (DDD), a curcumin analogue, in operative liver injury rats was investigated to reveal the mechanism of hepatic protection effects of DDD. DDD (1.2-4.8mmol/kg) was administrated 10min before reperfusion phase in hepatic ischemia-reperfusion injury (IRI) rats. DDD (4.8mmol/kg) administrated 10min before ischemia and N-acetylcysteine (NAC) (4.8mmol/kg) administrated 10min before reperfusion were included for comparative studies. The plasma liver enzyme activities, histopathological indices and markers of lipid peroxide were determined to evaluate the hepatic protection effects. Effects of DDD on succinate dehydrogenase (SDH) activity were also investigated. DDD showed dose-dependent hepatocyte protections when administrated 10min before reperfusion stages in hepatic IRI rats. DDD showed almost equivalent hepatoprotective effects when administrated 10min before ischemia phase demonstrating that DDD acted on the reperfusion stages selectively against the hepatic IRI, instead of ischemia phase. NAC was not effective against hepatic IRI when treated 10min before reperfusion because of the higher pKa of NAC. In additional, DDD had no effect on the SDH both in hepatic IRI rats and in mitochondria. In conclusion, DDD had dose-dependent hepatocyte protections in the reperfusion stages in hepatic IRI rats, while the observed hepatocyte protections of DDD did not involve SDH activities. β-Diketone structures of DDD were crucial for the hepatocyte protections. The abilities of DDD to clear up the unsaturated aldehydes related with the enolate nucleophilicity and the pKa. DDD might be a promising candidate to treat hepatic IRI.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China; Weifang Biomedical Innovation and Entrepreneurship Service Center, Weifang 261205, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Chi
authors.affiliation: Center for Drug Safety Evaluation and Research, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Peijing
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Qianfeng
authors.initials: Q
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Natural Medicines, Key Lab of Drug Metabolism & Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China. Electronic address: cpu_haokun@aliyun.com.
authors.forename: Kun
authors.initials: K
authors.lastname: Hao
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008297:Male; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013385:Succinate Dehydrogenase / Q000378:metabolism
chemical_list: D020011:Protective Agents; D013385:Succinate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione; D003474:Curcumin; D019803:Glutathione Disulfide
keywords: (1E,6E)-1,7-Diphenylhepta-1,6-diene-3,5-dione; Ischemia-reperfusion injury; Rat