Protective effects of chalcone derivatives for acute liver injury in mice.
The hepatoprotective effects of chalcone derivatives were evaluated in D-galactosamine/lipopolysaccharide (D-GalN/LPS)-induced fulminant hepatic failure in mouse. Thirteen chalcone derivatives were synthesized for study and their hepatoprotective effects were evaluated by assessing aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in serum. Chalcone preparations were injected into mice at 12 h and 1 h before intraperitoneal injection of D-GalN/LPS. After abdominal administration, changes in AST and ALT between the control and treated groups were observed. Ten of the synthesized chalcone derivatives exhibited inhibitory effects on D-GalN/LPS-induced levels of AST and ALT in mice. Compounds 2, 3, 8, 9, and 12 markedly reduced serum AST and ALT at 8 h, inhibited hepatocyte necrosis and showed significant hepatoprotective activities. The activity of compound 3 was compared with the bifendate (DDB) through oral administration. Compound 3 showed much higher inhibitory effects than bifendate for decreasing AST and ALT activity. The results indicate that compound 3 has strong hepatoprotective activity through suppression of tumor necrosis factor-alpha (TNF-alpha) preduction, reduction of the histological change in the liver, and attenuated of hepatocyte apoptosis confirmed by DNA fragmentation assay.
Guan
Li-Ping
LP
College of Pharmacy, Yan bian University, Yanji City, Jilin Province 133000, PR China.
Nan
Ji-Xing
JX
Jin
Xue-Jun
XJ
Jin
Qing-Hao
QH
Kwak
Kyung Chell
KC
Chai
Kyu-yun
KY
Quan
Zhe-Shan
ZS
D000818:Animals; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017114:Liver Failure, Acute / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
D020011:Protective Agents; D002599:Chalcone