Mechanisms of hepatoprotection of Terminalia catappa L. extract on D-Galactosamine-induced liver damage.
The hepatoprotective effects of the extract of Terminalia catappa L. leaves (TCE) against D-Galactosamine (D-GalN)-induced liver injury and the mechanisms underlying its protection were studied. In acute hepatic injury test, it was found that serum ALT activity was remarkably increased (3.35-fold) after injection of D-GalN in mice. But with oral pretreatment of TCE (20, 50 and 100 mg/kg/d) for 7days, change in serum ALT was notably reversed. In primary cultured hepatocytes from fetal mice, it was found that cell viability was decreased by 45.0% after addition of D-GalN, while incubation with TCE (0.1, 0.5 and 1.0 mg/ml) for 36 hours could prevent the decrease in a dose-dependent manner. Meanwhile, D-GalN-induced both the increase of AST level (1.9-fold) and the decrease of SOD activity (48.0%) in supernatant of primary cultured hepatocytes could also be inhibited by pretreatment with TCE. In order to study the possible mechanisms underlying its hepatoprotective effects, one effective component separated from TCE, 2alpha, 3beta, 23-trihydroxyursane-12-en-28-oic acid (DHUA), was used to determine anti-mitochondrial swelling activity and superoxide radicals scavenging activity in vitro. It was found that at the concentration range of 50-500 micromol/L DHUA, Ca2+ -induced mitochondrial swelling was dose-dependently inhibited, and superoxide radicals scavenging activity was also shown in a dose-dependent manner. It was concluded that TCE has hepatoprotective activity and the mechanisms underlying its protective effects may be related to the direct mitochondrion protection and strong scavenging activity on reactive oxygen species (ROS).
Institute of Materia Medica, School of Medicine, Nanjing University, Nanjing, P. R. China.
Xin-Hui
XH
Tang
Ling
L
Gao
Jing
J
Gao
Yi-Mei
YM
Fan
Li-Zhi
LZ
Xu
Xiao-Ning
XN
Zhao
Qiang
Q
Xu
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005688:Galactosamine / Q000633:toxicity; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves / Q000737:chemistry; D011247:Pregnancy; D013482:Superoxide Dismutase / Q000378:metabolism; D029766:Terminalia; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use
C499902:2alpha,3beta,23-trihydroxyursane-12-en-28-oic acid; D010936:Plant Extracts; D014315:Triterpenes; D005688:Galactosamine; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase