Methyl helicterate protects against CCl4-induced liver injury in rats by inhibiting oxidative stress, NF-κB activation, Fas/FasL pathway and cytochrome P4502E1 level.
This study was designed to investigate the protective effects of the methyl helicterate (MH) isolated from Helicteres angustifolia L. against CCl4-induced hepatotoxicities in rats. Liver injury was induced in rats by the administration of CCl4 twice a week for 8 weeks. Compared with the CCl4 group, MH significantly decreased the activities of ALT, AST and ALP in the serum and increased the activities of SOD, GSH-Px and GSH-Rd in the liver. Moreover, the content of hepatic MDA was reduced. Histological findings also confirmed the anti-hepatotoxic characterisation. In addition, MH significantly inhibited the proinflammatory mediators, such as PGE2, iNOS, COX-2, IL-6, TNF-α and myeloperoxidase (MPO). Further investigation showed that the inhibitory effect of MH on the proinflammatory cytokines was associated with the downregulation of NF-κB. Besides, MH also markedly decreased the levels of Fas/FasL protein expression and the activities of caspase-3/8, as well as the activity of cytochrome P4502E1 (CYP2E1). In brief, the protective effect of MH against CCl4-induced hepatic injury may rely on its ability to reduce oxidative stress, suppress inflammatory responses, protect against Fas/FasL-mediated apoptosis and block CYP2El-mediated CCl4 bioactivation.
Guangxi Medical University, The First Affiliated Hospital of Guangxi Traditional Chinese Medicine University, Nanning 530021, China.
Xing
X
Lin
Renbin
R
Huang
Shijun
S
Zhang
Li
L
Zheng
Ling
L
Wei
Min
M
He
Yan
Y
Zhou
Lang
L
Zhuo
Quanfang
Q
Huang
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008315:Malondialdehyde; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014315:Triterpenes / Q000494:pharmacology*; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D053222:Fas Ligand Protein; C491898:Fas protein, rat; D016328:NF-kappa B; D014315:Triterpenes; D019014:fas Receptor; C049014:methyl helicterate; D008315:Malondialdehyde; D019392:Cytochrome P-450 CYP2E1; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D015232:Dinoprostone