The protective effect of glycyrrhetinic acid on carbon tetrachloride-induced chronic liver fibrosis in mice via upregulation of Nrf2.
This study was designed to investigate the potentially protective effects of glycyrrhetinic acid (GA) and the role of transcription factor nuclear factor-erythroid 2(NF-E2)-related factor 2 (Nrf2) signaling in the regulation of Carbon Tetrachloride (CCl(4))-induced chronic liver fibrosis in mice. The potentially protective effects of GA on CCl(4)-induced chronic liver fibrosis in mice were depicted histologically and biochemically. Firstly, histopathological changes including regenerative nodules, inflammatory cell infiltration and fibrosis were induced by CCl(4).Then, CCl(4) administration caused a marked increase in the levels of serum aminotransferases (GOT, GPT), serum monoamine oxidase (MAO) and lipid peroxidation (MDA) as well as MAO in the mice liver homogenates. Also, decreased nuclear Nrf2 expression, mRNA levels of its target genes such as superoxide dismutase 3 (SOD3), catalase (CAT), glutathione peroxidase 2 (GPX2), and activity of cellular antioxidant enzymes were found after CCl(4) exposure. All of these phenotypes were markedly reversed by the treatment of the mice with GA. In addition, GA exhibited the antioxidant effects in vitro by on FeCl(2)-ascorbate induced lipid peroxidation in mouse liver homogenates, and on DPPH scavenging activity. Taken together, these results suggested that GA can protect the liver from oxidative stress in mice, presumably through activating the nuclear translocation of Nrf2, enhancing the expression of its target genes and increasing the activity of the antioxidant enzymes. Therefore, GA may be an effective hepatoprotective agent and viable candidate for treating liver fibrosis and other oxidative stress-related diseases.
The Pharmacy of GuangDong Medical College, DongGuan, GuangDong, China.
Shaoru
S
Chen
Liyi
L
Zou
Li
L
Li
Tie
T
Wu
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001205:Ascorbic Acid / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000378:metabolism; D002908:Chronic Disease; D019610:Cytoprotection / Q000187:drug effects*; D005296:Ferrous Compounds / Q000494:pharmacology; D005466:Fluorocarbons / Q000633:toxicity*; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D018384:Oxidative Stress / Q000187:drug effects; D010851:Picrates / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D000975:Antioxidants; D001713:Biphenyl Compounds; D005296:Ferrous Compounds; D005466:Fluorocarbons; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010851:Picrates; D012333:RNA, Messenger; C035066:carbon tetrafluoride; C004931:1,1-diphenyl-2-picrylhydrazyl; D006034:Glycyrrhetinic Acid; D001205:Ascorbic Acid; C029451:ferrous chloride