Chlorogenic acid against carbon tetrachloride-induced liver fibrosis in rats.
This study examined the effects of chlorogenic acid (CGA) on liver fibrosis induced by carbon tetrachloride (CCl(4)) and explored the possible mechanisms of action. Liver fibrosis was induced in male Sprague-Dawley (SD) rats by the injection of 40% CCl(4) subcutaneously twice a week for eight weeks. At the same time, CGA (60 and 30mg/kg) was administered intragastrically once daily to a subset of rats. Upon pathological examination, the CGA-treated rats showed significantly reduced liver damage and symptoms of liver fibrosis. The expression of collagen I and collagen III mRNA was increased markedly by the CCl(4) treatment but this increase was suppressed by CGA. As compared with the CGA-treated group, the expression of bcl-2, vascular endothelial growth factor (VEGF), and transforming growth factor (TGF-beta1) mRNA was increased in CCl(4) group, whereas Bax mRNA expression decreased. The expression of Bax and bcl-2 protein was confirmed by western blotting. Intragastric administration of CGA reduced the protein expression of alpha-smooth muscle actin (alpha-SMA) and glucose-regulated proteins 78 and 94 (GRP78 and GRP94) in rats injured by treatment with CCl(4). Our data indicate that CGA can efficiently inhibit CCl(4)-induced liver fibrosis in rats. Therefore, CGA could be an effective drug for preventing liver fibrosis.
Shi
Hongyang
H
Department of Gastroenterology, Second Affiliate Hospital of Xian Jiao Tong University, Xian 710004, China. Shihy2003@126.com
Dong
Lei
L
Bai
Yanhua
Y
Zhao
Juhui
J
Zhang
Yong
Y
Zhang
Li
L
D000199:Actins / Q000378:metabolism; D000818:Animals; D002251:Carbon Tetrachloride / Q000378:metabolism / Q000633:toxicity; D002726:Chlorogenic Acid / Q000378:metabolism / Q000627:therapeutic use*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D008099:Liver / Q000473:pathology / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D020011:Protective Agents / Q000378:metabolism / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP
D000199:Actins; D002251:Carbon Tetrachloride; D002726:Chlorogenic Acid; D024042:Collagen Type I; D024061:Collagen Type III; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D042442:Vascular Endothelial Growth Factors; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C018551:glucose-regulated proteins; C498862:Acta2 protein, rat