Effects of bicyclol on immunological liver fibrosis in rats.
Liver fibrosis results from chronic liver injury in conjunction with the accumulation of extracellular matrix proteins. The present study was performed to estimate the effect of bicyclol on bovine serum albumin (BSA)-induced immunological liver fibrosis in rats. Bicyclol (1) (100, 200, and 300 mg/kg) was given to rats by oral administration once a day for 5 weeks from the fourth week of intravenous injection of BSA. Blood and liver tissues were collected for the measurement of hydroxyproline (Hyp), procollagen type III (PIIIP), hyaluronic acid (HA), and transforming growth factor beta-1 (TGF-beta1) levels and liver pathological changes. The mRNA and protein expressions of hepatic TGF-beta1, interleukin-1 (IL-1), IL-10, MMP-2, TIMP-1, phosphorylated p38 (Pp38), and Smad2/3 were detected by reverse transcription polymerase chain reaction and Western blot. As a result, bicyclol significantly protected against BSA-induced liver fibrosis as evidenced by the reduction of elevated serum HA, PIIIP, and hepatic Hyp in rats, while liver pathological changes were also alleviated. The overexpressions of hepatic TGF-beta1, IL-1beta, IL-10, MMP-2, and TIMP-1 were suppressed by bicyclol in BSA-treated rats. The phosphorylations of Pp38 and Smad2/3 were also inhibited after bicyclol treatment. The hepatoprotection of bicyclol was mainly due to the modulation on the expression of inflammatory/anti-inflammatory cytokines, downregulation of hepatic TGF-beta1, and inhibition of hepatic collagen synthesis.
Gu
Yu
Y
The Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Zhao
Jing
J
Yao
Xiao-Min
XM
Li
Yan
Y
D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D001219:Aspartate Aminotransferases / Q000032:analysis; D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012689:Sequence Homology, Nucleic Acid; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000187:drug effects / Q000378:metabolism
D001713:Biphenyl Compounds; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D053773:Transforming Growth Factor beta1; D012710:Serum Albumin, Bovine; C477843:bicyclol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020778:Matrix Metalloproteinase 2