title: Preventive effect of halofuginone on concanavalin A-induced liver fibrosis.
abstract: Halofuginone (HF) is an active component of extracts derived from the plant alkaloid febrifugine and has shown therapeutic promise in animal models of fibrotic disease. Our main objectives were to clarify the suppressive effect of HF on concanavalin A (ConA)-induced liver fibrosis. ConA injection into the tail vein caused a great increase in the serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, while orally administration of HF significantly decreased the levels of the transaminases. In addition, the levels of hyaluronic acid (HA), procollagen III (PCIII) and TGF-β1 in the serum and collagen I, α-SMA, tissue inhibitors of metalloproteinase 2 (TIMP2) and Smad3 in the liver tissue were significantly lowered with the treatment of HF. Histological examination also demonstrated that HF significantly reduced the severity of liver fibrosis. Since ConA-induced liver fibrosis is caused by the repeated activation of T cells, immunomodulatory substances might be responsible for the suppressive effect of HF. We found that the production of nuclear factor (NF)-kB in the serum was increased in ConA-treated group, while decreased significantly with the treatment of HF. The changes of inflammatory cytokines tumor necrosis factor (TNF-α), IL-6 and IL-1β in the serum followed the same rhythm. All together, our findings indicate that orally administration HF (10ppm) would attenuate the liver fibrosis by suppressing the synthesis of collagen I and inflammation-mediated liver injury.
authors.affiliation: Department of Immunology, Medical College of Qingdao University, Qingdao, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Immunology, Medical College of Qingdao University, Qingdao, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Anatomy, Medical College of Qingdao University, Qingdao, China.
authors.forename: Ruo-wu
authors.initials: RW
authors.lastname: Shen
authors.affiliation: Department of Radiology, Affiliated Hospital of Qingdao University Medical College, Qingdao, China.
authors.forename: Jia-Bao
authors.initials: JB
authors.lastname: Liu
authors.affiliation: Department of Immunology, Medical College of Qingdao University, Qingdao, China.
authors.forename: Mei-hua
authors.initials: MH
authors.lastname: Gao
authors.affiliation: Department of Immunology, Medical College of Qingdao University, Qingdao, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Immunology, Medical College of Qingdao University, Qingdao, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Li
authors.affiliation: Department of Immunology, Medical College of Qingdao University, Qingdao, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003208:Concanavalin A; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D052999:Quinazolinones / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000097:blood
chemical_list: D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D015850:Interleukin-6; D010880:Piperidines; D052999:Quinazolinones; D053773:Transforming Growth Factor beta1; D003208:Concanavalin A; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C010176:halofuginone