title: Artesunate ameliorates hepatic fibrosis induced by bovine serum albumin in rats through regulating matrix metalloproteinases.
abstract: The effect of Artesunate on anti-hepatic fibrosis was discovered by our team for the first time. In order to investigate the effect of Artesunate on hepatic fibrosis induced by Bovine serum albumin (BSA) in rats and understand the initiatory mechanism of its effect, several experiments were conducted in this assay. HE staining and Masson׳s Trichrome staining were employed in observation of morphological changes. The content of hydroxyproline in the hepatic tissue was determined by using an acid hydrolyzation method. In addition, the expression of Matrix metalloproteinase-13 (MMP-13) and type I collagen were tested by western blotting respectively. The expression of Matrix metalloproteinase-2(MMP-2), Matrix metalloproteinase-9 (MMP-9) were determined by Gelatin Zymography Assay. Also, we use immunohistochemical studies to measure the expression of α-SMA. The final results indicated that Artesunate could dramatically attenuate the extent of hepatic fibrosis showed by histopathological sections of hepatic tissues, significantly decrease the content of hydroxyproline and efficiently inhibit the protein expression of MMP-2, MMP-9, α-SMA and type I collagen. Artesunate could as well promote the expression of MMP-13 at the same time. In conclusion, the results not only suggested that Artesunate could ameliorate hepatic fibrosis, but also suggested the anti-fibrogenic mechanisms of Artesunate might be associated with inhibiting the activation of HSCs, decreasing the expression of MMP-2, MMP-9 and increasing the expression of MMP-13.These results would bring new insights for the treatment for hepatic fibrosis.
authors.affiliation: Department of Pharmacology, Tianjin Medical University, TianJin, China; Department of Pharmacy, Second Affiliated Hospital of Tianjin University of TCM, Tianjin, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Tianjin Medical University, TianJin, China.
authors.forename: Wendong
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Tianjin Medical University, TianJin, China. Electronic address: fangdch1962@163.com.
authors.forename: Buwu
authors.initials: B
authors.lastname: Fang
authors.affiliation: Department of Pharmacology, Tianjin Medical University, TianJin, China; ICU of Transplantation, Tianjin First Center Hospital, Tianjin, China.
authors.forename: Sinan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Pharmacology, Tianjin Medical University, TianJin, China; Clinical Nutrition Department, Tangdu Hospital, the Fourth Military Medical University, Xi'an, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D024042:Collagen Type I / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000009:adverse effects*
chemical_list: D000199:Actins; D037621:Artemisinins; D000077332:Artesunate; D024042:Collagen Type I; D020782:Matrix Metalloproteinases; D012710:Serum Albumin, Bovine; C498862:Acta2 protein, rat
keywords: Artesunate; Hepatic fibrosis; Hepatic stellate cell; Matrix metalloproteinases-13; Matrix metalloproteinases-2; Matrix metalloproteinases-9; α-SMA