title: Ethyl acetate fraction of Amomum xanthioides improves bile duct ligation-induced liver fibrosis of rat model via modulation of pro-fibrogenic cytokines.
abstract: We investigated anti-hepatofibrotic effects of ethyl acetate fraction of Ammomum xanthoides (EFAX) using bile duct ligation (BDL)-induced hepatic fibrosis in a rat model. Male SD rats (6 weeks old) underwent BDL followed by 15 days of orall administration of EFAX (12.5, 25 or 50 mg/kg) or ursodeoxycholic acid (25 mg/kg). BDL caused animal death, ascites formation, alterations in serum biochemistries, and severe hepatic injury with excessive collagen deposition, whereas EFAX treatment significantly attenuated these effects. BDL markedly increased the pro-fibrogenic cytokines (TGF-β, PDGF-β, and CTGF) and the extracellular matrix indicators α-SMA, TIMP-1 and collagen type 1 in hepatic proteins and gene expression levels, which were notably normalized by EFAX treatment. EFAX also markedly normalized pro-fibrogenic signaling molecules including Smad2/3, Smad7, Akt, p44/42, and p38. We further explored EFAX mechanisms of actions using LX-2 cells (human derived hepatic stellate cell line). Pre-treatment with EFAX drastically attenuated the activation of α-SMA and Smad2/3, which are downstream molecules of TGF-β. These findings suggest that EFAX may be a potent anti-hepatofibrotic agent, and its corresponding mechanisms primarily involve the modulation of pro-fibrogenic cytokines.
authors.affiliation: Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon, 301-724, South Korea.
authors.forename: Hyeong-Geug
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon, 301-724, South Korea.
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Han
authors.affiliation: Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon, 301-724, South Korea.
authors.forename: Jin-Seok
authors.initials: JS
authors.lastname: Lee
authors.affiliation: GyeongGi Bio-Center, GSTEP, 864-1 Iui-dong, Yeongtong-gu, Suwon, Gyeonggi-do, South Korea.
authors.forename: Jong Suk
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daehung-dong, Jung-gu, Daejeon, 301-724, South Korea.
authors.forename: Chang-Gue
authors.initials: CG
authors.lastname: Son
mesh_terms: D000085:Acetates / Q000737:chemistry / Q000494:pharmacology*; D000199:Actins / Q000235:genetics / Q000378:metabolism; D035801:Amomum / Q000737:chemistry*; D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000378:metabolism; D008026:Ligation; D015227:Lipid Peroxidation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000085:Acetates; D000199:Actins; D003094:Collagen; D016207:Cytokines; D010936:Plant Extracts; C498862:Acta2 protein, rat; C007650:ethyl acetate