title: 2'-Hydroxyflavanone ameliorates mesenteric angiogenesis and portal-systemic collaterals in rats with liver fibrosis.
abstract: OBJECTIVE
  Portal-systemic collaterals lead to dreadful consequences in patients with cirrhosis. Angiogenesis participates in the development of liver fibrosis, hyperdynamic circulation, and portal-systemic collaterals. 2'-Hydroxyflavanone (2'-HF), one of the citrus fruits flavonoids, is known to have antiangiogenesis effect without adverse response. However, the relevant effects in liver fibrosis have not been surveyed.
  
  
  METHODS
  Male Wistar rats received thioacetamide (TAA, 100 mg/kg tiw, i.p.) for 6 weeks to induce liver fibrosis. On the 29th to 42nd day, rats randomly received 2'-HF (100 mg/kg, qod, i.p.) or vehicle (corn oil). On the 43rd day, after hemodynamic measurements, the followings were surveyed: (i) severity of collaterals; (ii) mesenteric angiogenesis; (iii) mesenteric proangiogenic factors protein expressions; (iv) Mesenteric vascular endothelial cells apoptosis; and (v) Mesenteric expressions of proteins regulating apoptosis.
  
  
  RESULTS
  Compared with the vehicle group, 2'-HF did not significantly change body weight, mean arterial pressure, heart rate, and portal pressure in TAA rats. 2'-HF significantly alleviated the severity of collaterals, but the mesenteric phospho-ERK, ERK, phospho-Akt, Akt, COX1, COX2, VEGF, and VEGFR-2 protein expressions were not altered. The apoptotic index of 2'-HF group was significantly higher and the mesenteric protein expressions of pro-apoptotic factors, NFkB 50, NFkB 65, Bax, phospho-p53, 17 kD cleaved caspase 3, and 17 kD casepase 3 were up-regulated.
  
  
  CONCLUSIONS
  2'-HF does not influence the hemodynamics but alleviated the severity of collaterals in rats with liver fibrosis and early portal hypertension. This is, at least partly, attributed to enhanced apoptosis of mesenteric vascular endothelial cells.
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.|Endoscopy Center for Diagnosis and Treatment, Taipei, Taiwan.
authors.forename: I-Fang
authors.initials: IF
authors.lastname: Hsin
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Teh-Ia
authors.initials: TI
authors.lastname: Huo
authors.affiliation: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.|Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Fa-Yauh
authors.initials: FY
authors.lastname: Lee
authors.affiliation: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.|Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hui-Chun
authors.initials: HC
authors.lastname: Huang
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.|Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shao-Jung
authors.initials: SJ
authors.lastname: Hsu
authors.affiliation: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.|Department of Medical Affair and Planning, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Sun-Sang
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.|Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Ho
authors.affiliation: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.|Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Han-Chieh
authors.initials: HC
authors.lastname: Lin
authors.affiliation: Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.|Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan.
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Lee
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D042501:Angiogenic Proteins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D003097:Collateral Circulation / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D044950:Flavanones / Q000494:pharmacology*; D006975:Hypertension, Portal / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008643:Mesentery / Q000098:blood supply*; D018919:Neovascularization, Physiologic; D011168:Portal System / Q000187:drug effects* / Q000503:physiopathology; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D013853:Thioacetamide
chemical_list: C520534:2'-hydroxyflavanone; D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D051017:Apoptosis Regulatory Proteins; D044950:Flavanones; D013853:Thioacetamide
keywords: angiogenesis; flavonoids; liver fibrosis; portal-systemic collaterals; vascular endothelial growth factor