title: Hepatoprotective Effects of Grape Seed Procyanidin B2 in Rats With Carbon Tetrachloride-induced Hepatic Fibrosis.
abstract: BACKGROUND
  Infectious hepatitis is a serious problem affecting millions of people worldwide, particularly in China and other developing countries, and it is the major risk factor for hepatic cirrhosis. To date, the pathogenesis of hepatic cirrhosis is complex and unclear. Traditional Chinese medicine (TCM) has long been used in its treatment; however, little is known to date about the effects of grape seed procyanidin B2 (GSPB2) on liver fibrosis.
  
  
  OBJECTIVE
  Using a rat model of carbon tetrachloride (CCl4)-induced hepatic fibrosis, the study intended to investigate the hepatoprotective effects of GSPB2 and to determine the possible pathway by which GSPB2 exerts its activities. Design • Thirty-six male, Sprague-Dawley rats were used in the study. Rats in a model (CCl4 only) group and the GSPB2 group were given CCl4 to induce hepatic fibrosis. Simultaneously, animals in the GSPB2 group were treated with GSPB2 by intragastric administration for 12 wk. In addition, the rat's Kupffer cells were cultured with CCl4 and GSPB2.
  
  
  METHODS
  The study took place at the central laboratory of Qilu Hospital at Shandong University in Jinan, China.
  
  
  METHODS
  The following parameters were investigated: (1) hepatic function; (2) the liver fibrosis index-serum hyaluronic acid (HA), laminin (LN), type 3 procollagen (PC-3), collagen 4, and hepatic hydroxyproline; (3) the expression in the liver of transforming growth factor β-1 (TGF-β1); (4) inflammatory cytokines in the liver and cell culture medium-tumor necrosis factor α (TNF-α), interleukin (IL) 1-β (IL-1β), IL-6, and IL-17; (5) oxidative stress markers in the liver and cell culture medium-malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), total superoxide dismutase (T-SOD), and total antioxidant capacity (T-AOC); and (6) levels of angiotensin 2 (Ang 2) in the liver.
  
  
  RESULTS
  The CCl4 induced (1) significant hepatic-function damage; (2) elevated levels of the measures of the liver fibrosis index, TGF-β1, inflammatory cytokines, MDA, and 8-OHdG; (3) a reduction in the activities of T-SOD and T-AOC; and (4) no effect on the level of expression of hepatic Ang 2. GSPB2 treatment partially reversed the changes induced by CCl4. The cell culture also showed that CCl4 elevated the levels of inflammatory cytokines and MDA in the Kupffer cell culture medium, whereas it reduced the activities of T-SOD and T-AOC in the medium. GSPB2 treatment partially reversed the changes induced by CCl4.
  
  
  CONCLUSIONS
  GSPB2 had hepatoprotective effects on CCl4-induced hepatic fibrosis in Sprague-Dawley rats and inhibited the inflammatory response and oxidative stress in vivo and in vitro.
authors: Zhenli
authors: Z
authors: Wang
authors: Zemin
authors: Z
authors: Zhang
authors: Ning
authors: N
authors: Du
authors: Kai
authors: K
authors: Wang
authors: Lei
authors: L
authors: Li
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D044946:Biflavonoids / Q000737:chemistry / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000633:toxicity; D002392:Catechin / Q000737:chemistry / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D056604:Grape Seed Extract / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000737:chemistry / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D044945:Proanthocyanidins / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds / Q000737:chemistry; D027843:Vitis / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D044946:Biflavonoids; D016207:Cytokines; D056604:Grape Seed Extract; D044945:Proanthocyanidins; C479580:procyanidin B2; D002392:Catechin; D002251:Carbon Tetrachloride