title: Protective effects of seed melon extract on CCl4-induced hepatic fibrosis in mice.
abstract: BACKGROUND
  Citrullus lanatus ssp. vulgaris var. megalaspermus Lin et Chao, was also known as watermelon belongs to family Cucurbitaceae, variously used as healthy food and in the treatment of liver and lungs problems. Currently, Citrullus lanatus has become a major economic crop of medicinal and edible effects with regional characteristics.
  
  
  OBJECTIVE
  This study was designed to evaluate the hepatoprotective and antioxidant activity of the seed melon (Citrullus lanatus ssp. vulgaris var. megalaspermus Lin et Chao) extract (SME) against carbon tetrachloride (CCl4) induced hepatic fibrosis in mice.
  
  
  METHODS
  In this study, mice were randomly divided into 7 groups, including normal control, model, silymarin tablets as the positive control, SME 100, 200, 400, and 800mg/kg. After 8 weeks, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), hyaluronic acid (HA) and laminin (LN) were checked. The levels of antioxidant enzymes such as superoxide dismutase (SOD), glutataion (GSH) and glutathione peroxidase (GSH-Px) were determined after SME administration. The hydroxyproline (HYP) levels, malondialdehyde (MDA) levels and histopathologic examinations of hepatocyte fibrosis were also determined. Additionally, effects of SME on alpha-smooth muscle actin (α-SMA) and transforming growth factor beta-1(TGF-β1) protein expressions were determined.
  
  
  RESULTS
  We found that SME could significantly lower the serum levels of hepatic enzyme markers AST, ALT, HA and LN (P<0.01). Compared with the CCl4-only treatment group, levels of hepatic SOD and GSH-Px were significantly increased, and the MDA levels were remarkably decreased in mice treated by SME at medium dose (400mg/kg) and high dose (800mg/kg) (P<0.01). A histological examination of the liver showed that lesions, including necrosis, lymphocyte infiltration and fatty degeneration, were partially healed by treatment with SME. The results of protein expressions studies displayed that SME could inhibit α-SMA and TGF-β1 protein expression (P<0.01).
  
  
  CONCLUSIONS
  The present results suggested that protective effect of SME against CCl4-induced hepatic fibrosis may rely on its effect on reducing oxidative stress and improving drug metabolizing enzyme activity in liver.
authors.affiliation: Key Laboratory of Xinjiang Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832000, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhan
authors.affiliation: Key Laboratory of Xinjiang Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832000, China; Shenyang Pharmaceutical University, Shenyang 110016, China.
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Key Laboratory of Xinjiang Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832000, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Tian
authors.affiliation: Shenzhen Fairy Lake Botanical Garden of Chinese Academy of Sciences, Shenzhen 518004, China.
authors.forename: Shi-Xiu
authors.initials: SX
authors.lastname: Feng
authors.affiliation: Shihezi Vegetable Research Institute, Shihezi 832000, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Xue
authors.affiliation: Key Laboratory of Xinjiang Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832000, China. Electronic address: 13999333713@163.com.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Tian
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D029773:Citrullus / Q000737:chemistry*; D019610:Cytoprotection; D004798:Enzymes / Q000097:blood; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D012639:Seeds / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D012838:Silymarin / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D000975:Antioxidants; D015415:Biomarkers; D004798:Enzymes; D010936:Plant Extracts; D012838:Silymarin; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; D002251:Carbon Tetrachloride; D006909:Hydroxyproline
keywords: Carbon tetrachloride; Citrullus lanatus; Hepatic fibrosis; Silymarin; Western blot