title: Effects of salvianolic acid B on liver mitochondria of rats with nonalcoholic steatohepatitis.
abstract: OBJECTIVE
  To investigate the effects of salvianolic acid B (Sal B) on the morphological characteristics and functions of liver mitochondria of rats with nonalcoholic steatohepatitis (NASH).
  
  
  METHODS
  A total of 60 male Sprague-Dawley rats were randomly divided into three groups: (1) a normal group fed a normal diet; (2) an NASH model group; and (3) a Sal B-treated group fed a high-fat diet. Two rats from each group were executed at the end of the 12th week to detect pathological changes. The rats in the Sal B-treated group were gavaged with 20 mL/kg Sal B (1 mg/mL) daily. The model group received an equal volume of distilled water as a control. At the end of the 24th weekend, the remaining rats were executed. Serum biochemical parameters and liver histological characteristics were observed. Malondialdehyde (MDA) and superoxide dismutase (SOD) in the liver were determined. Protein expression of CytC and caspase-3 was determined by immunohistochemistry. The mRNA transcripts of mitofusin-2 (Mfn2) and NF-κB in the liver tissue were detected by real-time PCR. Mitochondrial membrane potential was detected using a fluorescence spectrophotometer. Mitochondrial respiratory function was detected using a Clark oxygen electrode.
  
  
  RESULTS
  The model group showed significantly higher ALT, AST, TG, TC and MDA but significantly lower SOD than the normal group. In the model group, the histological characteristics of inflammation and steatosis were also evident; mitochondrial swelling and crest were shortened or even disappeared. CytC (18.46 ± 1.21 vs 60.01 ± 3.43, P < 0.01) and caspase-3 protein expression (30.26 ± 2.56 vs 83.31 ± 5.12, P < 0.01) increased significantly. The mRNA expression of NF-κB increased (0.81 ± 0.02 vs 0.91 ± 0.03, P < 0.05), whereas the mRNA expression of Mfn2 decreased (1.65 ± 0.31 vs 0.83 ± 0.16, P < 0.05). Mitochondrial membrane potential also decreased and breathing of rats was weakened. Steatosis and inflammation degrees in the treatment group were significantly alleviated compared with those of the model group. In the treatment group, mitochondrial swelling was alleviated. CytC (60.01 ± 3.43 vs 30.52 ± 2.01, P < 0.01) and caspase-3 protein expression (83.31 ± 5.12 vs 40.15 ± 3.26, P < 0.01) significantly decreased. The mRNA expression of NF-κB also decreased (0.91 ± 0.03 vs 0.74 ± 0.02, P < 0.01), whereas the mRNA expression of Mfn2 increased (0.83 ± 0.16 vs 1.35 ± 0.23, P < 0.01). Mitochondrial membrane potential increased and respiratory function was enhanced.
  
  
  CONCLUSIONS
  Sal B can treat NASH by protecting the morphological characteristics and functions of liver mitochondria, regulating lipid metabolism, controlling oxidative stress and lipid peroxidation and inhibiting apoptosis.
authors.affiliation: Ying-Chun Wang, Lei Dong, Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Ying-Chun
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Ying-Chun Wang, Lei Dong, Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Wei-Zong
authors.initials: WZ
authors.lastname: Kong
authors.affiliation: Ying-Chun Wang, Lei Dong, Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Qing-Mei
authors.initials: QM
authors.lastname: Jin
authors.affiliation: Ying-Chun Wang, Lei Dong, Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.affiliation: Ying-Chun Wang, Lei Dong, Department of Gastroenterology, the Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D020558:GTP Phosphohydrolases; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D053630:Depsides
chemical_list: D001572:Benzofurans; D015415:Biomarkers; D053148:Caspase 3; D045304:Cytochromes c; D020558:GTP Phosphohydrolases; D008315:Malondialdehyde; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D016328:NF-kappa B; D013482:Superoxide Dismutase; C076944:salvianolic acid B; D053630:Depsides; C505410:Casp3 protein, rat; C489710:Mfn2 protein, rat
keywords: Apoptosis; Liver; Mitochondria; Nonalcoholic steatohepatitis; Salvianolic acid B