title: San-Cao Granule () Ameliorates Hepatic Fibrosis through High Mobility Group Box-1 Protein/Smad Signaling Pathway.
abstract: OBJECTIVE
  To investigate the possible mechanism of San-Cao Granule (SCG, ) mediating antiliver fibrosis.
  
  
  METHODS
  A total of 60 male Sprague-Dawley rats were randomly divided into the normal control group, porcine serum-treated group, ursodesoxycholic acid (UDCA, 60 mg/kg), SCG (3.6 g/kg) group, SCG (1.8 g/kg) group and SCG (0.9 g/kg) group, with 10 rats in each group. Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks, except for the normal control group. Then, the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN), and type IV collagen (IVC) were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining. Moreover, the protein expression levels of high mobility group box-1 protein (HMGB1), transforming growth factor β1 (TGF-β1), phosphorylated mothers against decapentaplegic homolog 3 (p-Smad3), Smad7, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB) and α-smooth muscle actin (α-SMA) were determined by western blot, immunohistochemistry and real time quantitative-reverse transcription polymerase.
  
  
  RESULTS
  Both SCG (3.6 and 1.8 g/kg) and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT, AST, TBIL, HA, LN and IVC and preventing the serum level reducing of ALB compared with the model group (all P<0.01). Meanwhile, the collagen deposition was attenuated by SCG and UDCA treatment. Furthermore, SCG markedly reduced the expressions of HMGB1, TGF-β1, p-Smad3, TLR4, MyD88, NF-κB and α-SMA, and enhanced the expression of the Smad7 compared with the model group (all P<0.01).
  
  
  CONCLUSIONS
  SCG ameliorates hepatic fibrosis possibly through inhibiting HMGB1, TLR4/NF-κB and TGF-β1/Smad signaling pathway.
authors.affiliation: College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.|Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Shi-Zhang
authors.initials: SZ
authors.lastname: Wei
authors.affiliation: Department of Integrative Medical Center, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Sheng-Qiang
authors.initials: SQ
authors.lastname: Luo
authors.affiliation: College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: China Military Institute of Chinese Medicine, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Jia-Bo
authors.initials: JB
authors.lastname: Wang
authors.affiliation: Animal Laboratory Center, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Rui-Sheng
authors.initials: RS
authors.lastname: Li
authors.affiliation: College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.|Chongqing Academy of Chinese Traditional Materia Medica, Key Laboratory of Chongqing Traditional Chinese Medicine Resources, Chongqing, 400065, China.
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: Chongqing Academy of Chinese Traditional Materia Medica, Key Laboratory of Chongqing Traditional Chinese Medicine Resources, Chongqing, 400065, China.
authors.forename: Yan-Lei
authors.initials: YL
authors.lastname: Guo
authors.affiliation: College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.|Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Chang
authors.initials: C
authors.lastname: Chen
authors.affiliation: College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.|Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.affiliation: College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.|Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Integrative Medical Center, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Hong-Hong
authors.initials: HH
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.|Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Zhi-Rui
authors.initials: ZR
authors.lastname: Yang
authors.affiliation: Department of Integrative Medical Center, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Jian-Yu
authors.initials: JY
authors.lastname: Li
authors.affiliation: Department of Integrative Medical Center, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Rui-Lin
authors.initials: RL
authors.lastname: Wang
authors.affiliation: China Military Institute of Chinese Medicine, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Ya-Ming
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: Department of Integrative Medical Center, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Hui-Yin
authors.initials: HY
authors.lastname: Yang
authors.affiliation: China Military Institute of Chinese Medicine, 302 Hospital of People's Liberation Army, Beijing, 100039, China.
authors.forename: Xiao-He
authors.initials: XH
authors.lastname: Xiao
authors.affiliation: College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. zhaoyl22855@163.com.|Department of Pharmacy, 302 Hospital of People's Liberation Army, Beijing, 100039, China. zhaoyl22855@163.com.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Zhao
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D024243:HMGB1 Protein; C000629062:San-Cao granules; D051785:Smad Proteins
keywords: San-Cao Granule; high mobility group box-1 protein; liver fibrosis; toll-like receptor 4/nuclear factor-kappa B; transforming growth factor β1/mothers against decapentaplegic homolog