title: p38 MAPK signal pathway involved in anti-inflammatory effect of Chaihu-Shugan-San and Shen-ling-bai-zhu-San on hepatocyte in non-alcoholic steatohepatitis rats.
abstract: BACKGROUND
  Traditional Chinese Medicine (TCM), has over thousands-of-years history of use. Chaihu-Shugan-San (CSS), and Shen-ling-bai-zhu-San (SLBZS), are famous traditional Chinese herbal medicine formulas, which have been used in China, for the treatment of many chronic diseases.
  
  
  METHODS
  This study investigated the anti-inflammatory effects of CSS and SLBZS on signaling molecules involved in p38 mitogen-activated protein kinase (p38 MAPK), pathway on hepatocytes of non-alcoholic steatohepatitis (NASH), rats induced by high fat diet. SD male rats were randomly divided into 8 groups: negative control group, model control group, high (9.6g/kg/day)/low (3.2g/kg/day)-dose CSS group, high (30g/kg/day)/low (10g/kg/day)-dose SLBZS group, high (39.6g/kg/day)/low (13.2g/kg/day)-dose integrated group. The rats of NASH model were induced by feeding a high-fat diet. After 16, wks, Hepatocytes were isolated from 6, rats in each group by collagenase perfusion. The liver histopathological changes and serum inflammatory cytokines TNF-α, IL-6 were determined. The proteins of TLR4, phosphor-p38 MAPK and p38 MAPK involved in p38 MAPK signal pathway were assayed.
  
  
  RESULTS
  The statistical data indicated the NASH model rats reproduced typical histopathological features of NASH in human. CSS and SLBZS ameliorated lipid metabolic disturbance, attenuated NASH progression, decreased the levels of TNF-α and IL-6 in serum, as well as inhibited TLR4 protein expression, p38 MAPK phosphorylation, and activation of p38 MAPK. In conclusion, CSS and SLBZS might work as a significant anti-inflammatory effect on hepatocyte of NASH by inhibiting the activation of TLR4, p-p38 MAPK and p38 MAPK involved in p38 MAPK signal pathway.
  
  
  CONCLUSIONS
  To some extent, CSS and SLBZS may be a potential alternative and complementary medicine to protect against liver injury, alleviate the inflammation reaction, moderate NASH progression.
authors.affiliation: Department of Traditional Chinese Medicine, Medical College of Jinan University, 601 Huangpu Road West, Guangzhou, Guangdong, China, 510632.
authors.forename: QinHe
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Traditional Chinese Medicine, Medical College of Jinan University, 601 Huangpu Road West, Guangzhou, Guangdong, China, 510632.
authors.forename: YongJian
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Traditional Chinese Medicine, Medical College of Jinan University, 601 Huangpu Road West, Guangzhou, Guangdong, China, 510632.
authors.forename: GaoFei
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Pathophysiology, Medical College of Jinan University, 601 Huangpu Road West, Guangzhou, Guangdong, China, 510632.
authors.forename: ChaoFeng
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Traditional Chinese Medicine, Medical College of Jinan University, 601 Huangpu Road West, Guangzhou, Guangdong, China, 510632.
authors.forename: YuPei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Traditional Chinese Medicine, Medical College of Jinan University, 601 Huangpu Road West, Guangzhou, Guangdong, China, 510632.
authors.forename: ShaoBing
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Pathophysiology, Medical College of Jinan University, 601 Huangpu Road West, Guangzhou, Guangdong, China, 510632.
authors.forename: YanPing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Traditional Chinese Medicine, Medical College of Jinan University, 601 Huangpu Road West, Guangzhou, Guangdong, China, 510632.
authors.forename: XiangWen
authors.initials: X
authors.lastname: Gong
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D059305:Diet, High-Fat; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D019684:Magnoliopsida; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D015850:Interleukin-6; D010936:Plant Extracts; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C497000:chaihu-shugan-san; C532982:shen ling bai zhu; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Chaihu-Shugan-San (CSS); Hepatocytes; Non-alcoholic Steatohepatitis; Shen-ling-bai-zhu-San (SLBZS); Toll like receptor 4; Traditional Chinese medicine; p38 mitogen-activated protein kinase