title: Salvia miltiorrhiza compounds protect the liver from acute injury by regulation of p38 and NFκB signaling in Kupffer cells.
abstract: BACKGROUND
  Salvia miltiorrhiza Bunge is a traditional Asian medicine used to treat cerebral and cardiac ischemia. However, the effects of the active compounds of S. miltiorrhiza on liver damage are unclear.
  
  
  OBJECTIVE
  In this study, we tested the effects on acute liver injury of crude S. miltiorrhiza extracts from roots as well as neotanshinone B, dehydromiltirone, tanshinol A, tanshinone I, dihydrotanshinono I, neotanshinone A, cryptanshinono, tanshinone II A, and salvianolie acid B from purified S. miltiorrhiza extracts.
  
  
  METHODS
  Various compounds or ethanol extract of S. miltiorrhiza (50, 100, and 200 mg/kg, p.o.) were administered to rats for five consecutive days. After acute carbon tetrachloride (CCl4)-induced liver injury by treatment of rats with a single dose of CCl4 (0.75 mL/kg, p.o), rat liver function was tested by measuring serum biochemical parameters. Serum cytokine concentrations were assessed by enzyme-linked immunosorbent assay (ELISA). Expression of p38 and NFκB was evaluated by western blot.
  
  
  RESULTS
  All S. miltiorrhiza components showed their effects on liver function from the dose from 50 to 200 mg/kg. At the dose of 200 mg/kg, they reduced serum levels of alkaline phosphatase (ALP) by 34-77%, alanine aminotransferase (ALT) by 30-57%, aspartate aminotransferase (AST) by 43-72%, creatine total bilirubin (BIL-T) by 33-81%, albumin (ALB) by 37-67%, indicating that S. miltiorrhiza extracts protected liver from CCl4-induced damage. Moreover, S. miltiorrhiza extracts at 200 mg/kg reduced the increase in the proinflammatory cytokines tumor necrosis factor-α (TNF-α) by 25-82%, interleukin-1 (IL-1) by 42-74% and interleukin-6 (IL-6) by 67-83%, indicating an effect on alleviating liver inflammation. Furthermore, in vitro, S. miltiorrhiza extracts inhibited p38 and NFκB signaling in Kupffer cells. This effect could be a main mechanism by which S. miltiorrhiza protects against acute liver toxicity.
  
  
  CONCLUSIONS
  Active compounds of S. miltiorrhiza protected the liver from CCl4-induced injury. Protection might have been due to inhibition of p38 and NFκB signaling in Kupffer cells, which subsequently reduced inflammation in the liver.
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, the Fourth Military Medical University , Xi'an , China .
authors.forename: Shuqiang
authors.initials: S
authors.lastname: Yue
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Yue
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhifu
authors.initials: Z
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Shen
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000517:prevention & control*; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D027561:Salvia miltiorrhiza
chemical_list: D016328:NF-kappa B; D010936:Plant Extracts; D002251:Carbon Tetrachloride
keywords: Inflammation; interleukin; nuclear factor kappa B; tumor necrosis factor