title: Osthole protects sepsis-induced acute kidney injury via down-regulating NF-κB signal pathway.
abstract: OBJECTIVE
  As a natural coumarin derivative from the Cnidium monnieri(L)Cusson fruit, osthole consists of 7-methoxy-8-isopentenoxy-coumarin. The purpose of this research is to study the mechanism and effect of osthole on sepsis-induced acute kidney injury.
  
  
  METHODS
  The protective effect of osthole on mouse macrophage RAW 264.7 and HK-2 cells induced by LPS in vitro and on acute kidney injury model induced by sepsis and established by puncture and cecal ligation (CLP) in vivo were tested.
  
  
  RESULTS
  Osthole (20, 40 mg·kg-1) group can greatly attenuate the changes of the score and kidney histopathology damage and enhance the survival time of septic mice. After the CLP surgery, degrees of SCr and BUN related to kidney injury were upregulated. The concentrations of SCr and BUN can be greatly reduced by treatment with osthole. Furthermore, osthole could increase bacterial killing activity and phagocytic activities of macrophages impaired after CLP partly and attenuate blood bacterial counts and leukocyte infiltration markedly. Furthermore, osthole can suppress NF-κB signal pathway through the inhibition of the nuclear translocation by regulating phosphorylation of IκBα and IKKβ and hinder the production of chemoattractant (MCP-1 and IL-8) and proinflammatory cytokines (TNF-α, IL-1β and IL-6).
  
  
  CONCLUSIONS
  Mainly because of its immunomodulatory properties and anti-inflammatory activity, which might be closely associated with suppression of the stimulation of the NF-κB signal pathway, osthole has protective effect on sepsis-induced kidney injury. It can be seen from such evidence that osthole can be potentially applied in the treatment of acute kidney injury.
authors.affiliation: School of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Nephrology, Yu-Huang-Ding Hospital/Qingdao University, 264000 Yantai, Shandong, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Nephrology, Yu-Huang-Ding Hospital/Qingdao University, 264000 Yantai, Shandong, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Qi
authors.affiliation: Yantai Food and Drug Inspection Center, 264000 Yantai, Shandong, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Binzhou Medical University, 264003 Yantai, Shandong, P.R. China.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Qu
authors.affiliation: Yantai Yan-Tai-Shan Hospital, Yantai, Shandong, P.R. China.
authors.forename: Yue-Juan
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, P.R. China.
authors.forename: Xue-Kai
authors.initials: XK
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, P.R. China.
authors.forename: Hua-Ying
authors.initials: HY
authors.lastname: Fan
mesh_terms: D058186:Acute Kidney Injury / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D003374:Coumarins / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D000067996:RAW 264.7 Cells; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D003374:Coumarins; D016328:NF-kappa B; C046627:osthol
keywords: CLP; NF-κB signal pathway; acute kidney injury; osthole; sepsis