title: Paeonol protects endotoxin-induced acute kidney injury: potential mechanism of inhibiting TLR4-NF-κB signal pathway.
abstract: METHODS
  In order to determine the therapeutic effect and mechanism of paeonol on acute kidney injury induced by endotoxin, an acute kidney injury model was established by intraperitoneal administration of lipopolysaccharide in mice in vivo and on LPS-induced dendritic cells in vitro. Renal tissues were used for histologic examination. Concentrations of blood urea nitrogen and serum creatinine were detected, inflammatory cytokines were determined by ELISA. The relative proteins' expression of TLR4-NF-κB signal pathway was assessed by Western blot, the localization and expression of phospho-NF-κB p65 in kidney was monitored by immunohistochemistry.
  
  
  RESULTS
  Treatment of paeonol successfully cuts histopathological scores and dilutes the concentrations of blood urea nitrogen and serum creatinine as index of renal injury severity. In addition, paeonol reduces pro-inflammatory cytokines and increases anti-inflammatory cytokines stimulated by LPS in a dose-dependent manner. Paeonol also inhibits the expression of phosphorylated NF-κB p65, IκBα and IKKβ, and restrains NF-κB p65 DNA-binding activity. Paeonol treatment also attenuates the effects of LPS on dendritic cells, with significant inhibition of pro-inflammatory cytokines release, then TLR4 expression and NF-κB signal pathway have been suppressed.
  
  
  CONCLUSIONS
  These results indicated that paeonol has protective effects on endotoxin-induced kidney injury. The mechanisms underlying such effects are associated with its successfully attenuate inflammatory and suppresses TLR4 and NF-κB signal pathway. Therefore, paeonol has great potential to be a novel and natural product agent for treating AKI or septic-AKI.
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
authors.affiliation: Department of Nephrology, Yu-Huang-Ding Hospital/Qingdao University, Yantai, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Qi
authors.affiliation: School of Pharmacy, Binzhou Medical University, Yantai, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Yu
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: Feng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Center for Reproductive Medicine, Tai'an Central Hospital, Tai'an, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
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: Zuo-Kai
authors.initials: ZK
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: Ming-Yan
authors.initials: MY
authors.lastname: Yang
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: Lei-Ming
authors.initials: LM
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: Da-Quan
authors.initials: DQ
authors.lastname: Chen
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: Yuan
authors.initials: Y
authors.lastname: Du
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D001806:Blood Urea Nitrogen; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D004731:Endotoxins; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation; D007668:Kidney / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; C498144:Rela protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; C013638:paeonol
keywords: NF-κB signal pathway; TLR4; acute kidney injury; paeonol; sepsis