title: Puerarin exerts antipyretic effect on lipopolysaccharide-induced fever in rats involving inhibition of pyrogen production from macrophages.
abstract: BACKGROUND
  Puerarin is the most abundant isoflavonoid in Radix Puerariae (Gegen), which has been prescribed as a medicinal herb for treating fever in China for a long history.
  
  
  OBJECTIVE
  The present study aimed at evaluating the antipyretic effect of puerarin and revealing the related mechanisms.
  
  
  METHODS
  Lipopolysaccharide (LPS)-induced fever in rats was used to assess the antipyretic effect of puerarin. After an intraperitoneal injection of LPS (100μg/kg), body temperature was tested every 30min up to 8h. Different doses of puerarin (25, 50, 100mg/kg) were intraperitoneally administered 30min before LPS injection. In vitro, LPS-stimulated RAW 264.7 cells were treated with various concentrations of puerarin (25-200μM). The pyrogenic mediators, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E(2) (PGE(2)) and nitric oxide (NO), were examined on both transcription and expression levels. Furthermore, the influences of the activation of nuclear factor-kappa B (NF-κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs) by puerarin were assayed by western blot.
  
  
  RESULTS
  The intraperitoneal administration of puerarin at test doses clearly demonstrated apparent antipyretic effect through the declines in body temperature elevated by LPS in rats. The in vitro data showed that puerarin inhibited the production of IL-1β, TNF-α, IL-6, PGE(2) and NO; moreover, the RT-PCR analysis and the western blot analysis indicated that puerarin regulated the transcriptional level via suppression of NF-κB activation and blockade of MAPK signal pathway.
  
  
  CONCLUSIONS
  In summary, the antipyretic property of puerarin might result, at least in part, from an inhibition of endogenous pyrogen production and expression. Taken in this sense, our findings provide an explanation for puerarin acting as an important constituent in Gegen, thus, provide scientific basis for the wide use of Radix Puerariae in China as a traditional antipyretic.
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Xiu-Juan
authors.initials: XJ
authors.lastname: Yao
authors.forename: Ji-Ai
authors.initials: JA
authors.lastname: Yin
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Xia
authors.forename: Zhi-Feng
authors.initials: ZF
authors.lastname: Wei
authors.forename: Yu-Bin
authors.initials: YB
authors.lastname: Luo
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Carlos
authors.initials: C
authors.lastname: Feleder
authors.forename: Yue
authors.initials: Y
authors.lastname: Dai
mesh_terms: D000818:Animals; D058633:Antipyretics / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D001833:Body Temperature Regulation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D005786:Gene Expression Regulation; D018836:Inflammation Mediators / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007529:Isoflavones / Q000008:administration & dosage / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D058633:Antipyretics; D018836:Inflammation Mediators; D007529:Isoflavones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012333:RNA, Messenger; C482199:lipopolysaccharide, E coli O55-B5; D020928:Mitogen-Activated Protein Kinases; C033607:puerarin