Protective Effect of Hainosankyuto, a Traditional Japanese Medicine, on Streptococcus pyogenes Infection in Murine Model 英文参考文献.docVIP

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Protective Effect of Hainosankyuto, a Traditional Japanese Medicine, on Streptococcus pyogenes Infection in Murine Model 英文参考文献.doc

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Protective Effect of Hainosankyuto, a Traditional Japanese Medicine, on Streptococcus pyogenes Infection in Murine Model 英文参考文献

ProtectiveEffectofHainosankyuto,aTraditional JapaneseMedicine,onStreptococcuspyogenesInfection inMurineModel MasaakiMinami1*,MarikoIchikawa1,NanakoHata2,TadaoHasegawa1 1Department of Bacteriology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 2Department of Microbiology, Nagoya City University Hospital,Nagoya,Japan Abstract Background: Streptococcus pyogenes (S. pyogenes) causes various serious diseases including necrotizing fasciitis and streptococcaltoxicshocksyndrome.OneseriousproblemobservedrecentlywithS.pyogenestherapyisattenuationofthe antibiotic effect, especially penicillin treatment failure and macrolide resistance. Hainosankyuto, a traditional Japanese medicinebasedonancientChinesemedicine,hasbeenusedfortreatmentofinfectiouspurulentdiseasesinJapan.Inthis study,weinvestigatedtheprotectiveandtherapeuticefficacyofHainosankyutoagainstS.pyogenes-skininfection. Methodology/PrincipalFindings:AbrothmicrodilutionmethodrevealedthatHainosankyutodidnotshowadirectanti- bacterial effect against S. pyogenes. Force-feeding Hainosankyuto to infected mice for 4 consecutive days increased the survivalrateandreducedthesizeoflocalskinlesionscomparedwithmicefedPBS.Althoughwedidnotfindthesignificant recovery of survival rate in Hainosankyuto administration only after S. pyogenes infection, the sizes of ulcer lesion were significantsmallerafterHainosankyutoadministrationcomparedwithmicefedPBS.Nodifferencewasobservedintheanti- bacterial effect of Hainosankyuto between macrolide-susceptible and -resistant strains. Blood bactericidal assay showed thatthesurvivalrateofS.pyogenesusingthebloodfromHainosankyuto-treatedmicewaslowerthanthatusingtheblood from untreated mice. We also found increased levels of IL-12, IFN-c and a decreased level of TNF-a in the serum of S. pyogenes-infectedmicetreatedwithHainosankyuto.MouseperitonealmacrophagefromHainosankyuto-treatedmicehad significantphagocyticactivityandincreasedmRNAlevelsofIL-12,IFN-canddecreasedmRNAlevelof