Objective:To screen the active components from Fuzheng Huayu Recipe(FZHY)and redesign a new recipe composed of the active components,and validate the effect of active components formulation from FZHY against liver fibrosis.Methods:Thirty-two components from FZHY were evaluated for their activities against liver fibrosis respectively,with 6 kinds of cell models in vitro,including oxidative stressed hepatocyte in L-02,hypoxia injured/proliferative hepatic sinusoidal endothelial cells in SK-HEP-1 and human hepatic sinusoidal endothelial cells(HHSEC),and activated hepatic stellate cell in LX-2.The comprehensive activity of each component against liver fibrosis was scored according to the role of original herbs in FZHY and cell functions in fibrogenesis.Totally 7 active components were selected and combined with equal proportion to form a novel active components formulation(ACF).The efficacy of ACF on liver fibrosis were evaluated on activation of LX-2 and proliferation of HHSEC in vitro and in liver fibrosis model mice induced by dimethylnitrosamine(DMN).Totally 72 mice were divided into 6 groups using a random number table,including normal,high-dose ACF control(20 μmol/Lx7 components/kg body weight),model,low-,medium-,high-dose ACF groups(5,10,20 μmol/Lx7 components/kg body weight,respectively).Hematoxylin eosin and Sirius red stainings were used to observe inflammation and fibrosis change of liver tissue;scanning electron microscopy(SEM)and transmission electron microscopy(TEM)were utilized to observe the effect of ACF on ultrastructure of hepatic sinusoids.Results:Fifteen components from FZHY showed higher scores for their activity on against liver fibrosis.Among them,7 components including tanshinone ⅡA,salvianolic acid B,cordycepin,amygdalin,quercetin,protopanaxatriol,and schizandrin B were recombined with equal proportions to form ACF.ACF at 1,2,4 μ mol/L showed strong inhibitory effects on activation of LX-2 and proliferation of HHSEC in vitro(all P＜0.01).Compared with the model group,ACF attenuated liver collagen deposition,improved sinusoidal capillarization in a dose-dependent manner(all P＜0.05).Conclusions:ACF exerts a satisfactory effect against experimental liver fibrosis and attenuates sinusoidal capillarization,which warrant a further research and development for herbal components formulation on liver fibrosis.

SUN Xin;TAN Ye;LYU Jing;LIU Hong-liang;ZHAO Zhi-min;LIU Cheng-hai

Institute of Liver Diseases,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai(201203),China;Shanghai Key Laboratory of Traditional Chinese Clinical Medicine,Shanghai(201203),China

中国结合医学杂志（英文版）

[1]SUN Xin;TAN Ye;LYU Jing;LIU Hong-liang;ZHAO Zhi-min;LIU Cheng-hai-.Active Components Formulation Developed from Fuzheng Huayu Recipe for Anti-Liver Fibrosis)[J].中国结合医学杂志（英文版）,2022(06):538-544

FZHY,HHSEC,dimethylnitrosamine,Lx7,stainings,sinusoids,protopanaxatriol,schizandrin,capillarization

Active,Components,Formulation,Developed,from,Fuzheng,Huayu,Recipe,Anti,Liver,Fibrosis,Objective,screen,active,components,redesign,new,recipe,composed,validate,formulation,against,liver,fibrosis,Methods,Thirty,two,were,evaluated,their,activities,respectively,kinds,models,vitro,including,oxidative,stressed,hepatocyte,hypoxia,injured,proliferative,hepatic,sinusoidal,endothelial,cells,SK,HEP,human,activated,stellate,LX,comprehensive,activity,each,was,scored,according,role,original,herbs,functions,fibrogenesis,Totally,selected,equal,novel,ACF,efficacy,activation,proliferation,mice,induced,by,DMN,divided,into,groups,using,random,number,table,normal,dose,control,body,weight,low,medium,Hematoxylin,eosin,Sirius,used,observe,inflammation,change,tissue,scanning,electron,microscopy,transmission,TEM,utilized,ultrastructure,Results,Fifteen,showed,higher,scores,Among,them,tanshinone,salvianolic,acid,cordycepin,amygdalin,quercetin,recombined,proportions,strong,inhibitory,effects,Compared,attenuated,collagen,deposition,improved,dependent,manner,Conclusions,exerts,satisfactory,experimental,attenuates,which,warrant,further,research,development,herbal

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