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典型文献
Danshensu alleviates pseudo-typed SARS-CoV-2 induced mouse acute lung inflammation
文献摘要:
Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)can induce acute inflammatory response like acute lung inflammation(ALI)or acute respiratory distress syndrome,leading to severe progression and mortality.Therapeutics for treatment of SARS-CoV-2-triggered respiratory inflammation are urgent to be discovered.Our previous study shows that Salvianolic acid C potently inhibits SARS-CoV-2 infection.In this study,we investigated the antiviral effects of a Salvia miltiorrhiza compound,Danshensu,in vitro and in vivo,including the mechanism of S protein-mediated virus attachment and entry into target cells.In authentic and pseudo-typed virus assays in vitro,Danshensu displayed a potent antiviral activity against SARS-CoV-2 with EC50 of 0.97 μM,and potently inhibited the entry of SARS-CoV-2 S protein-pseudo-typed virus(SARS-CoV-2 S)into ACE2-overexpressed HEK-293T cells(IC50=0.31 μM)and Vero-E6 cell(IC50=4.97 μM).Mice received SARS-CoV-2 S via trachea to induce ALI,while the VSV-G treated mice served as controls.The mice were administered Danshensu(25,50,100 mg/kg,i.v.,once)or Danshensu(25,50,100mg-kg-1·d-1,oral administration,for 7 days)before SARS-CoV-2 S infection.We showed that SARS-CoV-2 S infection induced severe inflammatory cell infiltration,severely damaged lung tissue structure,highly expressed levels of inflammatory cytokines,and activated TLR4 and hyperphosphorylation of the NF-κB p65;the high expression of angiotensinogen(AGT)and low expression of ACE2 at the mRNA level in the lung tissue were also observed.Both oral and intravenous pretreatment with Danshensu dose-dependently alleviated the pathological alterations in mice infected with SARS-CoV-2 S.This study not only establishes a mouse model of pseudo-typed SARS-CoV-2(SARS-CoV-2 S)induced ALI,but also demonstrates that Danshensu is a potential treatment for COVID-19 patients to inhibit the lung inflammatory response.
文献关键词:
作者姓名:
Wei Wang;Sha-sha Li;Xin-feng Xu;Chan Yang;Xiao-ge Niu;Shu-xian Yin;Xiao-yan Pan;Wei Xu;Guo-dong Hu;Chan Wang;Shu-wen Liu
作者机构:
Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China;Department of Respiratory and Critical Care Medicine,Nanfang Hospital,Southern Medical University,Guangzhou 510515,China;State Key Laboratory of Virology,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan 430071,China;State Key Laboratory of Organ Failure Research,Guangdong Provincial Institute of Nephrology,Southern Medical University,Guangzhou 510515,China
引用格式:
[1]Wei Wang;Sha-sha Li;Xin-feng Xu;Chan Yang;Xiao-ge Niu;Shu-xian Yin;Xiao-yan Pan;Wei Xu;Guo-dong Hu;Chan Wang;Shu-wen Liu-.Danshensu alleviates pseudo-typed SARS-CoV-2 induced mouse acute lung inflammation)[J].中国药理学报(英文版),2022(04):771-780
A类:
Danshensu
B类:
alleviates,pseudo,typed,SARS,CoV,induced,mouse,acute,lung,inflammation,Severe,respiratory,syndrome,coronavirus,can,inflammatory,response,like,ALI,distress,leading,progression,mortality,Therapeutics,triggered,are,urgent,discovered,Our,previous,study,shows,that,Salvianolic,acid,potently,inhibits,infection,In,this,investigated,antiviral,effects,miltiorrhiza,compound,vitro,vivo,including,mechanism,protein,mediated,attachment,entry,into,target,cells,authentic,assays,displayed,activity,against,EC50,inhibited,ACE2,overexpressed,HEK,293T,IC50,Vero,E6,Mice,received,trachea,while,VSV,treated,mice,controls,were,administered,once,100mg,oral,administration,days,before,We,showed,infiltration,severely,damaged,tissue,structure,highly,levels,cytokines,activated,TLR4,hyperphosphorylation,p65,expression,angiotensinogen,AGT,low,also,observed,Both,intravenous,pretreatment,dose,dependently,alleviated,pathological,alterations,infected,This,not,only,establishes,model,but,demonstrates,potential,patients
AB值:
0.502596
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