Recent studies have showed that thrombosis is closely related to leucocytes involved in immunity.Interfering with the binding of leukocyte integrin Mac-1 and platelet GPIbα can inhibit thrombosis without affecting physiological coagulation.Mac-1-GPIbα is proposed as a potential safety target for antithrombotic agents.Guanxinning tablet(GXNT)is an oral Chinese patent medi-cine used for the treatment of angina pectoris,which contains phenolic acid active ingredients,such as salvianolic acids,ferulic acid,chlorogenic acid,caffeic acid,rosmarinic acid,tanshinol,and protocatechualdehyde.Our previous studies demonstrated that GXN ex-hibited significant antithrombotic effects,and clinical studies suggested that it did not increase bleeding risk.In addition,GXN exerted a significantly regulatory effect on immune inflammation.In the current study,we intended to evaluate the effects of GXN on bleed-ing events and explore the safety antithrombotic mechanism of GXN based on leukocyte-platelet interaction.First,we established a gastric ulcer model induced by acetic acid in rats and found that GXN not only did not increase the degree of gastrointestinal bleeding when gastric ulcer occurred,but also had a certain promoting effect on the healing of gastric ulcer.Second,in vitro experiments showed that after pretreatment with GXN and activation by phorbol 12-myristate-13-acetate(PMA),the adhesion and aggregation of leukocytes with human platelets were reduced.It was also found that GXN reduced the expression and activation of Mac-1 in leuco-cytes,and inhibited platelet activation due to leukocyte engagement via Mac-1.Overall,the results suggest that GXN may be a safe an-tithrombotic agent,and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interac-tion target Mac-1-GPIbα.

YANG Qin-Qin;FANG Ming-Sun;TU Jue;MA Quan-Xin;SHEN Li-Ye;XU Yan-Yun;CHEN Jie;CHEN Min-Li

Academy of Chinese Medicine&Institute of Comparative Medicine,Zhejiang Chinese Medical University,Hangzhou 310053,China;Department of Experimental Animals,Zhejiang Academy of Traditional Chinese Medicine,Hangzhou 310007,China;Department of Vasculocardiology,the First Affiliated Hospital of Zhejiang Chinese Medicine University,Hangzhou 310006,China

中国天然药物

[1]YANG Qin-Qin;FANG Ming-Sun;TU Jue;MA Quan-Xin;SHEN Li-Ye;XU Yan-Yun;CHEN Jie;CHEN Min-Li-.Guanxinning tablet inhibits the interaction between leukocyte integ-rin Mac-1 and platelet GPIbα for antithrombosis without increased bleeding risk)[J].中国天然药物,2022(08):589-600

Guanxinning,GPIb,antithrombosis,Interfering,GXNT,tanshinol,GXN,leuco,tithrombotic

tablet,inhibits,interaction,between,Mac,without,increased,bleeding,risk,Recent,studies,have,showed,that,closely,related,leucocytes,involved,immunity,binding,integrin,affecting,physiological,coagulation,proposed,potential,safety,target,antithrombotic,agents,oral,Chinese,patent,medi,cine,used,angina,pectoris,which,contains,phenolic,active,ingredients,such,salvianolic,acids,ferulic,chlorogenic,caffeic,rosmarinic,protocatechualdehyde,Our,previous,demonstrated,effects,clinical,suggested,did,not,addition,exerted,significantly,regulatory,immune,inflammation,current,study,intended,evaluate,events,explore,mechanism,First,established,gastric,ulcer,model,induced,by,acetic,rats,found,only,degree,gastrointestinal,when,occurred,but,also,had,certain,promoting,healing,Second,vitro,experiments,after,pretreatment,activation,phorbol,myristate,acetate,PMA,adhesion,aggregation,leukocytes,human,platelets,were,reduced,It,was,expression,inhibited,due,engagement,Overall,results,may,low,probably

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