Analysis of the mechanisms of Guanxinning Tablet for antithrombotic and microthrombotic effects caused by COVID-19 based on network pharmacology
Thrombosis is a key factor that increases the mortality rate of COVID-19 patients and causes long COVID sequelae.Guanxinning Tablet(GXNT),which is composed of Salvia miltiorrhiza and Ligusticum Chuanxiong,has significant antithrombotic activity,but the similarities and differences between its anti-conventional thrombus and microthrombus induced by COVID-19 remain unclear.In this paper,the main active components,potential targets and mechanisms of GXNT in the treatment of thrombus and microthrombus caused by COVID-19 were preliminarily revealed by using anti-platelet experiments in vitro,network pharmacology analysis,molecular docking technology and molecular biology experiments.The results of platelet aggregation and adhesion experiments in vitro showed that GXNT had significant anti-platelet aggregation and adhesion activities in a dose-dependent manner.Using network pharmacology analysis,it was revealed that salvianolic acid B,tanshinone ⅡA,caffeic acid and ligustrazine in GXNT could resist thrombus and microthrombus caused by COVID-19 through key targets as the high mobility group box 1 protein(HMGB1),tumor necrosis factor(TNF),interleukin 6(IL6)and AKT serine/threonine kinase 1(AKT1).HMGB1 signaling pathway is one of its key common mechanisms.Western blot also indicated that GXNT significantly inhibited the expression of HMGB1 protein in platelets.In summary,this paper explores the similarities and differences between the mechanism of GXNT against conventional thrombus and microthrombus caused by COVID-19 and provides drug reference and theoretical basis for clinical prevention and treatment of long COVID sequelae.The animal experiment has been approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine(No.TCM-LAEC2023187g1549).