Guanxinning tablet inhibits the interaction between leukocyte integrin Mac-1 and platelet GPIbαfor antithrombosis without increased bleeding risk

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 GPIbαcan inhibit thrombosis without affecting physiological coagulation.Mac-1-GPIbαis proposed as a potential safety target for antithrombotic agents.Guanxinning tablet(GXNT)is an oral Chinese patent medicine 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 exhibited 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 bleeding 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 vitroexperiments 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 leucocytes,and inhibited platelet activation due to leukocyte engagement via Mac-1.Overall,the results suggest that GXN may be a safe antithrombotic agent,and its low bleeding risk mechanism is probably related to inhibited leukocyte-platelet aggregation and its interaction target Mac-1-GPIbα.

Network Pharmacology-Based Exploration of the Mechanism of Guanxinning Tablet for the Treatment of Stable Coronary Artery Disease

Objective:Network pharmacology was utilized to explore the mechanism of Guanxinning(GXN)tablet for the treatment of stable coronary artery disease(SCAD).Materials and Methods:First,active ingredients and therapeutic targets were predicted by databases and gene chip.Then,we constructed the compound-target(C-T)network and target-disease(T-D)network to screen hub compounds and therapeutic targets based on contribution index(CI),degree,closeness,betweenness,and coreness in the networks.Enrichment analysis was performed on hub therapeutic targets,and finally,the verification of hub ingredients and hub therapeutic targets was performed through molecular docking.Results:With"oral bioavailability≥30%,druglikeness≥0.18,and half-life≥4 h"as screening conditions,58 active ingredients were obtained.Seven hundred and seventeen compound targets and 636 SCAD targets were retrieved using databases and gene chip,and the intersection of both(139 targets)was defined as therapeutic targets.According to CI,degree,betweenness,closeness,and coreness,2 hub compounds and 13 hub therapeutic targets were chosen from the C-T network and T-D network,respectively.The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that GXN treated SCAD from several aspects including inflammatory reaction,oxidative stress,nutritional metabolism,blood pressure regulation,ventricular remodeling,vascular smooth muscle proliferation,angiogenesis,and platelet aggregation.Tissue enrichment analysis revealed that the therapeutic targets were enriched in multiple organs and tissues.The excellent binding force between the hub compounds and hub therapeutic targets was verified by molecular docking.Conclusions:The treatment of SCAD by GXN has the characteristics of multiple ingredients,multiple targets,and multiple approaches.Consequently,it may theoretically treat SCAD from multiple angles and levels.