Study On The Antithrombotic Effects Of Caragana Jubata(Pall.) Poir

Many traditional Chinese herbs which called drugs for "activating the blood circulation to remove blood stasis" have antithrombotic effects,and play an important role in the treatment of cardiovascular and cerebrovascular diseases.Caragana jubata(Pall.)Poir.is traditionally used in Tibetan medicine primarily for promoting blood circulation and dissipating blood stasis.However,there are no reports about its antithrombotic effects.The present experiment have explored the effects of Caragana jubata on thrombosis and the possible mechanism and constituents of action.Anti-thrombotic effects of Caragana jubata ethanol extract(TE)were evaluated by animal models including acute pulmonary thrombosis in mice,carotid artery thrombosis and inferior vena cava thrombosis in rats.To clarify the mechanism of antithrombosis,effects of TE on bleeding time,coagulation system,content of NO in rat serum as well as P-selectin in plasma were also measured.Besides,in order to search the bioactive fractions of TE,solid phase extract(SPE)was applied to obtain the two main fractions(TE-1 and TE-2).Pharmacological effects of TE-1 and TE-2 were compared on tail bleeding time,clotting time and acute pulmonary thrombosis in mice.Reference substances were applied to identify the main compounds of TE.UPLC/DAD-q-TOF-MS analysis was conducted to identify the categories of the chemical compounds in the two main fractions.Results indicated that TE in all doses could significantly reduce the thrombus weight in carotid artery thrombosis(P < 0.001)and in inferior vena cava thrombosis(P < 0.01)compared with the control group.TE could also protect the mice from paralysis or death(P < 0.05)in medium and high doses.Besides,TE could significantly prolong the bleeding time(P < 0.01),clotting time(P < 0.05),PT(P < 0.01)and APTT(P < 0.05),meanwhile increase NO content in rat serum(P < 0.05)and decrease P-selectin level in rat plasma(P < 0.05)compared with the control group.The pharmacological effects of TE-1 fraction and TE-2 fraction showed that both TE-1 fraction and TE-2 fraction could prolong the bleeding time and clotting time,and protect the mice from pulmonary thrombosis,especially for TE-2 fraction.6 compounds of TE were identified by the reference substances.Categories of 25 constituents in TE-1 and TE-2 were identified by UPLC/DAD-q-TOF-MS analysis.Constituents in TE-1 were mainly stilbenoids,while those in TE-2 were mainly isoflavones and pterocarpans.It was inferred that all of these three kinds of constituents may be responsible for the antithrombotic effects of Caragana jubata,especially for isoflavones and pterocarpans,which would provide a support for the application of the plant in traditional Tibetan medicine and also could contribute to the exploration of new antithrombotic drugs.