Abstract: Objective: To study the anticoagulant and antithrombotic effects of total saponins from the roots of Polygala fallax Hemsl (PTS) and to elucidated the underlying mechanism. Methods: The network pharmacology method was used to predict the possible targets and pathways of PTS. The anticoagulant and antithrombotic effects of PTS in a rat model of common carotid artery thrombosis induced by FeCl3 was evaluated by examination of stained sections. The effects of PTS on activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT) and the activities of coagulation factor/cofactor FIIa and FXa were determined to uncover the anticoagulant mechanism. Results: In PTS, the content of saponin A was 1.673%. The anticoagulant targets of PTS were predicted to be coagulation factor II (FII) and platelet activating factor receptor (PTAFR). The in vivo experimental results showed that the inhibition rates of thrombosis by Xueshuantong capsule and high-dose PTS were 39.7% and 47.4%, and the thrombus area rates were 50.69% and 43.51%, respectively. The in vitro experimental results showed that in the range of 0–2 mg/mL, the concentrations of PTS required for doubling the APTT and TT of quality control human plasma were 0.36 and 0.14 mg/mL, respectively. In addition, PTS had no effect on the activity of FXa, but could inhibit the activity of FIIa in a dose-dependent manner, with a half-maximal inhibitory concentration of (85.88 ± 12.50) μg/mL. Conclusion: PTS have antithrombotic and anticoagulant effect, and the anticoagulant mechanism may be partially related to inhibiting the activity of FIIa in the intrinsic coagulation pathway.

Key words: network pharmacology; Polygala fallax Hemsl; total saponins; anticoagulant; antithrombotic