黄花倒水莲总皂苷抗凝血和抗血栓作用及机制：基于网络药理学

目的：研究黄花倒水莲总皂苷（total saponin of Polygala fallax Hemsl，PTS）的抗凝血、抗血栓作用及机制。方法：网络药理学方法筛选分析预测出PTS可能作用的靶点及通路。利用FeCl3诱导大鼠颈总动脉血栓模型，通过染色切片结果来验证PTS的抗凝血、抗血栓作用。测定PTS对活化部分凝血活酶时间（activated partial thromboplastin time，APTT）、凝血酶时间（thrombin time，TT）、凝血酶原时间（prothrombin time，PT）的影响及凝血因子II（coagulation factor II，FII）a和辅因子X（cofactor X，FX）a活性的影响，初步确定其抗凝血作用机制。结果：PTS中皂苷A质量分数为1.673%。经网络药理学预测PTS的抗凝血作用靶点为FII和血小板活化因子受体（platelet activating factor receptor，PTAFR）。体内动物实验结果表明，血栓通胶囊组和高剂量PTS组的血栓形成抑制率分别为39.7%和47.4%，血栓面积率分别为50.69%和43.51%。体外实验结果表明，在0～2 mg/mL范围内，PTS延长人质控血浆APTT、TT所需质量浓度分别为0.36 mg/mL和0.14 mg/mL，FIIa和FΧa活力检测实验结果表明，PTS对FΧa的活力无影响，可剂量依赖性地抑制FIIa活力，其半数抑制质量浓度（half-maximal inhibitory concentration，IC50）为（85.88±12.50）μg/mL。结论：体内外实验证明，PTS具有抗血栓和抗凝血作用，抗凝血作用机制之一为抑制内源性凝血途径上FIIa的活性。

Anticoagulant and Antithrombotic Effect and Underlying Mechanism of Total Saponins from the Roots of Polygala fallax Hemsl: A Study Based on Network Pharmacology

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.