Zhang Qili, Wang Danlin, Zhang Meiyan, Zhao Yunli, Yu Zhiguo
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
PLoS One. 2017 Jan 20;12(1):e0170334. doi: 10.1371/journal.pone.0170334. eCollection 2017.
R-/S-2-(2-Hydroxypropanamido) benzoic acid (R-/S-HPABA), a marine-derived anti-inflammatory drug, however, the antiplatelet and antithrombotic effects have not been investigated. In this paper, the in vitro antiplatelet activities and in vivo antithrombotic effects of R-/S-HPABA were investigated, for the first time. The effects of R-/S-HPABA on platelet aggregation induced by adenosine diphosphate (ADP), collagen (COLL) and arachidonic acid (AA) were evaluated. In addition, the in vivo bleeding time, clotting time, collagen-epinephrine induced pulmonary thrombosis and common carotid artery thrombosis were also investigated in rats. R-/S-HPABA significantly inhibited ADP, COLL and AA induced platelet aggregation in rabbit platelet rich plasma in vitro compared with control group, to a degree similar to that of aspirin. Besides, R-/S-HPABA prolonged bleeding time and clotting time as well as increased the recovery rate obviously in pulmonary thrombosis. Moreover, the level of thromboxane B2 (TXB2) was decreased while the production of 6-keto-prostaglandin F1α (6-keto-PGF1α) was increased markedly by R-/S-HPABA. Furthermore, R-/S-HPABA reduced carotid artery thrombosis weight. These results illustrated that R-/S-HPABA could be a potent antiplatelet aggregation and antithrombotic agent.
R-/S-2-(2-羟基丙酰胺基)苯甲酸(R-/S-HPABA)是一种海洋来源的抗炎药物,然而,其抗血小板和抗血栓形成作用尚未得到研究。本文首次研究了R-/S-HPABA的体外抗血小板活性和体内抗血栓形成作用。评估了R-/S-HPABA对二磷酸腺苷(ADP)、胶原(COLL)和花生四烯酸(AA)诱导的血小板聚集的影响。此外,还在大鼠体内研究了出血时间、凝血时间、胶原-肾上腺素诱导的肺血栓形成和颈总动脉血栓形成。与对照组相比,R-/S-HPABA在体外显著抑制了兔富血小板血浆中ADP、COLL和AA诱导的血小板聚集,其抑制程度与阿司匹林相似。此外,R-/S-HPABA延长了出血时间和凝血时间,并显著提高了肺血栓形成的恢复率。而且,R-/S-HPABA显著降低了血栓素B2(TXB2)水平,同时提高了6-酮-前列腺素F1α(6-酮-PGF1α)的生成。此外,R-/S-HPABA减轻了颈动脉血栓重量。这些结果表明,R-/S-HPABA可能是一种有效的抗血小板聚集和抗血栓形成药物。