Choi Jun-Hui, Park Se-Eun, Kim Sung-Jun, Kim Seung
Department of Life Science & BK21-Plus Research Team for Bioactive Control Technology, Gwangju, 501-759, Republic of Korea.
Department of Alternative Medicine, Gwangju University, Gwangju, 503-703, Republic of Korea.
Biochimie. 2015 Aug;115:177-86. doi: 10.1016/j.biochi.2015.06.001. Epub 2015 Jun 12.
The objectives of the present study were to investigate whether kaempferol affects pro-coagulant proteinase activity, fibrin clot formation, blood clot and thrombin (or collagen/epinephrine)-stimulated platelet activation, thrombosis, and coagulation in ICR (Imprinting Control Region) mice and SD (Sprague-Dawley) rats. Kaempferol significantly inhibited the enzymatic activities of thrombin and FXa by 68 ± 1.6% and 52 ± 2.4%, respectively. Kaempferol also inhibited fibrin polymer formation in turbidity. Microscopic analysis was performed using a fluorescent conjugate. Kaempferol completely attenuated phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and phosphoinositide 3-kinase (PI3K)/PKB (AKT) in thrombin-stimulated platelets and delayed aggregation time (clotting) by 34.6% in an assay of collagen/epinephrine-stimulated platelet activation. Moreover, kaempferol protected against thrombosis development in 3 animal models, including collagen/epinephrine- and thrombin-induced acute thromboembolism models and an FeCl3-induced carotid arterial thrombus model. The ex vivo anticoagulant effect of kaempferol was further confirmed in ICR mice. This study demonstrated that kaempferol may be clinically useful due to its ability to reduce or prevent thrombotic challenge.
本研究的目的是调查山奈酚是否会影响ICR（印记控制区）小鼠和SD（Sprague-Dawley）大鼠的促凝血蛋白酶活性、纤维蛋白凝块形成、血液凝固以及凝血酶（或胶原/肾上腺素）刺激的血小板活化、血栓形成和凝血。山奈酚分别显著抑制凝血酶和FXa的酶活性68±1.6%和52±2.4%。山奈酚还抑制了纤维蛋白聚合物的浊度形成。使用荧光共轭物进行显微镜分析。在凝血酶刺激的血小板中，山奈酚完全减弱了细胞外信号调节激酶（ERK）1/2、p38、c-Jun氨基末端激酶（JNK）1/2以及磷酸肌醇3激酶（PI3K）/蛋白激酶B（AKT）的磷酸化，并在胶原/肾上腺素刺激的血小板活化试验中使聚集时间（凝血）延迟了34.6%。此外，山奈酚在3种动物模型中预防了血栓形成，包括胶原/肾上腺素和凝血酶诱导的急性血栓栓塞模型以及FeCl3诱导的颈动脉血栓模型。山奈酚在ICR小鼠中的体外抗凝作用得到了进一步证实。这项研究表明，山奈酚因其具有减少或预防血栓形成挑战的能力，可能在临床上具有应用价值。
