Jin Wen Yi, Kim Seung-Hyung, Kim Ho Kyoung, Jang Dong Gyu, Nam Jeong Bum, Kang Young Min, Hwang Bang Yeon, Kim Dong-Seon
KOC Biotech Inc., Daejeon 306-791, South Korea.
Institute of Traditional Medicine and Bioscience, Daejeon University, Daejeon 300-716, South Korea.
Integr Med Res. 2013 Jun;2(2):70-75. doi: 10.1016/j.imr.2013.04.005. Epub 2013 Apr 23.
Agents currently used for the treatment and prevention of thrombosis have a number of side effects. We conducted this study to develop antithrombotic agents from herbs that are used in food.
The 80% (v/v) ethanol extracts of leaf (PL) and Mume Fructus (MF) and their combinations-2:1 (PM21), 1:1 (PM11), and 1:2 (PM12)-were evaluated on rat platelet aggregation induced by adenosine diphosphate (ADP) and on arteriovenous shunt thrombosis after 3 days of oral treatment in rats .
At 100 μg/mL, PM21 and PM11 inhibited ADP-induced aggregation by 44.0 ± 4.3% and 30.0 ± 3.2%, respectively, whereas PL, MF, and PM12 weakly or scarcely inhibited ADP-induced aggregation by 3.9 ± 3.2%, 13.0 ± 2.7%, and 5.2 ± 1.3%, respectively. The IC values of PM21 on ADP-, collagen-, and thrombin-induced platelet aggregations were 135.6 ± 7.4 μg/mL, 142.7 ± 5.8 μg/mL, and 186.5 ± 9.7 μg/mL, respectively. In an rat arteriovenous-shunt thrombosis model, thrombus weight was significantly decreased after the oral administration of 400 mg/kg PL (27.8 ± 3.0%, < 0.01) or MF (35.2 ± 2.1%, < 0.01), and with a good accord to the results, the combination of PL and MF in the ratio of 2:1, PM21 (60.9 ± 1.2%, < 0.001), showed a superior antithrombotic effect to those of individual extracts. At dosages of 200 mg/kg, 100 mg/kg, and 50 mg/kg, PM21 dose-dependently decreased thrombosis weight (ED, 314 mg/kg).
These results suggest that combination preparations of PL and MF, especially their 2:1 combination, can increase antiplatelet and antithromboticeffects more than PL and MF alone, offering evidence for a potential novel combination antithrombotic therapy.
目前用于治疗和预防血栓形成的药物有许多副作用。我们开展本研究以从食用草药中开发抗血栓药物。
对紫苏叶(PL)和乌梅(MF)的80%(v/v)乙醇提取物及其组合——2:1(PM21)、1:1(PM11)和1:2(PM12)——进行评估,观察其对二磷酸腺苷(ADP)诱导的大鼠血小板聚集的影响,以及在大鼠口服给药3天后对动静脉分流血栓形成的影响。
在100μg/mL时,PM21和PM11分别抑制ADP诱导的聚集44.0±4.3%和30.0±3.2%,而PL、MF和PM12对ADP诱导的聚集抑制作用较弱或几乎没有抑制作用,分别为3.9±3.2%、13.0±2.7%和5.2±1.3%。PM21对ADP、胶原和凝血酶诱导的血小板聚集的IC值分别为135.6±7.4μg/mL、142.7±5.8μg/mL和186.5±9.7μg/mL。在大鼠动静脉分流血栓形成模型中,口服400mg/kg PL(27.8±3.0%,P<0.01)或MF(35.2±2.1%,P<0.01)后血栓重量显著降低,与结果相符的是,PL和MF按2:1比例组合的PM21(60.9±1.2%,P<0.001)显示出比单一提取物更强的抗血栓作用。在200mg/kg、100mg/kg和50mg/kg剂量下,PM21剂量依赖性降低血栓重量(ED50,314mg/kg)。
这些结果表明,PL和MF的组合制剂,尤其是其2:1组合,比单独的PL和MF能增强抗血小板和抗血栓作用,为潜在的新型联合抗血栓治疗提供了证据。