Koo K L, Ammit A J, Tran V H, Duke C C, Roufogalis B D
Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
Thromb Res. 2001 Sep 1;103(5):387-97. doi: 10.1016/s0049-3848(01)00338-3.
Gingerols, the active components of ginger (the rhizome of Zingiber officinale, Roscoe), represent a potential new class of platelet activation inhibitors. In this study, we examined the ability of a series of synthetic gingerols and related phenylalkanol analogues (G1-G7) to inhibit human platelet activation, compared to aspirin, by measuring their effects on arachidonic acid (AA)-induced platelet serotonin release and aggregation in vitro. The IC(50) for inhibition of AA-induced (at EC(50)=0.75 mM) serotonin release by aspirin was 23.4+/-3.6 microM. Gingerols and related analogues (G1-G7) inhibited the AA-induced platelet release reaction in a similar dose range as aspirin, with IC(50) values between 45.3 and 82.6 microM. G1-G7 were also effective inhibitors of AA-induced human platelet aggregation. Maximum inhibitory (IC(max)) values of 10.5+/-3.9 and 10.4+/-3.2 microM for G3 and G4, respectively, were approximately 2-fold greater than aspirin (IC(max)=6.0+/-1.0 microM). The remaining gingerols and related analogues maximally inhibited AA-induced platelet aggregation at approximately 20-25 microM. The mechanism underlying inhibition of the AA-induced platelet release reaction and aggregation by G1-G7 may be via an effect on cyclooxygenase (COX) activity in platelets because representative gingerols and related analogues (G3-G6) potently inhibited COX activity in rat basophilic leukemia (RBL-2H3) cells. These results provide a basis for the design of more potent synthetic gingerol analogues, with similar potencies to aspirin, as platelet activation inhibitors with potential value in cardiovascular disease.
姜辣素是生姜（姜科植物姜Zingiber officinale Roscoe的根茎）的活性成分，代表了一类潜在的新型血小板激活抑制剂。在本研究中，我们通过测量一系列合成姜辣素及相关苯烷醇类似物（G1 - G7）对花生四烯酸（AA）诱导的血小板5-羟色胺释放及体外聚集的影响，与阿司匹林相比，检测了它们抑制人血小板激活的能力。阿司匹林抑制AA诱导的（在EC50 = 0.75 mM时）5-羟色胺释放的IC50为23.4±3.6 μM。姜辣素及相关类似物（G1 - G7）在与阿司匹林相似的剂量范围内抑制AA诱导的血小板释放反应，IC50值在45.3至82.6 μM之间。G1 - G7也是AA诱导的人血小板聚集的有效抑制剂。G3和G4的最大抑制（ICmax）值分别为10.5±3.9和10.4±3.2 μM，约为阿司匹林（ICmax = 6.0±1.0 μM）的2倍。其余姜辣素及相关类似物在约20 - 25 μM时最大程度地抑制AA诱导的血小板聚集。G1 - G7抑制AA诱导的血小板释放反应和聚集的潜在机制可能是通过影响血小板中的环氧化酶（COX）活性，因为代表性的姜辣素及相关类似物（G3 - G6）能有效抑制大鼠嗜碱性白血病（RBL - 2H3）细胞中的COX活性。这些结果为设计效力更强的合成姜辣素类似物提供了依据，这些类似物与阿司匹林效力相似，可作为在心血管疾病中具有潜在价值的血小板激活抑制剂。
