酚類抗氧化劑芝麻酚可經由NF-kB和MAPKs路徑來調節抗血小板的作用機轉

Sesamol, a phenolic antioxidant, acts as regulator of NF-kB and MAPKs-mediated antiplatelet effects

在急性冠心症患者的治療中，抗血小板藥物扮演重要的角色。現今由於經皮冠狀動脈介入手術次數和其併發症增加，其中動脈血栓形成是主因，所以必須用抗血小板藥物來治療。目前的抗血小板療法對預防血栓併發症非常有效。然而，由於藥物動力學和藥物的相互作用、遺傳體質造成血栓的增加，越來越多的患者儘管使用抗血小板藥物，仍然發生血栓的併發症。因此，最近研究已經提供新的抗血小板藥物具有更好的抗血栓功能，而不會增加出血風險。芝麻酚是一種從芝麻脂質中提取的膳食化合物，具有自由基清除和抗氧化特性。芝麻酚因其抗氧化和細胞保護特性，對高脂血症、抗高血壓和脂質過氧化有效。我們之前的研究發現，芝麻酚具有強大的抗血小板活性，藉由活化環狀單磷酸腺苷（cAMP）-磷酸化內皮型一氧化氮合成酶（eNOS）/一氧化氮（NO）-環磷酸鳥苷cGMP的路徑和抑制磷脂酶C（PLC）γ2，蛋白激酶C（PKC）- p38絲裂原活化蛋白激酶p38 MAPK-血栓素A2（TxA2）的路徑。另外我們的研究還發現，這種化合物具有抑制核因子活化B細胞κ輕鏈增強子（NF-κB）的訊號傳遞來發揮抗血小板活性。在此篇文獻回顧，我們特別研究芝麻醇是經由NF-κB/MAPK和PLC的路徑來產生抗血小板作用。

 

Antiplatelet therapy plays a crucial role in medical treatment for patients with acute coronary syndrome. Since percutaneous coronary interventions increase in number and complication, more patients must be treated with antiplatelet therapy for cardiovascular diseases in which arterial thrombosis plays a key role. Present an-tiplatelet therapy is greatly effective in preventing atherothrombotic complications. However, the increased number of patients remain to experience persistent complica-tions although being correctly treated, because of pharmacokinetics and interactions of drugs, genetic background and increased thrombus formation. Therefore, several massive research efforts have taken to offer new antiplatelet drugs with better defen-sive properties without any bleeding risk. Sesamol, a dietary compound derived from sesame lignans, has free radical scavenging and antioxidant properties. Sesamol is effective for hyperlipidemia, antihypertension and lipid peroxidation due to its anti-oxidant and cytoprotective properties. We found that sesamol has potent antiplatelet activity via activation of cyclic adenosine monophosphate (cAMP)- endothelial nitric oxide synthase (eNOS)/ nitric oxide (NO)-cGMP pathway and inhibition of phospho-lipase C (PLC)γ2, protein kinase C (PKC) -p38 MAPK-thromboxane A2 (TxA2). Our another study also found that this compound inhibits nuclear factor-kappa B (NF-κB) signaling events to exert its antiplatelet activity. In this review, we summarize the sesamol’s antiplatelet effect through NF-κB/MAPK and PLC signaling pathways.