黃耆萃取物抑制人類血小板活性之分子機轉探討

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題名:	黃耆萃取物抑制人類血小板活性之分子機轉探討 Molecular mechanisms underlying the antiplatelet activity of Astragali Radix extracts
作者:	陳亭宇 CHEN, TING-YU
貢獻者:	醫學科學研究所碩士班呂婉榕
關鍵詞:	黃耆萃取物;血小板活化 Astragali Radix extracts;platelet activation
日期:	2023-06-19
上傳時間:	2023-12-15 14:05:25 (UTC+8)
摘要:	血栓的形成與血小板活化有著密不可分關聯，其亦在心血管疾病中扮演著相當重要的角色。目前抗血栓藥物對血栓栓塞型疾病的治療十分有效；然而，由於其嚴重的副作用，使得這些藥物在使用上被侷限。Calycosin (Cal)和Formononetin (For)是傳統中草藥黃耆(Fisch.)的主要萃取物，具有多種功效，如抗氧化、抗腫瘤、抗發炎和神經保護等。但是，兩種萃取物對血小板的活化作用仍不清楚，因此，本研究在探討Cal和For在血小板活化和血栓形成中的詳細機制。在這項研究中，使用血小板凝集試驗和西方墨點法來探討Cal和For在體外對血小板活化的影響。結果顯示，Cal (5-20 ?M)和For (10-50 ?M)會抑制由collagen (1 ?g/mL)所誘導的血小板活化，但對thrombin (0.02 U/mL)與U46619 (thromboxane A2類似物，1 ?M)卻沒有影響。此外，Cal 會抑制MAPKs、AKT、PKC以及PLC2的磷酸化，並影響血小板顆粒釋放。在動物實驗中也顯示Cal會減少血栓的形成，且不具有出血的副作用。我們研究結果表明，Cal能預防或是治療血栓栓塞型疾病的潛在藥物。 Thrombus formation, a phenomenon primarily related to increased platelet activation, plays a key role in cardiovascular and cerebrovascular diseases. Antithrombotic agents show considerable benefits for the treatment of thromboembolic diseases; however, these agents still have substantial limitations due to their serious side-effect. calycosin and formononetin, traditional Chinese herb Astragalus membranaceus (Fisch.), exhibit multiple biological activities such as anti-oxidant, anti-tumor, anti?inflammation, and neuroprotection. However, the role of Cal and For on platelet activation remains unclear. Thus, this study aimed to investigate the detailed mechanism of Cal and For in platelet activation and thrombus formation. In this study, platelet aggregation and immunoblotting analysis were used to investigate the effects of Cal and For on platelet activation ex vivo. Our data revealed that Cal (5-20 ?M) and For (10-50 ?M) exhibited more potent activity in inhibiting platelet aggregation stimulated by collagen (1 ?g/mL) but not thrombin (0.02 U/mL) and U46619 (thromboxane A2 analogue, 1 ?M). In addition, Cal inhibited mitogen-activated protein kinases (MAPKs), AKT, protein kinase C (PKC) and PLC2 activation and subsequent granule release. In vivo, Cal reduced the thrombus formation and did not induce bleeding in mice. The findings of our study suggest that Cal is a potential therapeutic agent for preventing or treating thromboembolic disorders.
描述:	碩士指導教授:呂婉榕委員:呂婉榕委員:楊志豪委員:謝政穎
資料類型:	thesis
顯示於類別:	[醫學科學研究所] 博碩士論文

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