Mechanisms of andrographolide-induced platelet apoptosis in human platelets: regulatory roles of the extrinsic apoptotic pathway

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题名:	Mechanisms of andrographolide-induced platelet apoptosis in human platelets: regulatory roles of the extrinsic apoptotic pathway
作者:	Li-Ming Lien;Cheng-Chen Su;Wen-Hsien Hsu;Wan-Jung Lu;Chi-Li Chung;Ting-Lin Yen;Hou-Chang Chiu;Joen-Rong Sheu;Kuan-Hung Lin
贡献者:	視光學系
关键词:	andrographolide;caspase-3;caspase-8;Bid;mitochondrial membrane potential;platelets
日期:	2013-11-01
上传时间:	2025-08-01 15:07:06 (UTC+8)
摘要:	Andrographolide, a novel nuclear factor-?B (NF-?B) inhibitor, is isolated from the leaves of Andrographis paniculata. Platelet activation is relevant to a variety of coronary heart diseases. Our recent studies revealed that andrographolide possesses potent antiplatelet activity by inhibition of the p38 MAPK/?HO-NF-?B-ERK2 cascade. Although platelets are anucleated cells, apoptotic machinery apparatus recently has been found to regulate platelet activation and limit platelet lifespan. Therefore, we further investigated the regulatory effects of andrographolide on platelet apoptotic events. In this study, apoptotic signaling events for caspase-3, -8, and Bid were time (10?60?min)- and dose (25?100???)-dependently activated by andrographolide in human platelets. Andrographolide could also disrupt mitrochondrial membrane potential. In addition, caspase-8 inhibitor (z-IETD-fmk, 50???) was found to reverse andrographolide-induced caspase-8 activation, whereas the antagonistic anti-Fas receptor (ZB4, 500?ng/mL) and anti-tumor necrosis factor-R1 (H398, 10?µg/mL) monoclonal antibodies did not. In conclusion, this study for the first time demonstrated that andrographolide might limit platelet lifespan by initiating the caspase-8-dependent extrinsic apoptotic pathway, in spite of no direct evidence that death receptors are involved in this process proved. Overall, the various medicinal properties of andrographolide suggest its potential value in treating patients with thromboembolic disorders. Copyright ? 2012 John Wiley & Sons, Ltd.
關聯:	Phytotherapy Research, 27(11), 1671-1677. https://doi.org/10.1002/ptr.4911
显示于类别:	[視光學系] 期刊論文

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