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

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

研究成果: 雜誌貢獻文章

24 引文 斯高帕斯(Scopus)

摘要

Andrographolide, a novel nuclear factor-κB (NF-κB) 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-κB-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 μΜ)-dependently activated by andrographolide in human platelets. Andrographolide could also disrupt mitrochondrial membrane potential. In addition, caspase-8 inhibitor (z-IETD-fmk, 50 μΜ) 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.
原文英語
頁(從 - 到)1671-1677
頁數7
期刊Phytotherapy Research
27
發行號11
DOIs
出版狀態已發佈 - 2013

    指紋

ASJC Scopus subject areas

  • Pharmacology

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