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

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1671-1677
Number of pages7
JournalPhytotherapy Research
Volume27
Issue number11
DOIs
Publication statusPublished - 2013

Keywords

  • andrographolide
  • Bid
  • caspase-3
  • caspase-8
  • mitochondrial membrane potential
  • platelets

ASJC Scopus subject areas

  • Pharmacology

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