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

摘要: Andrographolide, a novel nuclear factor-κB (NF-κB) inhibitor, is isolated from the leaves of Andrographis paniculata. Platelet activation relevant to variety coronary heart diseases. Our recent studies revealed that andrographolide possesses potent antiplatelet activity by inhibition p38 MAPK/●HO-NF-κB-ERK2 cascade. Although platelets are anucleated cells, apoptotic machinery apparatus recently has been found regulate platelet and limit lifespan. Therefore, we further investigated regulatory effects on events. In this study, signaling events for caspase-3, -8, Bid were time (10–60 min)- dose (25–100 μΜ)-dependently activated in human platelets. Andrographolide could also disrupt mitrochondrial membrane potential. addition, caspase-8 inhibitor (z-IETD-fmk, 50 μΜ) was reverse andrographolide-induced activation, whereas antagonistic anti-Fas receptor (ZB4, 500 ng/mL) anti-tumor necrosis factor-R1 (H398, 10 µg/mL) monoclonal antibodies did not. conclusion, study first demonstrated might lifespan initiating caspase-8-dependent extrinsic pathway, spite no direct evidence death receptors involved process proved. Overall, various medicinal properties suggest its potential value treating patients with thromboembolic disorders. Copyright © 2012 John Wiley & Sons, Ltd.