The antiplatelet activity of magnolol is mediated by PPAR-β/γ

被引：43

作者：

Shih, Ching-Yu ^{[2
]}

Chou, Tz-Chong ^{[1
]}

机构：

[1] Natl Def Med Ctr, Dept Biomed Engn, Dept Physiol, Taipei, Taiwan

[2] Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan

来源：

BIOCHEMICAL PHARMACOLOGY | 2012年 / 84卷 / 06期

关键词：

Magnolol; Peroxisome proliferator-activated receptors (PPARs); Platelet aggregation; Cyclic GMP; Protein kinase C alpha; Nitric oxide; PLATELET-AGGREGATION; NITRIC-OXIDE; ANTITHROMBOTIC AGENT; INHIBITION; CGMP;

D O I：

10.1016/j.bcp.2012.06.022

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Activation of peroxisome proliferator-activated receptor (PPAR) isoforms (alpha, beta/delta, and gamma) is known to inhibit platelet aggregation. In the present study, we examined whether PPARs-mediated pathways contribute to the antiplatelet activity of magnolol, a compound purified from Magnolia officinalis. Magnolol (20-60 mu M) dose-dependently enhanced the activity and intracellular level of PPAR-beta/gamma in platelets. In the presence of selective PPAR-beta antagonist (GSK0660) or PPAR-gamma antagonist (GW9662), the inhibition of magnolol on collagen-induced platelet aggregation and intracellular Ca2+ mobilization was significantly reversed. Moreover, magnolol-mediated up-regulation of NO/cyclic GMP/PKG pathway and Akt phosphorylation leading to increase of eNOS activity were markedly abolished by blocking PPAR-beta/gamma activity. Additionally, magnolol significantly inhibited collagen-induced PKC alpha activation through a PPAR-beta/gamma and PKC alpha interaction manner. The arachidonic acid (AA) or collagen-induced thromboxane B-2 formation and elevation of COX-1 activity caused by AA were also markedly attenuated by magnolol. However, these above effects of magnolol on platelet responses were strongly reduced by simultaneous addition of GSK0660 or GW9662, suggesting that PPAR-beta/gamma-mediated processes may account for magnolol-regulated antiplatelet mechanisms. Similarly, administration of PPAR-beta/gamma antagonists remarkably abolished the actions of magnolol in preventing platelet plug formation and prolonging bleeding time in mice. Taken together, we demonstrate for the first time that the antiplatelet and anti-thrombotic activities of magnolol are modulated by up-regulation of PPAR-beta/gamma-dependent pathways. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：793 / 803

页数：11

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