Planta Med 2008; 74(10): 1240-1245
DOI: 10.1055/s-2008-1074560
Pharmacology
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Involvement of p38 MAPK Phosphorylation and Nitrate Formation in Aristolochic Acid-Mediated Antiplatelet Activity

Ming-Yi Shen1 , Chien-Liang Liu3 , Geroge Hsiao2 , Chiung-Yueh Liu1 , Kuang-Hung Lin1 , Duen-Suey Chou2 , Joen-Rong Sheu1 , 2
  • 1Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan
  • 2Department of Pharmacology, Taipei Medical University, Taipei, Taiwan
  • 3Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan
Further Information

Publication History

Received: September 27, 2007 Revised: May 2, 2008

Accepted: May 6, 2008

Publication Date:
18 June 2008 (online)

Abstract

Aristolochic acid (AsA) is produced from Aristolochia fangchi, and has been used as a Chinese herbal medicine. AsA possesses various biological activities including antiplatelet, antifungal, and anti-inflammatory properties. The aim of this study was to examine the mechanisms of AsA in inhibiting platelet aggregation. AsA (75 – 150 μM) exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen (1 μg/mL) than other agonists. AsA (115 and 150 μM)  inhibited collagen-induced platelet activation accompanied by [Ca+ 2]i mobilization, thromboxane A2 (TxA2) formation and phosphoinositide breakdown. On the other hand, AsA also markedly increased levels of NO/cyclic GMP, and cyclic GMP-induced vasodilator-stimulated phosphoprotein phosphorylation. AsA inhibited p38 MAPK but not ERK1/2 phosphorylation in washed platelets. In conclusion, the most important findings of this study suggest that the inhibitory effects of AsA possibly involve the (1) inhibition of the p38 MAPK-cytosolic phospholipase A2-arachidonic acid-TxA2-[Ca+ 2]i cascade, and (2) activation of NO/cyclic GMP, resulting in inhibition of phospholipase C. These results imply that Aristolochia fangchi treatment alone or in combination with other antiplatelet drugs, may result in alteration of hemostasis in vivo.

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Dr. Joen-Rong Sheu

Graduate Institute of Medical Sciences

Taipei Medical University

250 Wu-Hsing Street

Taipei 110

Taiwan

R.O.C.

Phone: +886/2/2736/1661 ext 3199

Fax: +886/2/2739/0450

Email: sheujr@tmu.edu.tw