Involvement of p38 MAPK phosphorylation and nitrate formation in aristolochic acid-mediated antiplatelet activity

Ming Yi Shen, Chien Liang Liu, Geroge Hsiao, Chiung Yueh Liu, Kuang Hung Lin, Duen Suey Chou, Joen Rong Sheu

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1240-1245
Number of pages6
JournalPlanta Medica
Volume74
Issue number10
DOIs
Publication statusPublished - Aug 2008

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Keywords

  • Aristolochia fangchi
  • Aristolochiaceae
  • Aristolochic acid
  • Nitrate
  • p38 MAPK
  • Phospholipase C
  • Platelet aggregation

ASJC Scopus subject areas

  • Plant Science
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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