Antiplatelet effects of piplartine, an alkamide isolated from Piper tuberculatum: possible involvement of cyclooxygenase blockade and antioxidant activity

J Pharm Pharmacol. 2009 Apr;61(4):511-5. doi: 10.1211/jpp/61.04.0014.

Abstract

Objectives: Piplartine (piperlongumine; 5,6-dihydro-1-[1-oxo-3-(3,4,5-trimethoxyphenyl]-2(1H) pyridinone) is an alkaloid amide isolated from Piper species (Piperaceae). It has been reported to show multiple pharmacological activities in vitro and in vivo.

Methods: We evaluated the in-vitro antiplatelet effect of piplartine isolated from the roots of P. tuberculatum, on human platelet aggregation induced in platelet-rich plasma by the agonists collagen, adenosine 5'-diphosphate (ADP), arachidonic acid (AA) and thrombin.

Key findings: Piplartine (100 mug/ml) caused a 30% inhibition in platelet aggregation when collagen was the agonist. At 200 mug/ml, piplartine significantly inhibited the aggregation induced by arachidonic acid (100%), collagen (59%) or ADP (52%) but not that induced by thrombin. The highest concentration of piplartine (300 mug/ml) inhibited thrombin- (37%), ADP- (71%) and collagen- (98%) induced aggregation. The inhibitory effect of piplartine on ADP-induced platelet aggregation was not modified by pretreatment with pentoxifylline (a phosphodiesterase inhibitor), L-arginine (a substrate for nitric oxide synthase) or ticlopidine (a P2Y(12) purinoceptor antagonist). However, aspirin, a well-known inhibitor of cyclooxygenase, greatly increased the inhibitory effect of piplartine on arachidonic-acid-induced platelet aggregation.

Conclusions: The mechanism underlying the piplartine antiplatelet action is not totally clarified. It could be related to the inhibition of cyclooxgenase activity and a decrease in thromboxane A(2) formation, similar to that occurring with aspirin. This and other possible mechanisms require further study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / pharmacology
  • Antioxidants / pharmacology*
  • Arachidonic Acid / pharmacology
  • Collagen / pharmacology
  • Cyclooxygenase Inhibitors / pharmacology*
  • Drug Interactions
  • Humans
  • In Vitro Techniques
  • Piperaceae / chemistry*
  • Piperidones / pharmacology*
  • Plant Roots / chemistry
  • Platelet Aggregation / drug effects*
  • Platelet-Rich Plasma
  • Thrombin / pharmacology

Substances

  • Antioxidants
  • Cyclooxygenase Inhibitors
  • Piperidones
  • piplartine
  • Arachidonic Acid
  • Adenosine Diphosphate
  • Collagen
  • Thrombin