title: Antiplatelet effects of piplartine, an alkamide isolated from Piper tuberculatum: possible involvement of cyclooxygenase blockade and antioxidant activity.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil.
authors.forename: Juvenia B
authors.initials: JB
authors.lastname: Fontenele
authors.forename: L Kalyne A M
authors.initials: LK
authors.lastname: Leal
authors.forename: Edilberto R
authors.initials: ER
authors.lastname: Silveira
authors.forename: F Helder
authors.initials: FH
authors.lastname: Felix
authors.forename: Cícero F
authors.initials: CF
authors.lastname: Bezerra Felipe
authors.forename: Glauce S B
authors.initials: GS
authors.lastname: Viana
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000494:pharmacology; D003094:Collagen / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D066298:In Vitro Techniques; D026321:Piperaceae / Q000737:chemistry*; D010881:Piperidones / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D010974:Platelet Aggregation / Q000187:drug effects*; D053657:Platelet-Rich Plasma; D013917:Thrombin / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D010881:Piperidones; C498077:piperlongumine; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; D013917:Thrombin