Antiplatelet effects of piplartine, an alkamide isolated from Piper tuberculatum: possible involvement of cyclooxygenase blockade and antioxidant activity.
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.
Fontenele
Juvenia B
JB
Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil.
Leal
L Kalyne A M
LK
Silveira
Edilberto R
ER
Felix
F Helder
FH
Bezerra Felipe
Cícero F
CF
Viana
Glauce S B
GS
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
D000975:Antioxidants; D016861:Cyclooxygenase Inhibitors; D010881:Piperidones; C498077:piperlongumine; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D003094:Collagen; D013917:Thrombin