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  • Title: Antiplatelet effects of piplartine, an alkamide isolated from Piper tuberculatum: possible involvement of cyclooxygenase blockade and antioxidant activity.
    Author: Fontenele JB, Leal LK, Silveira ER, Felix FH, Bezerra Felipe CF, Viana GS.
    Journal: J Pharm Pharmacol; 2009 Apr; 61(4):511-5. PubMed ID: 19298699.
    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.
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