Inhibition of leukotriene and platelet activating factor synthesis in leukocytes by the sesquiterpene lactone scandenolide.
The sesquiterpene lactone scandenolide, isolated from the Philippines medicinal plant Mikania cordata, at a dose of 100 microM completely inhibited whole blood chemiluminescence in response to the activators PMA and zymosan. In isolated inflammatory rat leukocytes this compound inhibited both leukotriene B4 and 5-HETE production with IC50 of 15 microM and 30 microM, respectively. The formation of the cyclooxygenase product thromboxane B2 was not inhibited in the concentration range 10 to 200 microM of scandenolide. The formation of the potent inflammatory mediator platelet activating factor (PAF) was suppressed by microM concentrations of scandenolide with an IC50 of less than 20 microM. The presence of a compound in M. cordata which inhibits some of the inflammatory mediators such as leukotrienes and PAF may explain at least in part some of its medicinal properties.
Ysrael
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MC
Research Centre for Natural Sciences, University of Santo Tomas, Manila, Philippines.
Croft
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KD
D000818:Animals; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D066298:In Vitro Techniques; D007783:Lactones / Q000302:isolation & purification / Q000494:pharmacology*; D007975:Leukotriene B4 / Q000096:biosynthesis*; D010946:Plants, Medicinal / Q000032:analysis*; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D051381:Rats; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis
D006893:Hydroxyeicosatetraenoic Acids; D007783:Lactones; D010972:Platelet Activating Factor; D012717:Sesquiterpenes; D007975:Leukotriene B4; C065142:scandenolide; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D013929:Thromboxane B2