Modulation of in vitro platelet 5-HT release by species of Erythrina and Cymbopogon.
Extracts of Australian plants were screened to detect constituents affecting adenosine di-phosphate (ADP) induced platelet aggregation and [14C]5-hydroxytryptamine (5-HT) release. Extracts of four tested plants including, Eremophila gilesii, Erythrina vespertilio, Cymbopogon ambiguus, and Santalum acuminatum, were found to cause significant inhibition of platelet 5-HT release. Inhibition levels ranged from 56-98%, and was not due to the non-specific effects of protein binding tannins. These extracts, and those we have previously identified as being active, were examined further to determine if they affect epinephrine (EPN), arachidonic acid (A.A) or collagen stimulated platelet aggregation and 5-HT release. Among those extracts investigated, we found that both the methanolic extract of E. vespertilio and the dichloromethane (DCM) extract of C. ambiguus were most potent and caused significant inhibition of platelet activation induced by EPN, A.A and to a lesser extent by collagen. Inhibition of ADP induced platelet 5-HT release by both of these extracts, was dose-dependent, with IC50 values for E. vespertilio and C. ambiguus estimated to be 20.4 microl (1.855 mg/ml) and 8.34 microl (0.758 mg/ml), respectively. Overall, C. ambiguus exhibited most activity and also caused dose-dependent inhibition of A.A induced platelet activation. These results indicate that inhibition may occur specifically at a site within the A.A pathway, and suggest the presence of a cyclo-oxygenase inhibitor. Both E. vespertilio and C. ambiguus are reported to be traditional headache treatments, with the present study providing evidence that they affect 5-HT release.
Rogers
K L
KL
Genomics Research Centre and School of Health Science, Griffith University, Gold Coast, Queensland, Australia.
Grice
I D
ID
Griffiths
L R
LR
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D004895:Erythrina; D006801:Humans; D007700:Kinetics; D000432:Methanol / Q000737:chemistry; D008752:Methylene Chloride / Q000737:chemistry; D008881:Migraine Disorders / Q000188:drug therapy*; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D010974:Platelet Aggregation / Q000187:drug effects; D012701:Serotonin / Q000096:biosynthesis*
D010936:Plant Extracts; D016718:Arachidonic Acid; D012701:Serotonin; D008752:Methylene Chloride; D000244:Adenosine Diphosphate; D003094:Collagen; D000432:Methanol; D004837:Epinephrine