Platelet aggregation inhibitor from Murraya euchrestifolia

Abstract

Twenty-three carbazole alkaloids, murrayafoline-A (1), 3-methyl-carbazole (2), murrayanine (3), mukoeic acid (4), murrayazolidine (5), bicyclomahanimbine (6), murrayamine-A (10), -D (13), -E (14), -F (15), -I (16), -J (17), -K (18), -M (7), -N (19), murrayazoline (8), girinimbine (9), mahanimbine (11), (+)-mahanine (12), isomahanine (20), murrafoline-A (21), -B (22) and bismurrayafoline-A (23) and a triterpenoid, friedelin together with β-sitosterol were isolated and characterized from the leaves and root bark of M. euchrestifolia. Their structures were elucidated by spectroscopic analyses and/or direct comparison with authentic samples. The isolated carbazole alkaloids 1–12 were subjected to evaluation for antiplatelet aggregation activity and vasorelaxing effect. Most of the isolated carbazole alkaloids showed potent inhibitory, activity on rabbit platelet aggregation induced by arachidonic acid (100 μM), collagen (10 μg/mL) and PAF (2 ng/mL). Only murrayafoline-A (1) showed inhibition of tonic contraction induced by K+ (80 mM) + Ca2+ (1.9 mM). Compounds 1, 7 and 12 showed the promotion of the platelet aggregation or lysis at high dose. In contrast, they also exhibited antiplatelet aggregation activity at low concentration. This result could continue the philosophy of use in Chinese medicine, in that the dose variation in a prescription produced different, promotive or inhibitive, effects on therapy. © 1998 John Wiley & Sons, Ltd.