Decursin (DE) and decursinol angelate (DA) were isolated from the roots of Angelica gigas (Apiaceae) and purified by HPLC. DE and DA have been reported to exhibit significant neuropharmacological activities, but their intestinal transport and permeability in terms of CNS penetration across the blood-brain barrier (BBB) are unknown. This study was undertaken to evaluate the IN VITRO intestinal and BBB transport of DE and DA using Caco-2 and MDR-MDCK cell monolayer models, respectively. The bidirectional transport of DE and DA across Caco-2 and MDR-MDCK monolayers was examined for 2 hours. Integrity of the monolayer was determined by TEER value and by monitoring the transport of Lucifer yellow (Ly) across the monolayers. Quantitation of DE and DA was performed by HPLC. DE and DA exhibited bidirectional transport with a Papp value in the range of 9.0-12.0x10(-6) cm/sec and 7.2-11.7x10(-6) cm/sec in Caco-2 and MDR-MDCK monolayers, respectively. The TEER values were in the range of 410-440 and 1170-1230 ohm cm2 for Caco-2 and MDR-MDCK monolayers, respectively. Ly measurement, the fluorescent marker of passive paracellular diffusion, resulted in Papp values of 2.5-5.0x10(-6) in Caco-2 and 6.0-8.0x10(-6) cm/sec in MDR-MDCK monolayers, confirming that the monolayer integrity was intact at the end of the experiment. Caco-2:human colonic adenocarcinoma DA:decursinol angelate DE:decursin Ly:Lucifer yellow MDCK:Madin-Darby canine kidney MDR:multidrug resistant Papp:apparent permeability TEER:transepithelial electrical resistance.