Planta Med 2007; 73(4): 330-335
DOI: 10.1055/s-2007-967137
Original Paper
Pharmacology
© Georg Thieme Verlag KG Stuttgart · New York

Transport of Decursin and Decursinol Angelate across Caco-2 and MDR-MDCK Cell Monolayers: In vitro Models for Intestinal and Blood-Brain Barrier Permeability

Vamsi L. M. Madgula1 , Bharathi Avula1 , Niranjan V. L. Reddy1 , Ikhlas A. Khan1 , 2 , Shabana I. Khan1
  • 1National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS, USA
  • 2Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, MS, USA
Further Information

Publication History

Received: November 8, 2006

Accepted: February 11, 2007

Publication Date:
19 March 2007 (online)

Abstract

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 - 12.0 × 10 - 6 cm/sec and 7.2 - 11.7 × 10 - 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 - 5.0 × 10 - 6 in Caco-2 and 6.0 - 8.0 × 10 - 6 cm/sec in MDR-MDCK monolayers, confirming that the monolayer integrity was intact at the end of the experiment.

Abbreviations

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

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Shabana I. Khan

National Center for Natural Products Research

School of Pharmacy

The University of Mississippi

University

MS 38677

USA

Phone: +01-662-915-1041

Fax: +01-662-915-7062

Email: skhan@olemiss.edu