Alkamides from Echinacea angustifolia Interact with P-Glycoprotein of Primary Brain Capillary Endothelial Cells Isolated from Porcine Brain Blood Vessels

Abstract The blood-brain barrier prevents the passage of toxic compounds from blood circulation into brain tissue. Unfortunately, drugs for the treatment of neurodegenerative diseases, brain tumors, and other diseases also do not cross the blood-brain barrier. In the present investigation, we used isolated porcine brain capillary endothelial cells and a flow cytometric calcein-AM assay to analyze inhibition of P-glycoprotein, a major constituent of the blood-brain barrier. We tested 8 alkamides isolated from Echinacea angustifolia and found that four of them inhibited P-glycoprotein-mediated calcein transport in porcine brain capillary endothelial cells.

[1]  R. Bauer,et al.  Echinacea for preventing and treating the common cold. , 2014, The Cochrane database of systematic reviews.

[2]  Zhe-Sheng Chen,et al.  Revisiting the ABCs of multidrug resistance in cancer chemotherapy. , 2011, Current pharmaceutical biotechnology.

[3]  R. Bauer,et al.  Inhibition of P-glycoprotein at the blood-brain barrier by phytochemicals derived from traditional Chinese medicine. , 2009, Cancer genomics & proteomics.

[4]  O. G. Nilsen,et al.  Echinacea purpurea and P‐glycoprotein drug transport in Caco‐2 cells , 2009, Phytotherapy research : PTR.

[5]  D. K. Williams,et al.  Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics. , 2008, Molecular nutrition & food research.

[6]  Nadia Romiti1,et al.  P-Glycoprotein Inhibitory Activity of Lipophilic Constituents of Echinacea pallida Roots in a Human Proximal Tubular Cell Line , 2008, Planta medica.

[7]  R. Bauer,et al.  Cytotoxicity and p-glycoprotein modulating effects of quinolones and indoloquinazolines from the Chinese herb Evodia rutaecarpa. , 2007, Planta medica.

[8]  R. Bauer,et al.  In vitro cytotoxicity and P-glycoprotein modulating effects of geranylated furocoumarins from Tetradium daniellii. , 2007, Planta medica.

[9]  C. White,et al.  Evaluation of echinacea for the prevention and treatment of the common cold: a meta-analysis , 2007, The Lancet Infectious Diseases.

[10]  R. Bauer,et al.  The Role of Alkamides as an Active Principle of Echinacea , 2007, Planta medica.

[11]  R. Abagyan,et al.  Self-assembling cannabinomimetics: supramolecular structures of N-alkyl amides. , 2007, Journal of natural products.

[12]  J. Polli,et al.  IN VITRO P-GLYCOPROTEIN INHIBITION ASSAYS FOR ASSESSMENT OF CLINICAL DRUG INTERACTION POTENTIAL OF NEW DRUG CANDIDATES: A RECOMMENDATION FOR PROBE SUBSTRATES , 2006, Drug Metabolism and Disposition.

[13]  R. Bauer,et al.  Bioavailability and Pharmacokinetics of Alkamides From the Roots of Echinacea angustifolia in Humans , 2005, Journal of clinical pharmacology.

[14]  Thomas J. Caruso,et al.  Treatment of the common cold with echinacea: a structured review. , 2005, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[15]  E. Basch,et al.  An Evidence-Based Systematic Review of Echinacea (E. angustifolia DC, E. pallida, E. purpurea) by the Natural Standard Research Collaboration , 2005 .

[16]  M. Nedergaard,et al.  The blood–brain barrier: an overview Structure, regulation, and clinical implications , 2004, Neurobiology of Disease.

[17]  D. Clarke,et al.  Val133 and Cys137 in Transmembrane Segment 2 Are Close to Arg935 and Gly939 in Transmembrane Segment 11 of Human P-glycoprotein* , 2004, Journal of Biological Chemistry.

[18]  G. Fricker,et al.  Compound Profiling for P-Glycoprotein at the Blood–Brain Barrier Using a Microplate Screening System , 2003, Pharmaceutical Research.

[19]  A. Schinkel,et al.  Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. , 2003, Advanced drug delivery reviews.

[20]  W. Pardridge,et al.  CNS Drug Design Based on Principles of Blood‐Brain Barrier Transport , 1998, Journal of neurochemistry.

[21]  J. Drewe,et al.  Evidence for P‐glycoprotein‐modulated penetration of morphine‐6‐glucuronide into brain capillary endothelium , 1996, British journal of pharmacology.

[22]  F. Loor,et al.  Ranking of P-glycoprotein substrates and inhibitors by a calcein-AM fluorometry screening assay. , 1996, Anti-cancer drugs.

[23]  H. Pollard,et al.  Doxorubicin resistance in P388 leukemia—evidence for reduced drug influx , 1989, International journal of cancer.

[24]  E. Basch,et al.  An evidence-based systemic review Echinacea E. angustifolia DC, E. pallida, E. purpurea by the Natural Standard Research Collaboration. , 2005, Journal of herbal pharmacotherapy.

[25]  D. Schrenk,et al.  Evaluation of a vincristine resistant Caco-2 cell line for use in a calcein AM extrusion screening assay for P-glycoprotein interaction. , 2001, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[26]  R. Bauer,et al.  Echinacea for preventing and treating the common cold. , 2000, The Cochrane database of systematic reviews.

[27]  Hitoshi Sato,et al.  Dose-dependent brain penetration of SDZ PSC 833, a novel multidrug resistance-reversing cyclosporin, in rats , 1996, Cancer Chemotherapy and Pharmacology.

[28]  R. Bauer,et al.  Alkamides from the roots of Echinacea angustifolia , 1989 .