Berry anthocyanins and anthocyanidins exhibit distinct affinities for the efflux transporters BCRP and MDR1

British Journal of Pharmacology

Volumn 158, Issue 8, 2009, Pages 1942-1950

  Dreiseitel, A ^a   Oosterhuis, B ^b   Vukman, K V ^b,c   Schreier, P ^d   Oehme, A ^d   Locher, S ^d   Hajak, G ^a   Sand, P G ^a  

^a UNIVERSITY OF REGENSBURG   (Germany)

^b SOLVO BIOTECHNOLOGY   (Hungary)

^c DUBLIN CITY UNIVERSITY   (Ireland)

^d UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

ABC transporter; Anthocyanidin; Anthocyanin; BCRP; Flavonoid; MDR1; P glycoprotein

Indexed keywords

ADENOSINE TRIPHOSPHATASE; AGLYCONE; ANTHOCYANIDIN; ANTHOCYANIN; BREAST CANCER RESISTANCE PROTEIN; CYANIDIN 3 GALACTOSIDE; CYANIDIN 3 GLUCOSIDE; CYANIDIN 3 RUTINOSIDE; CYANIDIN 3,5 DIGLUCOSIDE; CYANIDIN CHLORIDE; DELPHINIDIN; DELPHINIDIN 3 GLUCOSIDE; DYE; FLAVONOID; MALVIDIN 3 GALACTOSIDE; MALVIDIN 3 GLUCOSIDE; MALVIDIN 3,5 DIGLUCOSE; MALVIDIN CHLORIDE; MULTIDRUG RESISTANCE PROTEIN 1; PELARGONIDIN; PELARGONIDIN 3,5 DIGLUCOSIDE; PEONIDIN; PEONIDIN 3 GLUCOSIDE; PETUNIDIN CHLORIDE; PLANT MEDICINAL PRODUCT; UNCLASSIFIED DRUG; VESICULAR TRANSPORT PROTEIN;

ANIMAL CELL; ARTICLE; BERRY; BINDING AFFINITY; BIOASSAY; BLOOD BRAIN BARRIER; BRAIN; CONTROLLED STUDY; DRUG ACTIVITY; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG INHIBITION; ENZYME ACTIVITY; ENZYME SPECIFICITY; HUMAN; HUMAN CELL; IN VITRO STUDY; LEPIDOPTERA; NONHUMAN; PLASMA; PRIORITY JOURNAL; PROTEIN INTERACTION; PROTEIN TRANSPORT;

ANTHOCYANINS; ATP-BINDING CASSETTE TRANSPORTERS; BIOLOGICAL AVAILABILITY; BIOLOGICAL TRANSPORT; BLOOD-BRAIN BARRIER; BRAIN; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG INTERACTIONS; FRUIT; HUMANS; INTESTINES; NEOPLASM PROTEINS; P-GLYCOPROTEIN;

EID: 71649106260     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2009.00495.x     Document Type: Article

References (95)

1. Adachi Y, Suzuki H, Sugiyama Y (2001). Comparative studies on in vitro methods for evaluating in vivo function of MDR1 P-glycoprotein. Pharm Res 18: 1660 1668.
2. Ahmed-Belkacem A, Pozza A, Munoz-Martinez F, Bates SE, Castanys S, Gamarro F et al. (2005). Flavonoid structure-activity studies identify 6-prenylchrysin and tectochrysin as potent and specific inhibitors of breast cancer resistance protein ABCG2. Cancer Res 65: 4852 4860.
3. Albermann N, Schmitz-Winnenthal FH, Z'Graggen K, Volk C, Hoffmann MM, Haefeli WE et al. (2005). Expression of the drug transporters MDR1/ABCB1, MRP1/ABCC1, MRP2/ABCC2, BCRP/ABCG2, and PXR in peripheral blood mononuclear cells and their relationship with the expression in intestine and liver. Biochem Pharmacol 70: 949 958.
4. Allen JD, van Loevezijn A, Lakhai JM, van der Valk M, van Tellingen O, Reid G et al. (2002). Potent and specific inhibition of the breast cancer resistance protein multidrug transporter in vitro and in mouse intestine by a novel analogue of fumitremorgin C. Mol Cancer Ther 1: 417 425.
5. Alvarez AI, Real R, Perez M, Mendoza G, Prieto JG, Merino G (2009). Modulation of the activity of ABC transporters (P-glycoprotein, MRP2, BCRP) by flavonoids and drug response. J Pharm Sci (in press).
6. Andres-Lacueva C, Shukitt-Hale B, Galli RL, Jauregui O, Lamuela-Raventos RM, Joseph JA (2005). Anthocyanins in aged blueberry-fed rats are found centrally and may enhance memory. Nutr Neurosci 8: 111 120.
7. Aronica E, Gorter JA, Redeker S, van Vliet EA, Ramkema M, Scheffer GL et al. (2005). Localization of breast cancer resistance protein (BCRP) in microvessel endothelium of human control and epileptic brain. Epilepsia 46: 849 857.
8. Begley DJ (2004). ABC transporters and the blood-brain barrier. Curr Pharm Des 10: 1295 1312.
9. Bodo A, Bakos E, Szeri F, Varadi A, Sarkadi B (2003). Differential modulation of the human liver conjugate transporters MRP2 and MRP3 by bile acids and organic anions. J Biol Chem 278: 23529 23537.
10. Brand W, van der Wel PA, Rein MJ, Barron D, Williamson G, van Bladeren PJ et al 2008). Metabolism and transport of the citrus flavonoid hesperetin in Caco-2 cell monolayers. Drug Metab Dispos 36: 1794 1802.
11. Breedveld P, Beijnen JH, Schellens JH (2006). Use of P-glycoprotein and BCRP inhibitors to improve oral bioavailability and CNS penetration of anticancer drugs. Trends Pharmacol Sci 27: 17 24.
12. Bub A, Watzl B, Heeb D, Rechkemmer G, Briviba K (2001). Malvidin-3-glucoside bioavailability in humans after ingestion of red wine, dealcoholized red wine and red grape juice. Eur J Nutr 40: 113 120.
13. Cervenak J, Andrikovics H, Ozvegy-Laczka C, Tordai A, Nemet K, Varadi A et al. (2006). The role of the human ABCG2 multidrug transporter and its variants in cancer therapy and toxicology. Cancer Lett 234: 62 72.
14. Chun OK, Chung SJ, Song WO (2007). Estimated dietary flavonoid intake and major food sources of U.S. adults. J Nutr 137: 1244 1252.
15. Conseil G, Baubichon-Cortay H, Dayan G, Jault JM, Barron D, Di Pietro A (1998). Flavonoids: a class of modulators with bifunctional interactions at vicinal ATP-and steroid-binding sites on mouse P-glycoprotein. Proc Natl Acad Sci USA 95: 9831 9836.
16. Cooray HC, Janvilisri T, van Veen HW, Hladky SB, Barrand MA (2004). Interaction of the breast cancer resistance protein with plant polyphenols. Biochem Biophys Res Commun 317: 269 275.
17. Critchfield JW, Welsh CJ, Phang JM, Yeh GC (1994). Modulation of adriamycin accumulation and efflux by flavonoids in HCT-15 colon cells. Activation of P-glycoprotein as a putative mechanism. Biochem Pharmacol 48: 1437 1445.
18. Dauchy S, Dutheil F, Weaver RJ, Chassoux F, Daumas-Duport C, Couraud PO et al. (2008). ABC transporters, cytochromes P450 and their main transcription factors: expression at the human blood-brain barrier. J Neurochem 107: 1518 1528.
19. Doyle LA, Ross DD (2003). Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene 22: 7340 7358.
20. Duffy KB, Spangler EL, Devan BD, Guo Z, Bowker JL, Janas AM et al. (2008). A blueberry-enriched diet provides cellular protection against oxidative stress and reduces a kainate-induced learning impairment in rats. Neurobiol Aging 29: 1680 1689.
21. Dupuy J, Lespine A, Sutra JF, Alvinerie M (2006). The interaction between moxidectin and MDR transporters in primary cultures of rat hepatocytes. J Vet Pharmacol Ther 29: 107 111.
22. Eisenblatter T, Huwel S, Galla HJ (2003). Characterisation of the brain multidrug resistance protein (BMDP/ABCG2/BCRP) expressed at the blood-brain barrier. Brain Res 971: 221 231.
23. El Mohsen MA, Marks J, Kuhnle G, Moore K, Debnam E, Kaila Srai S et al. (2006). Absorption, tissue distribution and excretion of pelargonidin and its metabolites following oral administration to rats. Br J Nutr 95: 51 58.
24. Felgines C, Texier O, Besson C, Fraisse D, Lamaison JL, Remesy C (2002). Blackberry anthocyanins are slightly bioavailable in rats. J Nutr 132: 1249 1253.
25. Felgines C, Talavera S, Texier O, Gil-Izquierdo A, Lamaison JL, Remesy C (2005). Blackberry anthocyanins are mainly recovered from urine as methylated and glucuronidated conjugates in humans. J Agric Food Chem 53: 7721 7727.
26. Fricker G (2008). Drug interactions with natural products at the blood brain barrier. Curr Drug Metab 9: 1018 1025.
27. Fromm MF (2003). Importance of P-glycoprotein for drug disposition in humans. Eur J Clin Invest 33: 6 9.
28. Garcia-Alonso M, Rimbach G, Sasai M, Nakahara M, Matsugo S, Uchida Y et al. (2005). Electron spin resonance spectroscopy studies on the free radical scavenging activity of wine anthocyanins and pyranoanthocyanins. Mol Nutr Food Res 49: 1112 1119.
29. Gottesman MM, Pastan I, Ambudkar SV (1996). P-glycoprotein and multidrug resistance. Curr Opin Genet Dev 6: 610 617.
30. Gupta A, Zhang Y, Unadkat JD, Mao Q (2004). HIV protease inhibitors are inhibitors but not substrates of the human breast cancer resistance protein (BCRP/ABCG2). J Pharmacol Exp Ther 310: 334 341.
31. van Herwaarden AE, Wagenaar E, Karnekamp B, Merino G, Jonker JW, Schinkel AH (2006). Breast cancer resistance protein (Bcrp1/Abcg2) reduces systemic exposure of the dietary carcinogens aflatoxin B1, IQ and Trp-P-1 but also mediates their secretion into breast milk. Carcinogenesis 27: 123 130.
32. Hilgendorf C, Ahlin G, Seithel A, Artursson P, Ungell AL, Karlsson J (2007). Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines. Drug Metab Dispos 35: 1333 1340.
33. Imai Y, Tsukahara S, Asada S, Sugimoto Y (2004). Phytoestrogens/ flavonoids reverse breast cancer resistance protein/ABCG2-mediated multidrug resistance. Cancer Res 64: 4346 4352.
34. Jonker JW, Merino G, Musters S, van Herwaarden AE, Bolscher E, Wagenaar E et al. (2005). The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk. Nat Med 11: 127 129.
35. Joseph JA, Shukitt-Hale B, Denisova NA, Bielinski D, Martin A, McEwen JJ et al. (1999). Reversals of age-related declines in neuronal signal transduction, cognitive, and motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J Neurosci 19: 8114 8121.
36. Kahle K, Kraus M, Scheppach W, Ackermann M, Ridder F, Richling E (2006). Studies on apple and blueberry fruit constituents: do the polyphenols reach the colon after ingestion? Mol Nutr Food Res 50: 418 423.
37. Kalt W, Blumberg JB, McDonald JE, Vinqvist-Tymchuk MR, Fillmore SA, Graf BA et al. (2008). Identification of anthocyanins in the liver, eye, and brain of blueberry-fed pigs. J Agric Food Chem 56: 705 712.
38. Katayama K, Masuyama K, Yoshioka S, Hasegawa H, Mitsuhashi J, Sugimoto Y (2007). Flavonoids inhibit breast cancer resistance protein-mediated drug resistance: transporter specificity and structure-activity relationship. Cancer Chemother Pharmacol 60: 789 797.
39. Kim JM, Kim JS, Yoo H, Choung MG, Sung MK (2008). Effects of black soybean [Glycine max (L.) Merr.] seed coats and its anthocyanidins on colonic inflammation and cell proliferation in vitro and in vivo. J Agric Food Chem 56: 8427 8433.
40. Kitagawa S (2006). Inhibitory effects of polyphenols on p-glycoprotein-mediated transport. Biol Pharm Bull 29: 1 6.
41. Kuhnle M, Egger M, Muller C, Mahringer A, Bernhardt G, Fricker G et al. (2009). Potent and Selective Inhibitors of Breast Cancer Resistance Protein (ABCG2) Derived from the p-Glycoprotein (ABCB1) Modulator Tariquidar. J Med Chem 52: 1190 1197.
42. Kusuhara H, Sugiyama Y (2002). Role of transporters in the tissue-selective distribution and elimination of drugs: transporters in the liver, small intestine, brain and kidney. J Control Release 78: 43 54.
43. Kusuhara H, Sugiyama Y (2007). ATP-binding cassette, subfamily G (ABCG family). Pflugers Arch 453: 735 744.
44. Lazarowski A, Czornyj L, Lubienieki F, Girardi E, Vazquez S, D'Giano C (2007). ABC transporters during epilepsy and mechanisms underlying multidrug resistance in refractory epilepsy. Epilepsia 48: 140 149.
45. Lee YJ, Kusuhara H, Jonker JW, Schinkel AH, Sugiyama Y (2005). Investigation of efflux transport of dehydroepiandrosterone sulfate and mitoxantrone at the mouse blood-brain barrier: a minor role of breast cancer resistance protein. J Pharmacol Exp Ther 312: 44 52.
46. Litman T, Brangi M, Hudson E, Fetsch P, Abati A, Ross DD et al. (2000). The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci 113: 2011 2021.
47. Loscher W, Potschka H (2005). Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx 2: 86 98.
48. McGhie TK, Walton MC (2007). The bioavailability and absorption of anthocyanins: towards a better understanding. Mol Nutr Food Res 51: 702 713.
49. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ et al. (2002). Passive permeability and P-glycoprotein- mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther 303: 1029 1037.
50. Maliepaard M, Scheffer GL, Faneyte IF, van Gastelen MA, Pijnenborg AC, Schinkel AH et al. (2001). Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer Res 61: 3458 3464.
51. Mao Q, Unadkat JD (2005). Role of the breast cancer resistance protein (ABCG2) in drug transport. AAPS J 7: E118 E133.
52. Matsumoto H, Inaba H, Kishi M, Tominaga S, Hirayama M, Tsuda T (2001). Orally administered delphinidin 3-rutinoside and cyanidin 3-rutinoside are directly absorbed in rats and humans and appear in the blood as the intact forms. J Agric Food Chem 49: 1546 1551.
53. Matsunaga N, Imai S, Inokuchi Y, Shimazawa M, Yokota S, Araki Y et al. (2009). Bilberry and its main constituents have neuroprotective effects against retinal neuronal damage in vitro and in vivo. Mol Nutr Food Res 53: 869 877.
54. Mitsunaga Y, Takanaga H, Matsuo H, Naito M, Tsuruo T, Ohtani H et al. (2000). Effect of bioflavonoids on vincristine transport across blood-brain barrier. Eur J Pharmacol 395: 193 201.
55. del Moral RG, Olmo A, Aguilar M, O'Valle F (1998). P glycoprotein: a new mechanism to control drug-induced nephrotoxicity. Exp Nephrol 6: 89 97.
56. Mullen W, Edwards CA, Serafini M, Crozier A (2008). Bioavailability of pelargonidin-3-O-glucoside and its metabolites in humans following the ingestion of strawberries with and without cream. J Agric Food Chem 56: 713 719.
57. Murkovic M, Toplak H, Adam U, Pfannhauser W (2000). Analysis of Anthocyanins in Plasma for Determination of their Bioavailability. J Food Compos Anal 13: 291 296.
58. Nabekura T, Kamiyama S, Kitagawa S (2005). Effects of dietary chemopreventive phytochemicals on P-glycoprotein function. Biochem Biophys Res Commun 327: 866 870.
59. Nakanishi T, Karp JE, Tan M, Doyle LA, Peters T, Yang W et al. (2003). Quantitative analysis of breast cancer resistance protein and cellular resistance to flavopiridol in acute leukemia patients. Clin Cancer Res 9: 3320 3328.
60. Ozvegy C, Varadi A, Sarkadi B (2002). Characterization of drug transport, ATP hydrolysis, and nucleotide trapping by the human ABCG2 multidrug transporter. Modulation of substrate specificity by a point mutation. J Biol Chem 277: 47980 47990.
61. Passamonti S, Vrhovsek U, Vanzo A, Mattivi F (2005). Fast access of some grape pigments to the brain. J Agric Food Chem 53: 7029 7034.
62. Pauli-Magnus C, Kroetz DL (2004). Functional implications of genetic polymorphisms in the multidrug resistance gene MDR1 (ABCB1). Pharm Res 21: 904 913.
63. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO et al. (2001). Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther 299: 620 628.
64. Rahman MM, Ichiyanagi T, Komiyama T, Sato S, Konishi T (2008). Effects of anthocyanins on psychological stress-induced oxidative stress and neurotransmitter status. J Agric Food Chem 56: 7545 7550.
65. Ramirez MR, Izquierdo I, do Carmo Bassols Raseira M, Zuanazzi JA, Barros D, Henriques AT (2005). Effect of lyophilised Vaccinium berries on memory, anxiety and locomotion in adult rats. Pharmacol Res 52: 457 462.
66. Robey RW, Polgar O, Deeken J, To KW, Bates SE (2007). ABCG2: determining its relevance in clinical drug resistance. Cancer Metastasis Rev 26: 39 57.
67. Salminen H, Heinonen M (2008). Plant phenolics affect oxidation of tryptophan. J Agric Food Chem 56: 7472 7481.
68. Sarkadi B, Price EM, Boucher RC, Germann UA, Scarborough GA (1992). Expression of the human multidrug resistance cDNA in insect cells generates a high activity drug-stimulated membrane ATPase. J Biol Chem 267: 4854 4858.
69. Sarkadi B, Ozvegy-Laczka C, Nemet K, Varadi A (2004). ABCG2-a transporter for all seasons. FEBS Lett 567: 116 120.
70. Satué-Gracia MT, Heinonen M, Frankel EN (1997). Anthocyanins as antioxidants on human low-density lipoprotein and lecithin-liposome systems. J Agric Food Chem 45: 3362 3367.
71. Schinkel AH, Jonker JW (2003). Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv Drug Deliv Rev 55: 3 29.
72. Shitara Y, Sato H, Sugiyama Y (2005). Evaluation of drug-drug interaction in the hepatobiliary and renal transport of drugs. Annu Rev Pharmacol Toxicol 45: 689 723.
73. Shukitt-Hale B, Carey A, Simon L, Mark DA, Joseph JA (2006). Effects of Concord grape juice on cognitive and motor deficits in aging. Nutrition 22: 295 302.
74. Shukitt-Hale B, Lau FC, Joseph JA (2008). Berry fruit supplementation and the aging brain. J Agric Food Chem 56: 636 641.
75. Siddiqui A, Kerb R, Weale ME, Brinkmann U, Smith A, Goldstein DB et al. (2003). Association of multidrug resistance in epilepsy with a polymorphism in the drug-transporter gene ABCB1. N Engl J Med 348: 1442 1448.
76. Sugimoto Y, Tsukahara S, Ishikawa E, Mitsuhashi J (2005). Breast cancer resistance protein: molecular target for anticancer drug resistance and pharmacokinetics/pharmacodynamics. Cancer Sci 96: 457 465.
77. Sun H, Dai H, Shaik N, Elmquist WF (2003). Drug efflux transporters in the CNS. Adv Drug Deliv Rev 55: 83 105.
78. Talavera S, Felgines C, Texier O, Besson C, Gil-Izquierdo A, Lamaison JL et al. (2005). Anthocyanin metabolism in rats and their distribution to digestive area, kidney, and brain. J Agric Food Chem 53: 3902 3908.
79. Tarozzi A, Morroni F, Hrelia S, Angeloni C, Marchesi A, Cantelli-Forti G et al. (2007). Neuroprotective effects of anthocyanins and their in vivo metabolites in SH-SY5Y cells. Neurosci Lett 424: 36 40.
80. Thomasset S, Berry DP, Cai H, West K, Marczylo TH, Marsden D et al. (2009). Pilot study of oral anthocyanins for colorectal cancer chemoprevention. Cancer Prev Res (Phila Pa) 2: 625 633.
81. Tsuda T, Horio F, Osawa T (1999). Absorption and metabolism of cyanidin 3-O-beta-D-glucoside in rats. FEBS Lett 449: 179 182.
82. de Vries NA, Zhao J, Kroon E, Buckle T, Beijnen JH, van Tellingen O (2007). P-glycoprotein and breast cancer resistance protein: two dominant transporters working together in limiting the brain penetration of topotecan. Clin Cancer Res 13: 6440 6449.
83. Wang EJ, Barecki-Roach M, Johnson WW (2002). Elevation of P-glycoprotein function by a catechin in green tea. Biochem Biophys Res Commun 297: 412 418.
84. Wang J, Mazza G (2002). Inhibitory effects of anthocyanins and other phenolic compounds on nitric oxide production in LPS/IFN-gamma-activated RAW 264.7 macrophages. J Agric Food Chem 50: 850 857. (Pubitemid 34163634)
85. Williams CM, El Mohsen MA, Vauzour D, Rendeiro C, Butler LT, Ellis JA et al. (2008). Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels. Free Radic Biol Med 45: 295 305.
86. Wu X, Gu L, Prior RL, McKay S (2004). Characterization of anthocyanins and proanthocyanidins in some cultivars of Ribes, Aronia, and Sambucus and their antioxidant capacity. J Agric Food Chem 52: 7846 7856.
87. Wu X, Beecher GR, Holden JM, Haytowitz DB, Gebhardt SE, Prior RL (2006). Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption. J Agric Food Chem 54: 4069 4075.
88. Xu C, Li CY, Kong AN (2005). Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharm Res 28: 249 268.
89. Yoo HH, Lee M, Chung HJ, Lee SK, Kim DH (2007). Effects of diosmin, a flavonoid glycoside in citrus fruits, on P-glycoprotein-mediated drug efflux in human intestinal Caco-2 cells. J Agric Food Chem 55: 7620 7625. (Pubitemid 47492324)
90. Youdim KA, Shukitt-Hale B, Joseph JA (2004). Flavonoids and the brain: interactions at the blood-brain barrier and their physiological effects on the central nervous system. Free Radic Biol Med 37: 1683 1693.
91. Zafra-Stone S, Yasmin T, Bagchi M, Chatterjee A, Vinson JA, Bagchi D (2007). Berry anthocyanins as novel antioxidants in human health and disease prevention. Mol Nutr Food Res 51: 675 683.
92. Zhang S, Yang X, Morris ME (2004a). Combined effects of multiple flavonoids on breast cancer resistance protein (ABCG2)-mediated transport. Pharm Res 21: 1263 1273. (Pubitemid 38954213)
93. Zhang S, Yang X, Morris ME (2004b). Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport. Mol Pharmacol 65: 1208 1216. (Pubitemid 38543491)
94. Zhao R, Raub TJ, Sawada GA, Kasper SC, Bacon JA, Bridges AS et al. (2009). Breast cancer resistance protein interacts with various compounds in vitro, but plays a minor role in substrate efflux at the blood-brain barrier. Drug Metab Dispos 37: 1251 1258.
95. Zhou S, Lim LY, Chowbay B (2004). Herbal modulation of P-glycoprotein. Drug Metab Rev 36: 57 104.