Herbal supplements are generally considered safe; however, drug disposition is influenced by the interactions of herbal supplements and food constituents with transport and metabolic processes. Although the interference of herbal supplements with drug metabolism has been studied extensively, knowledge of how they interact with the drug transport processes is less advanced. Therefore, we describe here specific examples of experimental and human interaction studies of herbal supplement components with drug transporters addressing, for example, organic anion transporting polypeptides or P-glycoprotein, as such interactions may lead to severe side effects and altered drug efficacy. Hence, it is clearly necessary to increase the awareness of the clinical relevance of the interference of herbal supplements with the drug transport processes.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. de Lima Toccafondo Vieira M, Huang SM. 1.  2012. Botanical-drug interactions: a scientific perspective. Planta Med 78:1400–15 [Google Scholar]
  2. Calitz C, du Plessis L, Gouws C, Steyn D, Steenekamp J. 2.  et al. 2015. Herbal hepatotoxicity: current status, examples, and challenges. Exp. Opin. Drug Metab. Toxicol. 11:1551–65 [Google Scholar]
  3. Stickel F, Shouval D. 3.  2015. Hepatotoxicity of herbal and dietary supplements: an update. Arch. Toxicol. 89:851–65 [Google Scholar]
  4. Domitrovic R, Potocnjak I. 4.  2016. A comprehensive overview of hepatoprotective natural compounds: mechanism of action and clinical perspectives. Arch. Toxicol. 90:39–79 [Google Scholar]
  5. Li Y, Paxton JW. 5.  2013. The effects of flavonoids on the ABC transporters: consequences for the pharmacokinetics of substrate drugs. Exp. Opin. Drug Metab. Toxicol. 9:267–85 [Google Scholar]
  6. Haefeli WE, Carls A. 6.  2014. Drug interactions with phytotherapeutics in oncology. Exp. Opin. Drug Metab. Toxicol. 10:359–77 [Google Scholar]
  7. Palacin M, Estevez R, Bertran J, Zorzano A. 7.  1998. Molecular biology of mammalian plasma membrane amino acid transporters. Physiol. Rev. 78:969–1054 [Google Scholar]
  8. Poncet N, Taylor PM. 8.  2013. The role of amino acid transporters in nutrition. Curr. Opin. Clin. Nutr. Metab. Care 16:57–65 [Google Scholar]
  9. Wright EM. 9.  2013. Glucose transport families SLC5 and SLC50. Mol. Asp. Med. 34:183–96 [Google Scholar]
  10. Mueckler M, Thorens B. 10.  2013. The SLC2 (GLUT) family of membrane transporters. Mol. Asp. Med. 34:121–38 [Google Scholar]
  11. Hussain MM. 11.  2014. Intestinal lipid absorption and lipoprotein formation. Curr. Opin. Lipidol. 25:200–6 [Google Scholar]
  12. Rui L. 12.  2014. Energy metabolism in the liver. Compr. Physiol. 4:177–97 [Google Scholar]
  13. Voigt V, Laug L, Zebisch K, Thondorf I, Markwardt F, Brandsch M. 13.  2013. Transport of the areca nut alkaloid arecaidine by the human proton-coupled amino acid transporter 1 (hPAT1). J. Pharm. Pharmacol. 65:582–90 [Google Scholar]
  14. Tenore GC, Daglia M, Ciampaglia R, Novellino E. 14.  2015. Exploring the nutraceutical potential of polyphenols from black, green and white tea infusions—an overview. Curr. Pharm. Biotechnol. 16:265–71 [Google Scholar]
  15. Zhang Y, Hays A, Noblett A, Thapa M, Hua DH, Hagenbuch B. 15.  2013. Transport by OATP1B1 and OATP1B3 enhances the cytotoxicity of epigallocatechin 3-O-gallate and several quercetin derivatives. J. Nat. Prod. 76:368–73 [Google Scholar]
  16. Riha J, Brenner S, Böhmdorfer M, Giessrigl B, Pignitter M. 16.  et al. 2014. Resveratrol and its major sulfated conjugates are substrates of organic anion transporting polypeptides (OATPs): impact on growth of ZR-75-1 breast cancer cells. Mol. Nutr. Food Res. 58:1830–42 [Google Scholar]
  17. Stieger B, Meier PJ. 17.  2011. Pharmacogenetics of drug transporters in the enterohepatic circulation. Pharmacogenomics 12:611–31 [Google Scholar]
  18. Seeff LB, Bonkovsky HL, Navarro VJ, Wang G. 18.  2015. Herbal products and the liver: a review of adverse effects and mechanisms. Gastroenterology 148:517–32 [Google Scholar]
  19. Krämer R. 19.  1994. Functional principles of solute transport systems: concepts and perspectives. Biochim. Biophys. Acta 1185:1–34 [Google Scholar]
  20. Kobayashi D, Nozawa T, Imai K, Nezu J, Tsuji A, Tamai I. 20.  2003. Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane. J. Pharmacol. Exper. Ther. 306:703–8 [Google Scholar]
  21. Govindarajan R, Bakken AH, Hudkins KL, Lai Y, Casado FJ. 21.  et al. 2007. In situ hybridization and immunolocalization of concentrative and equilibrative nucleoside transporters in the human intestine, liver, kidneys, and placenta. Am. J. Physiol. 293:R1809–22 [Google Scholar]
  22. Groneberg DA, Döring F, Eynott PR, Fischer A, Daniel H. 22.  2001. Intestinal peptide transport: ex vivo uptake studies and localization of peptide carrier PEPT1. Am. J. Physiol. 281:G697–704 [Google Scholar]
  23. Dawson PA, Hubbert ML, Rao A. 23.  2010. Getting the mOST from OST: role of organic solute transporter, OSTα-OSTβ, in bile acid and steroid metabolism. Biochim. Biophys. Acta 1801:994–1004 [Google Scholar]
  24. Kalapos-Kovacs B, Magda B, Jani M, Fekete Z, Szabo PT. 24.  et al. 2015. Multiple ABC transporters efflux baicalin. Phytother. Res. 29:1987–90 [Google Scholar]
  25. van de Wetering K, Feddema W, Helms JB, Brouwers JF, Borst P. 25.  2009. Targeted metabolomics identifies glucuronides of dietary phytoestrogens as a major class of MRP3 substrates in vivo. Gastroenterology 137:1725–35 [Google Scholar]
  26. Li Y, Lu J, Paxton JW. 26.  2012. The role of ABC and SLC transporters in the pharmacokinetics of dietary and herbal phytochemicals and their interactions with xenobiotics. Curr. Drug Metab. 13:624–39 [Google Scholar]
  27. Planas JM, Alfaras I, Colom H, Juan ME. 27.  2012. The bioavailability and distribution of trans-resveratrol are constrained by ABC transporters. Arch. Biochem. Biophys. 527:67–73 [Google Scholar]
  28. Berger W, Micksche M, Elbling L. 28.  1997. Effects of multidrug resistance-related ATP-binding-cassette transporter proteins on the cytoskeletal activity of cytochalasins. Exp. Cell Res. 237:307–17 [Google Scholar]
  29. He SM, Li CG, Liu JP, Chan E, Duan W, Zhou SF. 29.  2010. Disposition pathways and pharmacokinetics of herbal medicines in humans. Curr. Med. Chem 17:4072–113 [Google Scholar]
  30. De Leeuw AM, Brouwer A, Knook DL. 30.  1990. Sinusoidal endothelial cells of the liver: fine structure and function in relation to age. J. Electron Microsc. Tech. 14:218–36 [Google Scholar]
  31. Burckhardt G. 31.  2012. Drug transport by organic anion transporters (OATs). Pharmacol. Ther. 136:106–30 [Google Scholar]
  32. Wlcek K, Stieger B. 32.  2014. ATP-binding cassette transporters in liver. BioFactors 40:188–98 [Google Scholar]
  33. Zhang L, Zuo Z, Lin G. 33.  2007. Intestinal and hepatic glucuronidation of flavonoids. Mol. Pharmacol. 4:833–45 [Google Scholar]
  34. Motohashi H, Inui K. 34.  2013. Multidrug and toxin extrusion family SLC47: physiological, pharmacokinetic and toxicokinetic importance of MATE1 and MATE2-K. Mol. Asp. Med. 34:661–68 [Google Scholar]
  35. Stieger B. 35.  2011. The role of the sodium-taurocholate cotransporting polypeptide (NTCP) and of the bile salt export pump (BSEP) in physiology and pathophysiology of bile formation. Handb. Exp. Pharmacol. 201:205–59 [Google Scholar]
  36. Pauli-Magnus C, Meier PJ, Stieger B. 36.  2010. Genetic determinants of drug-induced cholestasis and intrahepatic cholestasis of pregnancy. Semin. Liver Dis. 30:147–59 [Google Scholar]
  37. Saller R, Melzer J, Reichling J, Brignoli R, Meier R. 37.  2007. An updated systematic review of the pharmacology of silymarin. Forsch. Komplement. 14:70–80 [Google Scholar]
  38. Simanek V, Kren V, Ulrichova J, Vicar J, Cvak L. 38.  2000. Silymarin: What is in the name…? An appeal for a change of editorial policy. Hepatology 32:442–44 [Google Scholar]
  39. Saller R, Brignoli R, Melzer J, Meier R. 39.  2008. An updated systematic review with meta-analysis for the clinical evidence of silymarin. Forsch. Komplement. 15:9–20 [Google Scholar]
  40. Loguercio C, Festi D. 40.  2011. Silybin and the liver: from basic research to clinical practice. World J. Gastroenterol. 17:2288–301 [Google Scholar]
  41. Ganzert M, Felgenhauer N, Schuster T, Eyer F, Gourdin C, Zilker T. 41.  2008. Silibinin und Kombination von Silibinin und Penicillin im Vergleich [Amatoxin poisoning—comparison of silibinin with a combination of silibinin and penicillin]. Dtsch. Med. Wochenschr 133:2261–67 [Google Scholar]
  42. Garcia J, Costa VM, Carvalho A, Baptista P, de Pinho PG. 42.  et al. 2015. Amanita phalloides poisoning: mechanisms of toxicity and treatment. Food Chem. Toxicol. 86:41–55 [Google Scholar]
  43. Mengs U, Pohl RT, Mitchell T. 43.  2012. Legalon® SIL: the antidote of choice in patients with acute hepatotoxicity from amatoxin poisoning. Curr. Pharm. Biotechnol. 13:1964–70 [Google Scholar]
  44. Letschert K, Faulstich H, Keller D, Keppler D. 44.  2006. Molecular characterization and inhibition of amanitin uptake into human hepatocytes. Toxicol. Sci. 91:140–49 [Google Scholar]
  45. Fehrenbach T, Cui Y, Faulstich H, Keppler D. 45.  2003. Characterization of the transport of the bicyclic peptide phalloidin by human hepatic transport proteins. Naunyn Schmiedeberg's Arch. Pharmacol. 368:415–20 [Google Scholar]
  46. Meier-Abt F, Faulstich H, Hagenbuch B. 46.  2004. Identification of phalloidin uptake systems of rat and human liver. Biochim. Biophys. Acta 1664:64–69 [Google Scholar]
  47. Gundala S, Wells LD, Milliano MT, Talkad V, Luxon BA, Neuschwander-Tetri BA. 47.  2004. The hepatocellular bile acid transporter Ntcp facilitates uptake of the lethal mushroom toxin α-amanitin. Arch. Toxicol. 78:68–73 [Google Scholar]
  48. Ferenci P, Scherzer TM, Kerschner H, Rutter K, Beinhardt S. 48.  et al. 2008. Silibinin is a potent antiviral agent in patients with chronic hepatitis C not responding to pegylated interferon/ribavirin therapy. Gastroenterology 135:1561–67 [Google Scholar]
  49. Biermer M, Berg T. 49.  2009. Rapid suppression of hepatitis C viremia induced by intravenous silibinin plus ribavirin. Gastroenterology 137:390–91 [Google Scholar]
  50. Rutter K, Scherzer TM, Beinhardt S, Kerschner H, Stattermayer AF. 50.  et al. 2011. Intravenous silibinin as ‘rescue treatment’ for on-treatment non-responders to pegylated interferon/ribavirin combination therapy. Antivir. Ther. 16:1327–33 [Google Scholar]
  51. Braun DL, Rauch A, Aouri M, Durisch N, Eberhard N. 51.  et al. 2015. A lead-in with silibinin prior to triple-therapy translates into favorable treatment outcomes in difficult-to-treat HIV/hepatitis C coinfected patients. PLOS ONE 10:e0133028 [Google Scholar]
  52. Wlcek K, Koller F, Ferenci P, Stieger B. 52.  2013. Hepatocellular organic anion-transporting polypeptides (OATPs) and multidrug resistance-associated protein 2 (MRP2) are inhibited by silibinin. Drug Metab. Disp. 41:1522–28 [Google Scholar]
  53. Stieger B, Heger M, de Graaf W, Paumgartner G, van Gulik T. 53.  2012. The emerging role of transport systems in liver function tests. Eur. J. Pharmacol. 675:1–5 [Google Scholar]
  54. Tomé-Carneiro J, Larrosa M, Yáñez-Gascón MJ, Dávalos A, Gil-Zamorano J. 54.  et al. 2013. One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol. Res. 72:69–82 [Google Scholar]
  55. Maier-Salamon A, Böhmdorfer M, Thalhammer T, Szekeres T, Jaeger W. 55.  2011. Hepatic glucuronidation of resveratrol: interspecies comparison of enzyme kinetic profiles in human, mouse, rat, and dog. Drug Metab. Pharmacokinet. 26:364–73 [Google Scholar]
  56. Urpí-Sardà M, Jáuregui O, Lamuela-Raventós RM, Jaeger W, Miksits M. 56.  et al. 2005. Uptake of diet resveratrol into the human low-density lipoprotein. Identification and quantification of resveratrol metabolites by liquid chromatography coupled with tandem mass spectrometry. Anal. Chem. 77:3149–55 [Google Scholar]
  57. Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK. 57.  2004. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab. Disp. 32:1377–82 [Google Scholar]
  58. van de Wetering K, Burkon A, Feddema W, Bot A, de Jonge H. 58.  et al. 2009. Intestinal breast cancer resistance protein (BCRP)/Bcrp1 and multidrug resistance protein 3 (MRP3)/Mrp3 are involved in the pharmacokinetics of resveratrol. Mol. Pharmacol. 75:876–85 [Google Scholar]
  59. Henry C, Vitrac X, Decendit A, Ennamany R, Krisa S, Merillon JM. 59.  2005. Cellular uptake and efflux of trans-piceid and its aglycone trans-resveratrol on the apical membrane of human intestinal Caco-2 cells. J. Agric. Food Chem 53:798–803 [Google Scholar]
  60. Al-Abd AM, Mahmoud AM, El-Sherbiny GA, El-Moselhy MA, Nofal SM. 60.  et al. 2011. Resveratrol enhances the cytotoxic profile of docetaxel and doxorubicin in solid tumour cell lines in vitro. Cell Prolif 44:591–601 [Google Scholar]
  61. Jia Y, Liu Z, Huo X, Wang C, Meng Q. 61.  et al. 2015. Enhancement effect of resveratrol on the intestinal absorption of bestatin by regulating PEPT1, MDR1 and MRP2 in vivo and in vitro. Int. J. Pharm. 495:588–98 [Google Scholar]
  62. Zhu Y, He W, Gao X, Li B, Mei C. 62.  et al. 2015. Resveratrol overcomes gefitinib resistance by increasing the intracellular gefitinib concentration and triggering apoptosis, autophagy and senescence in PC9/G NSCLC cells. Sci. Rep. 5:17730 [Google Scholar]
  63. Patel KR, Brown VA, Jones DJ, Britton RG, Hemingway D. 63.  et al. 2010. Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients. Cancer Res 70:7392–99 [Google Scholar]
  64. Burkon A, Somoza V. 64.  2008. Quantification of free and protein-bound trans-resveratrol metabolites and identification of trans-resveratrol-C/O-conjugated diglucuronides – two novel resveratrol metabolites in human plasma. Mol. Nutr. Food Res 52:549–57 [Google Scholar]
  65. Chow HH, Garland LL, Hsu CH, Vining DR, Chew WM. 65.  et al. 2010. Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. Cancer Prev. Res. 3:1168–75 [Google Scholar]
  66. Bailey DG, Spence JD, Munoz C, Arnold JM. 66.  1991. Interaction of citrus juices with felodipine and nifedipine. Lancet 337:268–69 [Google Scholar]
  67. Hanley MJ, Cancalon P, Widmer WW, Greenblatt DJ. 67.  2011. The effect of grapefruit juice on drug disposition. Exp. Opin. Drug Metab. Toxicol. 7:267–86 [Google Scholar]
  68. Seden K, Dickinson L, Khoo S, Back D. 68.  2010. Grapefruit-drug interactions. Drugs 70:2373–407 [Google Scholar]
  69. Takanaga H, Ohnishi A, Matsuo H, Sawada Y. 69.  1998. Inhibition of vinblastine efflux mediated by P-glycoprotein by grapefruit juice components in Caco-2 cells. Biol. Pharm. Bull. 21:1062–66 [Google Scholar]
  70. de Castro WV, Mertens-Talcott S, Derendorf H, Butterweck V. 70.  2007. Grapefruit juice–drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells. J. Pharm. Sci. 96:2808–17 [Google Scholar]
  71. Soldner A, Christians U, Susanto M, Wacher VJ, Silverman JA, Benet LZ. 71.  1999. Grapefruit juice activates P-glycoprotein-mediated drug transport. Pharm. Res. 16:478–85 [Google Scholar]
  72. Panchagnula R, Bansal T, Varma MV, Kaul CL. 72.  2005. Co-treatment with grapefruit juice inhibits while chronic administration activates intestinal P-glycoprotein-mediated drug efflux. Pharmazie 60:922–27 [Google Scholar]
  73. Parker RB, Yates CR, Soberman JE, Laizure SC. 73.  2003. Effects of grapefruit juice on intestinal P-glycoprotein: evaluation using digoxin in humans. Pharmacotherapy 23:979–87 [Google Scholar]
  74. Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH. 74.  et al. 1997. Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. J. Clin. Investig. 99:2545–53 [Google Scholar]
  75. Dresser GK, Bailey DG, Leake BF, Schwarz UI, Dawson PA. 75.  et al. 2002. Fruit juices inhibit organic anion transporting polypeptide–mediated drug uptake to decrease the oral availability of fexofenadine. Clin. Pharmacol. Ther. 71:11–20 [Google Scholar]
  76. Lilja JJ, Backman JT, Laitila J, Luurila H, Neuvonen PJ. 76.  2003. Itraconazole increases but grapefruit juice greatly decreases plasma concentrations of celiprolol. Clin. Pharmacol. Ther. 73:192–98 [Google Scholar]
  77. An G, Mukker JK, Derendorf H, Frye RF. 77.  2015. Enzyme- and transporter-mediated beverage-drug interactions: an update on fruit juices and green tea. J. Clin. Pharmacol. 55:1313–31 [Google Scholar]
  78. Shirasaka Y, Suzuki K, Nakanishi T, Tamai I. 78.  2011. Differential effect of grapefruit juice on intestinal absorption of statins due to inhibition of organic anion transporting polypeptide and/or P-glycoprotein. J. Pharm. Sci. 100:3843–53 [Google Scholar]
  79. Mitsunaga Y, Takanaga H, Matsuo H, Naito M, Tsuruo T. 79.  et al. 2000. Effect of bioflavonoids on vincristine transport across blood-brain barrier. Eur. J. Pharmacol. 395:193–201 [Google Scholar]
  80. Honda Y, Ushigome F, Koyabu N, Morimoto S, Shoyama Y. 80.  et al. 2004. Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux. Br. J. Pharmacol. 143:856–64 [Google Scholar]
  81. Malhotra S, Bailey DG, Paine MF, Watkins PB. 81.  2001. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Clin. Pharmacol. Ther. 69:14–23 [Google Scholar]
  82. Shirasaka Y, Shichiri M, Mori T, Nakanishi T, Tamai I. 82.  2013. Major active components in grapefruit, orange, and apple juices responsible for OATP2B1-mediated drug interactions. J. Pharm. Sci. 102:3418–26 [Google Scholar]
  83. Shirasaka Y, Shichiri M, Murata Y, Mori T, Nakanishi T, Tamai I. 83.  2013. Long-lasting inhibitory effect of apple and orange juices, but not grapefruit juice, on OATP2B1-mediated drug absorption. Drug Metab. Disp. 41:615–21 [Google Scholar]
  84. Dolton MJ, Roufogalis BD, McLachlan AJ. 84.  2012. Fruit juices as perpetrators of drug interactions: the role of organic anion-transporting polypeptides. Clin. Pharmacol. Ther. 92:622–30 [Google Scholar]
  85. Imanaga J, Kotegawa T, Imai H, Tsutsumi K, Yoshizato T. 85.  et al. 2011. The effects of the SLCO2B1 c.1457C>T polymorphism and apple juice on the pharmacokinetics of fexofenadine and midazolam in humans. Pharmacogenet. Genom. 21:84–93 [Google Scholar]
  86. Misaka S, Kawabe K, Onoue S, Werba JP, Giroli M. 86.  et al. 2013. Green tea extract affects the cytochrome P450 3A activity and pharmacokinetics of simvastatin in rats. Drug Metab. Pharmacokinet. 28:514–18 [Google Scholar]
  87. Chow HH, Hakim IA, Vining DR, Crowell JA, Cordova CA. 87.  et al. 2006. Effects of repeated green tea catechin administration on human cytochrome P450 activity. Cancer Epidemiol. Biomark. Prev. 15:2473–76 [Google Scholar]
  88. Kitagawa S, Nabekura T, Kamiyama S. 88.  2004. Inhibition of P-glycoprotein function by tea catechins in KB-C2 cells. J. Pharm. Pharmacol. 56:1001–5 [Google Scholar]
  89. Roth M, Timmermann BN, Hagenbuch B. 89.  2011. Interactions of green tea catechins with organic anion-transporting polypeptides. Drug Metab. Disp. 39:920–26 [Google Scholar]
  90. Misaka S, Yatabe J, Muller F, Takano K, Kawabe K. 90.  et al. 2014. Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects. Clin. Pharmacol. Ther. 95:432–38 [Google Scholar]
  91. Jäger W, Winter O, Halper B, Salamon A, Sartori M. 91.  et al. 1997. Modulation of liver canalicular transport processes by the tyrosine-kinase inhibitor genistein: implications of genistein metabolism in the rat. Hepatology 26:1467–76 [Google Scholar]
  92. Perez M, Otero JA, Barrera B, Prieto JG, Merino G, Alvarez AI. 92.  2013. Inhibition of ABCG2/BCRP transporter by soy isoflavones genistein and daidzein: effect on plasma and milk levels of danofloxacin in sheep. Vet. J. 196:203–8 [Google Scholar]
  93. Rigalli JP, Ciriaci N, Arias A, Ceballos MP, Villanueva SSM. 93.  et al. 2015. Regulation of multidrug resistance proteins by genistein in a hepatocarcinoma cell line: impact on sorafenib cytotoxicity. PLOS ONE 10:e0119502 [Google Scholar]
  94. Wang X, Wolkoff AW, Morris ME. 94.  2005. Flavonoids as a novel class of human organic anion-transporting polypeptide OATP1B1 (OATP-C) modulators. Drug Metab. Disp. 33:1666–72 [Google Scholar]
  95. Cambria-Kiely JA. 95.  2002. Effect of soy milk on warfarin efficacy. Ann. Pharmacother. 36:1893–96 [Google Scholar]
  96. Cheng TO. 96.  2004. Potential interaction between soy milk and warfarin. Am. Fam. Physician 70:1231 [Google Scholar]
  97. Srovnalova A, Svecarova M, Zapletalova MK, Anzenbacher P, Bachleda P. 97.  et al. 2014. Effects of anthocyanidins and anthocyanins on the expression and catalytic activities of CYP2A6, CYP2B6, CYP2C9, and CYP3A4 in primary human hepatocytes and human liver microsomes. J. Agric. Food Chem. 62:789–97 [Google Scholar]
  98. Szotáková B, Bártíková H, Hlaváčová J, Boušová I, Skálová L. 98.  2013. Inhibitory effect of anthocyanidins on hepatic glutathione S-transferase, UDP-glucuronosyltransferase and carbonyl reductase activities in rat and human. Xenobiotica 43:679–85 [Google Scholar]
  99. Dreiseitel A, Oosterhuis B, Vukman KV, Schreier P, Oehme A. 99.  et al. 2009. Berry anthocyanins and anthocyanidins exhibit distinct affinities for the efflux transporters BCRP and MDR1. Br. J. Pharmacol. 158:1942–50 [Google Scholar]
  100. Srinivas NR. 100.  2013. Cranberry juice ingestion and clinical drug-drug interaction potentials: review of case studies and perspectives. J. Pharm. Pharm. Sci. 16:289–303 [Google Scholar]
  101. Hamann GL, Campbell JD, George CM. 101.  2011. Warfarin-cranberry juice interaction. Ann. Pharmacother. 45:e17 [Google Scholar]
  102. Riha J, Brenner S, Srovnalova A, Klameth L, Dvorak Z. 102.  et al. 2015. Effects of anthocyans on the expression of organic anion transporting polypeptides (SLCOs/OATPs) in primary human hepatocytes. Food Funct 6:772–79 [Google Scholar]
  103. Kasper S, Caraci F, Forti B, Drago F, Aguglia E. 103.  2010. Efficacy and tolerability of Hypericum extract for the treatment of mild to moderate depression. Eur. Neuropsychopharmacol. 20:747–65 [Google Scholar]
  104. Nahrstedt A, Butterweck V. 104.  2010. Lessons learned from herbal medicinal products: the example of St. John's wort. J. Nat. Prod. 73:1015–21 [Google Scholar]
  105. Butterweck V, Schmidt M. 105.  2007. St. John's wort: role of active compounds for its mechanism of action and efficacy. Wien. Med. Wochenschr 157:356–61 [Google Scholar]
  106. Schmidt M, Butterweck V. 106.  2015. The mechanisms of action of St. John's wort: an update. Wien. Med. Wochenschr 165:229–35 [Google Scholar]
  107. Zhou S, Chan E, Pan SQ, Huang M, Lee EJ. 107.  2004. Pharmacokinetic interactions of drugs with St. John's wort. J. Psychopharmacol. 18:262–76 [Google Scholar]
  108. Russo E, Scicchitano F, Whalley BJ, Mazzitello C, Ciriaco M. 108.  et al. 2014. Hypericum perforatum: pharmacokinetic, mechanism of action, tolerability, and clinical drug–drug interactions. Phytother. Res. 28:643–55 [Google Scholar]
  109. Moore LB, Goodwin B, Jones SA, Wisely GB, Serabjit-Singh CJ. 109.  et al. 2000. St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. PNAS 97:7500–2 [Google Scholar]
  110. Obach RS. 110.  2000. Inhibition of human cytochrome P450 enzymes by constituents of St. John's wort, an herbal preparation used in the treatment of depression. J. Pharmacol. Exp. Ther. 294:88–95 [Google Scholar]
  111. Ruschitzka F, Meier PJ, Turina M, Luscher TF, Noll G. 111.  2000. Acute heart transplant rejection due to Saint John's wort. Lancet 355:548–49 [Google Scholar]
  112. Breidenbach T, Kliem V, Burg M, Radermacher J, Hoffmann MW, Klempnauer J. 112.  2000. Profound drop of cyclosporin A whole blood trough levels caused by St. John's wort (Hypericum perforatum). Transplantation 69:2229–30 [Google Scholar]
  113. Ernst E. 113.  2002. St. John's wort supplements endanger the success of organ transplantation. Arch. Surg. 137:316–19 [Google Scholar]
  114. Dürr D, Stieger B, Kullak-Ublick GA, Rentsch KM, Steinert HC. 114.  et al. 2000. St. John's wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin. Pharmacol. Ther. 68:598–604 [Google Scholar]
  115. Borrelli F, Izzo AA. 115.  2009. Herb–drug interactions with St. John's wort (Hypericum perforatum): an update on clinical observations. AAPS J 11:710–27 [Google Scholar]
  116. Rahimi R, Abdollahi M. 116.  2012. An update on the ability of St. John's wort to affect the metabolism of other drugs. Exp. Opin. Drug Metab. Toxicol. 8:691–708 [Google Scholar]
  117. Mannel M. 117.  2004. Drug interactions with St. John's wort: mechanisms and clinical implications. Drug Saf 27:773–97 [Google Scholar]
  118. Posadzki P, Watson L, Ernst E. 118.  2013. Herb–drug interactions: an overview of systematic reviews. Br. J. Clin. Pharmacol. 75:603–18 [Google Scholar]
  119. Pan SY, Litscher G, Gao SH, Zhou SF, Yu ZL. 119.  et al. 2014. Historical perspective of traditional indigenous medical practices: the current renaissance and conservation of herbal resources. Evid.-Based Complement. Altern. Med 2014:525340 [Google Scholar]
  120. Pan SY, Litscher G, Chan K, Yu ZL, Chen HQ, Ko KM. 120.  2014. Traditional medicines in the world: Where to go next?. Evid. Based Complement. Alternat. Med 2014:739895 [Google Scholar]
  121. Hong M, Li S, Tan HY, Wang N, Tsao SW, Feng Y. 121.  2015. Current status of herbal medicines in chronic liver disease therapy: the biological effects, molecular targets and future prospects. Int. J. Mol. Sci. 16:28705–45 [Google Scholar]
  122. Seeff LB, Curto TM, Szabo G, Everson GT, Bonkovsky HL. 122.  et al. 2008. Herbal product use by persons enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial. Hepatology 47:605–12 [Google Scholar]
  123. Struppler A, Rossler H. 123.  1957. Choleretic effect of artichoke extract. Med. Monatsschrift 11221–23 (in German) [Google Scholar]
  124. Kraft K. 124.  1997. Artichoke leaf extract—recent findings reflecting effects on lipid metabolism, liver and gastrointestinal tracts. Phytomedicine 4:369–78 [Google Scholar]
  125. Preziosi P, Loscalzo B. 125.  1958. Pharmacological properties of 1, 4 dicaffeylquinic acid, the active principle of Cynara scolimus. Arch. Int. Pharmacodyn. Ther. 117:63–80 [Google Scholar]
  126. Kirchhoff R, Beckers C, Kirchhoff GM, Trinczek-Gärtner H, Petrowicz O, Reimann HJ. 126.  1994. Increase in choleresis by means of artichoke extract. Phytomedicine 1:107–15 [Google Scholar]
  127. Salem MB, Affes H, Ksouda K, Dhouibi R, Sahnoun Z. 127.  et al. 2015. Pharmacological studies of artichoke leaf extract and their health benefits. Plant Foods Hum. Nutr. 70:441–53 [Google Scholar]
  128. Zhang ZY, Si DY, Yi XL, Liu CX. 128.  2014. Inhibitory effect of medicinal plant-derived carboxylic acids on the human transporters hOAT1, hOAT3, hOATP1B1, and hOATP2B1. Chin. J. Nat. Med. 12:131–38 [Google Scholar]
  129. Tang L, Li Y, Chen WY, Zeng S, Dong LN. 129.  et al. 2014. Breast cancer resistance protein-mediated efflux of luteolin glucuronides in HeLa cells overexpressing UDP-glucuronosyltransferase 1A9. Pharm. Res. 31:847–60 [Google Scholar]
  130. Liu CX, Yi XL, Si DY, Xiao XF, He X, Li YZ. 130.  2011. Herb-drug interactions involving drug metabolizing enzymes and transporters. Curr. Drug Metab. 12:835–49 [Google Scholar]
  131. Zhang A, Li Q, He X, Si D, Liu C. 131.  2015. Interactions between transporters and herbal medicines/drugs: a focus on hepatoprotective compounds. Curr. Drug Metab. 16:911–18 [Google Scholar]
  132. Nakanishi T, Tamai I. 132.  2015. Interaction of drug or food with drug transporters in intestine and liver. Curr. Drug Metab. 16:753–64 [Google Scholar]
  133. Sprouse AA, van Breemen RB. 133.  2016. Pharmacokinetic interactions between drugs and botanical dietary supplements. Drug Metab. Disp. 44:162–71 [Google Scholar]
  134. Milić N, Milosević N, Golocorbin Kon S, Bozić T, Abenavoli L, Borrelli F. 134.  2014. Warfarin interactions with medicinal herbs. Nat. Prod. Commun. 9:1211–16 [Google Scholar]
  135. Stieger B, Hagenbuch B. 135.  2014. Organic anion-transporting polypeptides. Curr. Top Membr. 73:205–32 [Google Scholar]
  136. Lin JH. 136.  1995. Species similarities and differences in pharmacokinetics. Drug Metab. Disp. 23:1008–21 [Google Scholar]
  137. Meyer UA, Zanger UM, Schwab M. 137.  2013. Omics and drug response. Annu. Rev. Pharmacol. Toxicol. 53:475–502 [Google Scholar]
  138. Gurley BJ. 138.  2012. Pharmacokinetic herb-drug interactions (part 1): origins, mechanisms, and the impact of botanical dietary supplements. Planta Med 78:1478–89 [Google Scholar]

Data & Media loading...

Supplementary Data

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error