Potential drug interactions associated with glycyrrhizin and glycyrrhetinic acid

References

• Abelo A, Andersson TB, Antonsson M, et al. (2000). Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes. Drug Metab Dispos 28:966–972
   PubMed Web of Science ®Google Scholar
• Agarwal MK, Iqbal M, Athar M. (2005). Inhibitory effect of 18beta-glycyrrhetinic acid on 12-O-tetradecanoyl phorbol-13-acetate-induced cutaneous oxidative stress and tumor promotion in mice. Redox Rep 10:151–157
   PubMed Web of Science ®Google Scholar
• Akao T. (2000). Differences in the metabolism of glycyrrhizin, glycyrrhetic acid and glycyrrhetic acid monoglucuronide by human intestinal flora. Biol Pharm Bull 23:1418–1423
   PubMed Web of Science ®Google Scholar
• Akao T. (2001). Effect of pH on metabolism of glycyrrhizin, glycyrrhetic acid and glycyrrhetic acid monoglucuronide by collected human intestinal flora. Biol Pharm Bull 24:1108–1112
   PubMed Web of Science ®Google Scholar
• Akao T, Akao T, Kobashi K. (1988). Glycyrrhizin stimulates growth of Eubacterium sp. strain GLH, a human intestinal anaerobe. Appl Environ Microbiol 54:2027–2030
   PubMed Web of Science ®Google Scholar
• Akao T, Hayashi T, Kobashi K, et al. (1994). Intestinal bacterial hydrolysis is indispensable to absorption of 18 beta-glycyrrhetic acid after oral administration of glycyrrhizin in rats. J Pharm Pharmacol 46:135–137
   PubMed Web of Science ®Google Scholar
• Amagaya S, Sugishita E, Ogihara Y, et al. (1984). Comparative studies of the stereoisomers of glycyrrhetinic acid on anti-inflammatory activities. J Pharmacobiodyn 7:923–928
   PubMedGoogle Scholar
• Ao Y, Chen J, Yue J, et al. (2008). Effects of 18alpha-glycyrrhizin on the pharmacodynamics and pharmacokinetics of glibenclamide in alloxan-induced diabetic rats. Eur J Pharmacol 587:330–335
   PubMed Web of Science ®Google Scholar
• Arase Y, Ikeda K, Murashima N, et al. (1997). The long term efficacy of glycyrrhizin in chronic hepatitis C patients. Cancer 79:1494–1500
   PubMed Web of Science ®Google Scholar
• Berth-Jones J. (2005). The use of ciclosporin in psoriasis. J Dermatolog Treat 16:258–277
   PubMed Web of Science ®Google Scholar
• Caldwell SH, Crespo DM, Kang HS, et al. (2004). Obesity and hepatocellular carcinoma. Gastroenterology 127:S97–S103
   PubMed Web of Science ®Google Scholar
• Chen L, Yang J, Davey AK, et al. (2009). Effects of diammonium glycyrrhizinate on the pharmacokinetics of aconitine in rats and the potential mechanism. Xenobiotica 39:955–963
   PubMed Web of Science ®Google Scholar
• Chen S, Wang K,Wan YJ. (2010). Retinoids activate RXR/CAR-mediated pathway and induce CYP3A. Biochem Pharmacol 79:270–276
   PubMed Web of Science ®Google Scholar
• Chintharlapalli S, Papineni S, Jutooru I, et al. (2007). Structure-dependent activity of glycyrrhetinic acid derivatives as peroxisome proliferator-activated receptor {gamma} agonists in colon cancer cells. Mol Cancer Ther 6:1588–1598
   PubMed Web of Science ®Google Scholar
• Chladek J, Grim J, Martinkova J, et al. (2005). Low-dose methotrexate pharmacokinetics and pharmacodynamics in the therapy of severe psoriasis. Basic Clin Pharmacol Toxicol 96:247–248
   PubMed Web of Science ®Google Scholar
• Choi JS, Han JY, Ahn HK, et al. (2013). Fetal and neonatal outcomes in women reporting ingestion of licorice (Glycyrrhiza uralensis) during pregnancy. Planta Med 79:97–101
   PubMed Web of Science ®Google Scholar
• Eisenbrand G. (2006). Glycyrrhizin. Mol Nutr Food Res 50:1087–1088
   PubMed Web of Science ®Google Scholar
• Fenwick GR. (1990). Liquorice, Glycyrrhiza glabra L. – Composition, uses and analysis. Food Chem 38:119–143
   Web of Science ®Google Scholar
• Fiore C, Eisenhut M, Ragazzi E, et al. (2005). A history of the therapeutic use of liquorice in Europe. J Ethnopharmacol 99:317–324
   PubMed Web of Science ®Google Scholar
• Foti RS, Rock DA, Wienkers LC, et al. (2010). Selection of alternative CYP3A4 probe substrates for clinical drug interaction studies using in vitro data and in vivo simulation. Drug Metab Dispos 38:981–987
   PubMed Web of Science ®Google Scholar
• Fu D. (2013). Where is it and how does it get there – Intracellular localization and traffic of P-glycoprotein. Front Oncol 3:321
   PubMedGoogle Scholar
• Fu Y, Zhou E, Wei Z, et al. (2014). Glycyrrhizin inhibits lipopolysaccharide-induced inflammatory response by reducing TLR4 recruitment into lipid rafts in RAW264.7 cells. Biochim Biophys Acta 1840:1755–1764
   PubMed Web of Science ®Google Scholar
• Fujita K. (2004). Food-drug interactions via human cytochrome P450 3A (CYP3A). Drug Metab Drug Interact 20:195–217
   PubMedGoogle Scholar
• Halama B, Hohmann N, Burhenne J, et al. (2013). A nanogram dose of the CYP3A probe substrate midazolam to evaluate drug interactions. Clin Pharmacol Ther 93:564–571
   PubMed Web of Science ®Google Scholar
• Han HK. (2011). Role of transporters in drug interactions. Arch Pharm Res 34:1865–1877
   PubMed Web of Science ®Google Scholar
• Hasler F, Krapf R, Brenneisen R, et al. (1993). Determination of 18 beta-glycyrrhetinic acid in biological fluids from humans and rats by solid-phase extraction and high-performance liquid chromatography. J Chromatogr 620:73–82
   PubMed Web of Science ®Google Scholar
• Hattori M, Sakamoto T, Kobashi K, et al. (1983). Metabolism of glycyrrhizin by human intestinal flora. Planta Med 48:38–42
   PubMed Web of Science ®Google Scholar
• Hattori M, Sakamoto T, Yamagishi T, et al. (1985). Metabolism of glycyrrhizin by human intestinal flora. II. Isolation and characterization of human intestinal bacteria capable of metabolizing glycyrrhizin and related compounds. Chem Pharm Bull (Tokyo) 33:210–217
   PubMed Web of Science ®Google Scholar
• Horikawa M, Kato Y, Tyson CA, et al. (2002). The potential for an interaction between MRP2 (ABCC2) and various therapeutic agents: Probenecid as a candidate inhibitor of the biliary excretion of irinotecan metabolites. Drug Metab Pharmacokinet 17:23–33
   PubMedGoogle Scholar
• Hou YC, Lin SP, Chao PD. (2012). Liquorice reduced cyclosporine bioavailability by activating P-glycoprotein and CYP 3A. Food Chem 135:2307–2312
   PubMed Web of Science ®Google Scholar
• Huang L, Huang M, Li YH, et al. (2013a). Up-regulatation of CYP3A expression through pregnent X receptor by praeruptorin D isolated from Peucedanum praeruptorum Dunn. J Ethnopharmacol 148:596–602
   PubMed Web of Science ®Google Scholar
• Huang YP, Cao YF, Fang ZZ, et al. (2013b). Glycyrrhetinic acid exhibits strong inhibitory effects towards UDP-glucuronosyltransferase (UGT) 1A3 and 2B7. Phytother Res 27:1358–1361
   PubMed Web of Science ®Google Scholar
• Ichikawa T, Ishida S, Sakiya Y, et al. (1986). Biliary excretion and enterohepatic cycling of glycyrrhizin in rats. J Pharm Sci 75:672–675
   PubMed Web of Science ®Google Scholar
• Ince I, Knibbe CA, Danhof M, et al. (2013). Developmental changes in the expression and function of cytochrome P450 3A isoforms: Evidence from in vitro and in vivo investigations. Clin Pharmacokinet 52:333–345
   PubMed Web of Science ®Google Scholar
• Isbrucker RA, Burdock GA. (2006). Risk and safety assessment on the consumption of Licorice root (Glycyrrhiza sp.), its extract and powder as a food ingredient, with emphasis on the pharmacology and toxicology of glycyrrhizin. Regul Toxicol Pharmacol 46:167–192
   PubMed Web of Science ®Google Scholar
• Ishida S, Sakiya Y, Ichikawa T, et al. (1993). Uptake of glycyrrhizin by isolated rat hepatocytes. Biol Pharm Bull 16:293–7
   PubMed Web of Science ®Google Scholar
• Ismair M. (2003). Interactions of glycyrrhizin with organic anion transporting polypeptides of rat and human liver. Hepatol Res 26:343–347
   PubMed Web of Science ®Google Scholar
• James MO, Ambadapadi S. (2013). Interactions of cytosolic sulfotransferases with xenobiotics. Drug Metab Rev 45:401–414
   PubMed Web of Science ®Google Scholar
• Jayasooriya RG, Dilshara MG, Park SR, et al. (2014). 18beta-Glycyrrhetinic acid suppresses TNF-alpha induced matrix metalloproteinase-9 and vascular endothelial growth factor by suppressing the Akt-dependent NF-kappaB pathway. Toxicol In Vitro 28:751–758
   PubMed Web of Science ®Google Scholar
• Jeong HG, You HJ, Park SJ, et al. (2002). Hepatoprotective effects of 18β-glycyrrhetinic acid on carbon tetrachloride-induced liver injury: Inhibition of cytochrome P450 2e1 expression. Pharmacol Res 46:221–227
   PubMed Web of Science ®Google Scholar
• Jing J, Ren W, Chen X, et al. (2008). Glucuronide-sulfate diconjugate as a novel metabolite of glycyrrhetic acid in rat bile. Drug Metab Pharmacokinet 23:175–180
   PubMed Web of Science ®Google Scholar
• Kai G, Yu W, Jing Y, et al. (2007). CYP3A1/2 and 2C9/10 in rat liver microsomes mediate 22 <alpha>-and 24-hydroxylation of 18<alpha >-GA. Chin J Clin Pharmacol Ther 12:1255–1306
   Google Scholar
• Katoh M, Yoshioka Y, Nakagawa N, et al. (2009). Effects of Japanese herbal medicine, Kampo, on human UGT1A1 activity. Drug Metab Pharmacokinet 24:226–234
   PubMed Web of Science ®Google Scholar
• Kiang TK, Ensom MH, Chang TK. (2005). UDP-glucuronosyltransferases and clinical drug–drug interactions. Pharmacol Ther 106:97–132
   PubMed Web of Science ®Google Scholar
• Kim DH, Hong SW, Kim BT, et al. (2000). Biotransformation of glycyrrhizin by human intestinal bacteria and its relation to biological activities. Arch Pharm Res 23:172–177
   PubMed Web of Science ®Google Scholar
• Kočevar Glavač N, Kreft S. (2012). Excretion profile of glycyrrhizin metabolite in human urine. Food Chem 131:305–308
   Web of Science ®Google Scholar
• Koga K, Ohmachi K, Kawashima S, et al. (2000). Determination of 18alpha-glycyrrhizin and 18beta-glycyrrhizin in dog plasma by high-performance liquid chromatography. J Chromatogr B Biomed Sci Appl 738:165–168
   PubMedGoogle Scholar
• Konig J, Muller F, Fromm MF. (2013). Transporters and drug–drug interactions: Important determinants of drug disposition and effects. Pharmacol Rev 65:944–966
   PubMed Web of Science ®Google Scholar
• Kronbach T, Fischer V, Meyer UA. (1988). Cyclosporine metabolism in human liver: Identification of a cytochrome P-450III gene family as the major cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs. Clin Pharmacol Ther 43:630–635
   PubMed Web of Science ®Google Scholar
• Lee CS, Yang JC, Kim YJ, et al. (2010). 18beta-Glycyrrhetinic acid potentiates apoptotic effect of trichostatin A on human epithelial ovarian carcinoma cell lines. Eur J Pharmacol 649:354–361
   PubMed Web of Science ®Google Scholar
• Lee KW, Ho WS. (2013). 18beta-glycyrrhetinic acid induces UDP-glucuronosyltransferase in rats. Protein Pept Lett 20:1360–1364
   PubMed Web of Science ®Google Scholar
• Lee Y, Jeong S, Kim W, et al. (2013). Glycyrrhizin enhances therapeutic activity of a colon-specific methylprednisolone prodrug against experimental colitis. Dig Dis Sci 58:1226–1234
   PubMed Web of Science ®Google Scholar
• Leucuta SE, Vlase L. (2006). Pharmacokinetics and metabolic drug interactions. Curr Clin Pharmacol 1:5–20
   PubMedGoogle Scholar
• Li AP, Kaminski DL, Rasmussen A. (1995). Substrates of human hepatic cytochrome P450 3A4. Toxicology 104:1–8
   PubMed Web of Science ®Google Scholar
• Li JY, Cao HY, Liu P, et al. (2014a). Glycyrrhizic acid in the treatment of liver diseases: Literature review. Biomed Res Int 2014:1–15
   Web of Science ®Google Scholar
• Li L, Hu H, Xu S, et al. (2012). Roles of UDP-glucuronosyltransferases in phytochemical metabolism of herbal medicines and the associated herb-drug interactions. Curr Drug Metab 13:615–623
   PubMed Web of Science ®Google Scholar
• Li R, Barton HA,Varma MV. (2014b). Prediction of pharmacokinetics and drug–drug interactions when hepatic transporters are involved. Clin Pharmacokinet 53:659–678
   PubMed Web of Science ®Google Scholar
• Li X, Hu J, Wang B, et al. (2014c). Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: Herb-drug interactions mediated via P-gp. Toxicol Appl Pharmacol 275:163–175
   PubMed Web of Science ®Google Scholar
• Li Y, Wang Q, Yao X, et al. (2010). Induction of CYP3A4 and MDR1 gene expression by baicalin, baicalein, chlorogenic acid, and ginsenoside Rf through constitutive androstane receptor- and pregnane X receptor-mediated pathways. Eur J Pharmacol 640:46–54
   PubMed Web of Science ®Google Scholar
• Lin SP, Tsai SY, Hou YC, et al. (2009). Glycyrrhizin and licorice significantly affect the pharmacokinetics of methotrexate in rats. J Agric Food Chem 57:1854–1859
   PubMed Web of Science ®Google Scholar
• Liu Y, Zhang JW, Li W, et al. (2006). Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes. Toxicol Sci 91:356–364
   PubMed Web of Science ®Google Scholar
• Lu Y, Zhu J, Chen X, et al. (2009). Identification of human UDP-glucuronosyltransferase isoforms responsible for the glucuronidation of glycyrrhetinic acid. Drug Metab Pharmacokinet 24:523–528
   PubMed Web of Science ®Google Scholar
• Ma C, Ma Z, Liao XL, et al. (2013). Immunoregulatory effects of glycyrrhizic acid exerts anti-asthmatic effects via modulation of Th1/Th2 cytokines and enhancement of CD4+CD25+Foxp3+ regulatory T cells in ovalbumin-sensitized mice. J Ethnopharmacol 148:755–762
   PubMed Web of Science ®Google Scholar
• Makino T, Ohtake N, Watanabe A, et al. (2008). Down-regulation of a hepatic transporter multidrug resistance-associated protein 2 is involved in alteration of pharmacokinetics of glycyrrhizin and its metabolites in a rat model of chronic liver injury. Drug Metab Dispos 36:1438–1443
   PubMed Web of Science ®Google Scholar
• Makino T, Okajima K, Uebayashi R, et al. (2012). 3-Monoglucuronyl-glycyrrhretinic acid is a substrate of organic anion transporters expressed in tubular epithelial cells and plays important roles in licorice-induced pseudoaldosteronism by inhibiting 11beta-hydroxysteroid dehydrogenase 2. J Pharmacol Exp Ther 342:297–304
   PubMed Web of Science ®Google Scholar
• Matsui S, Matsumoto H, Sonoda Y, et al. (2004). Glycyrrhizin and related compounds down-regulate production of inflammatory chemokines IL-8 and eotaxin 1 in a human lung fibroblast cell line. Int Immunopharmacol 4:1633–1644
   PubMed Web of Science ®Google Scholar
• Matsunami H, Lynch SV, Balderson GA, et al. (1993). Use of glycyrrhizin for recurrence of hepatitis B after liver transplantation. Am J Gastroenterol 88:152–153
   PubMed Web of Science ®Google Scholar
• Moon A, Lee MK, Kim SH, et al. (1995). Effect of Glycyrrhizae radix on the glucuronidation in rat liver. Arch Pharm Res 18:320–324
   Web of Science ®Google Scholar
• Nabekura T, Yamaki T, Ueno K, et al. (2008). Inhibition of P-glycoprotein and multidrug resistance protein 1 by dietary phytochemicals. Cancer Chemother Pharmacol 62:867–873
   PubMed Web of Science ®Google Scholar
• Nagai T, Egashira T, Kudo Y, et al. (1992). Attenuation of dysfunction in the ischemia-reperfused liver by glycyrrhizin. Jpn J Pharmacol 58:209–218
   PubMedGoogle Scholar
• Nakagawa N, Katoh M, Yoshioka Y, et al. (2009). Inhibitory effects of Kampo medicine on human UGT2B7 activity. Drug Metab Pharmacokinet 24:490–499
   PubMed Web of Science ®Google Scholar
• Olukoga A, Donaldson D. (1998). Historical perspectives on health. The history of liquorice: The plant, its extract, cultivation, commercialisation and etymology. J R Soc Promot Health 118:300–304
   PubMedGoogle Scholar
• Paolini M, Barillari J, Broccoli M, et al. (1999). Effect of liquorice and glycyrrhizin on rat liver carcinogen metabolizing enzymes. Cancer Lett 145:35–42
   PubMed Web of Science ®Google Scholar
• Paolini M, Pozzetti L, Sapone A, et al. (1998). Effect of licorice and glycyrrhizin on murine liver CYP-dependent monooxygenases. Life Sci 62:571–582
   PubMed Web of Science ®Google Scholar
• Parke DV, Pollock S, Williams RT. (1963). The fate of tritium-labelled beta-glycyrrhetic acid in the rat. J Pharm Pharmacol 15:500–6
   PubMed Web of Science ®Google Scholar
• Podolsky DK. (1991). Inflammatory bowel disease (2). N Engl J Med 325:1008–1016
   PubMed Web of Science ®Google Scholar
• Raub TJ. (2006). P-glycoprotein recognition of substrates and circumvention through rational drug design. Mol Pharm 3:3–25
   PubMed Web of Science ®Google Scholar
• Rossi T, Fano RA, Castelli M, et al. (1999). Correlation between high intake of glycyrrhizin and myolysis of the papillary muscles: An experimental in vivo study. Pharmacol Toxicol 85:221–229
   PubMedGoogle Scholar
• Rowland A, Miners JO, Mackenzie PI. (2013). The UDP-glucuronosyltransferases: Their role in drug metabolism and detoxification. Int J Biochem Cell Biol 45:1121–1132
   PubMed Web of Science ®Google Scholar
• Sabbioni C, Mandrioli R, Ferranti A, et al. (2005). Separation and analysis of glycyrrhizin, 18β-glycyrrhetic acid and 18α-glycyrrhetic acid in liquorice roots by means of capillary zone electrophoresis. J Chromatogr A 1081:65–71
   PubMed Web of Science ®Google Scholar
• Sabouri Ghannad M, Mohammadi A, Safiallahy S, et al. (2014). The effect of aqueous extract of Glycyrrhiza glabra on herpes simplex virus 1. Jundishapur J Microbiol 7:e11616
   Google Scholar
• Sasaki K, Yonebayashi S, Yoshida M, et al. (2003). Improvement in the bioavailability of poorly absorbed glycyrrhizin via various non-vascular administration routes in rats. Int J Pharm 265:95–102
   PubMed Web of Science ®Google Scholar
• Seki H, Ohyama K, Sawai S, et al. (2008). Licorice beta-amyrin 11-oxidase, a cytochrome P450 with a key role in the biosynthesis of the triterpene sweetener glycyrrhizin. Proc Natl Acad Sci USA 105:14204–14209
   PubMed Web of Science ®Google Scholar
• Shen G, Zhuang X, Xiao W, et al. (2014). Role of CYP3A in regulating hepatic clearance and hepatotoxicity of triptolide in rat liver microsomes and sandwich-cultured hepatocytes. Food Chem Toxicol 71:90–96
   PubMed Web of Science ®Google Scholar
• Shu Y, Wang LS, Xiao WM, et al. (2000). Probing CYP2C19 and CYP3A4 activities in Chinese liver microsomes by quantification of 5-hydroxyomeprazole and omeprazole sulphone. Acta Pharmacol Sin 21:753–758
   PubMed Web of Science ®Google Scholar
• Silva R, Vilas-Boas V, Carmo H, et al. (2014). Modulation of P glycoprotein efflux pump: Induction and activation as a therapeutic strategy. Pharmacol Ther. [Epub ahead of print]. doi: 10.1016/j.pharmthera.2014.11.013
   Google Scholar
• Siracusa L, Saija A, Cristani M, et al. (2011). Phytocomplexes from liquorice (Glycyrrhiza glabra L.) leaves – Chemical characterization and evaluation of their antioxidant, anti-genotoxic and anti-inflammatory activity. Fitoterapia 82:546–556
   PubMed Web of Science ®Google Scholar
• Spriet I, Meersseman W, de Hoon J, et al. (2009). Mini-series: II. Clinical aspects. Clinically relevant CYP450-mediated drug interactions in the ICU. Intensive Care Med 35:603–612
   PubMed Web of Science ®Google Scholar
• Tachibana T, Kato M, Takano J, et al. (2010). Predicting drug–drug interactions involving the inhibition of intestinal CYP3A4 and P-glycoprotein. Curr Drug Metab 11:762–777
   PubMed Web of Science ®Google Scholar
• Tai T, Huang X, Su Y, et al. (2014). Glycyrrhizin accelerates the metabolism of triptolide through induction of CYP3A in rats. J Ethnopharmacol 152:358–363
   PubMed Web of Science ®Google Scholar
• Takeda S, Ishthara K, Wakui Y, et al. (1996). Bioavailability study of glycyrrhetic acid after oral administration of glycyrrhizin in rats; relevance to the intestinal bacterial hydrolysis. J Pharm Pharmacol 48:902–905
   PubMed Web of Science ®Google Scholar
• Thyss A, Milano G, Kubar J, et al. (1986). Clinical and pharmacokinetic evidence of a life-threatening interaction between methotrexate and ketoprofen. Lancet 1:256–258
   PubMed Web of Science ®Google Scholar
• Tu JH, He YJ, Chen Y, et al. (2010a). Effect of glycyrrhizin on the activity of CYP3A enzyme in humans. Eur J Clin Pharmacol 66:805–810
   PubMed Web of Science ®Google Scholar
• Tu JH, Hu DL, Dai LL, et al. (2010b). Effect of glycyrrhizin on CYP2C19 and CYP3A4 activity in healthy volunteers with different CYP2C19 genotypes. Xenobiotica 40:393–399
   PubMed Web of Science ®Google Scholar
• Tukey RH, Strassburg CP. (2000). Human UDP-glucuronosyltransferases: Metabolism, expression, and disease. Annu Rev Pharmacol Toxicol 40:581–616
   PubMed Web of Science ®Google Scholar
• Vaalburg W, Hendrikse NH, Elsinga PH, et al. (2005). P-glycoprotein activity and biological response. Toxicol Appl Pharmacol 207:257–260
   PubMedGoogle Scholar
• Vampa G, Benvenuti S, Rossi T. (1992). Determination of glycyrrhizin and 18 alpha-, 18 beta-glycyrrhetinic acid in rat plasma by high-performance thin-layer chromatography. Farmaco 47:825–832
   PubMedGoogle Scholar
• van Rossum TG, Vulto AG, de Man RA, et al. (1998). Glycyrrhizin as a potential treatment for chronic hepatitis C. Aliment Pharmacol Ther 12:199–205
   PubMed Web of Science ®Google Scholar
• van Uum SH. (2005). Liquorice and hypertension. Neth J Med 63:119–120
   PubMed Web of Science ®Google Scholar
• Wang D, Wong HK, Feng YB, et al. (2014a). 18beta-glycyrrhetinic acid induces apoptosis in pituitary adenoma cells via ROS/MAPKs-mediated pathway. J Neurooncol 116:221–230
   PubMed Web of Science ®Google Scholar
• Wang Q, Shi L, Tang X, et al. (2014b). Pharmacokinetic study of multiple active constituents from Kushen-Gancao Decoction after oral administration in rat by HPLC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 965:19–26
   PubMed Web of Science ®Google Scholar
• Wang X, Zhang H, Chen L, et al. (2013). Liquorice, a unique “guide drug” of traditional Chinese medicine: A review of its role in drug interactions. J Ethnopharmacol 150:781–790
   PubMed Web of Science ®Google Scholar
• Wang YC, Yang YS. (2007). Simultaneous quantification of flavonoids and triterpenoids in licorice using HPLC. J Chromatogr B Analyt Technol Biomed Life Sci 850:392–399
   PubMed Web of Science ®Google Scholar
• Wang YG, Zhou JM, Ma ZC, et al. (2012). Pregnane X receptor mediated-transcription regulation of CYP3A by glycyrrhizin: A possible mechanism for its hepatoprotective property against lithocholic acid-induced injury. Chem Biol Interact 200:11–20
   PubMed Web of Science ®Google Scholar
• Xu R, Zhang X, Yang J, et al. (2012). Effects of glycyrrhizin on biliary transport and hepatic levels of glutathione in rats. Biopharm Drug Dispos 33:235–245
   PubMed Web of Science ®Google Scholar
• Yan M, Fang PF, Li HD, et al. (2013). Lack of effect of continuous glycyrrhizin administration on the pharmacokinetics of the P-glycoprotein substrate talinolol in healthy volunteers. Eur J Clin Pharmacol 69:515–521
   PubMed Web of Science ®Google Scholar
• Yan M, Li L, Li H, et al. (2012). Effect of 18alpha-glycyrrhizic acid and 18beta-glycyrrhizic acid on P-gp function and expression in Caco-2 cells. Zhongguo Zhong Yao Za Zhi 37:99–103
   PubMedGoogle Scholar
• Yoshida N, Koizumi M, Adachi I, et al. (2006). Inhibition of P-glycoprotein-mediated transport by terpenoids contained in herbal medicines and natural products. Food Chem Toxicol 44:2033–2039
   PubMed Web of Science ®Google Scholar
• Yoshida N, Takada T, Yamamura Y, et al. (2008). Inhibitory effects of terpenoids on multidrug resistance-associated protein 2- and breast cancer resistance protein-mediated transport. Drug Metab Dispos 36:1206–1211
   PubMed Web of Science ®Google Scholar
• Yu C, Ye S, Sun H, et al. (2009). PXR-mediated transcriptional activation of CYP3A4 by cryptotanshinone and tanshinone IIA. Chem Biol Interact 177:58–64
   PubMed Web of Science ®Google Scholar
• Yu K, Chen F, Li C. (2012). Absorption, disposition, and pharmacokinetics of saponins from Chinese medicinal herbs: What do we know and what do we need to know more? Curr Drug Metab 13:577–598
   PubMed Web of Science ®Google Scholar
• Zani F, Cuzzoni MT, Daglia M, et al. (1993). Inhibition of mutagenicity in Salmonella typhimurium by Glycyrrhiza glabra extract, glycyrrhizinic acid, 18 alpha- and 18 beta-glycyrrhetinic acids. Planta Med 59:502–507
   PubMed Web of Science ®Google Scholar
• Zhang MF, Shen YQ. (2011). Recent developments on study of hepatoprotective activities of 18α-glycyrrhizic acid. Anti Infect Pharm 8:11–13
   Google Scholar
• Zhang YD, Lorenzo B, Reidenberg MM. (1994). Inhibition of 11 beta-hydroxysteroid dehydrogenase obtained from guinea pig kidney by furosemide, naringenin and some other compounds. J Steroid Biochem Mol Biol 49:81–85
   PubMed Web of Science ®Google Scholar
• Zhao K, Ding M, Cao H, et al. (2012). In-vitro metabolism of glycyrrhetinic acid by human and rat liver microsomes and its interactions with six CYP substrates. J Pharm Pharmacol 64:1445–1451
   PubMed Web of Science ®Google Scholar
• Zhou SF. (2008). Drugs behave as substrates, inhibitors and inducers of human cytochrome P450 3A4. Curr Drug Metab 9:310–322
   PubMed Web of Science ®Google Scholar
• Zou Q, Wei P, Li J, et al. (2009). Simultaneous determination of 18alpha- and 18beta-glycyrrhetic acid in human plasma by LC-ESI-MS and its application to pharmacokinetics. Biomed Chromatogr 23:54–62
   PubMed Web of Science ®Google Scholar