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Cited by 15Mangiferin and Mango ExtractsPharmacogenetics and Drug MetabolismDrug Transport and Resistance Mechanisms

In Vitro Comparative Study of the Inhibitory Effects of Mangiferin and Its Aglycone Norathyriol towards UDP-Glucuronosyl Transferase (UGT) Isoforms

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Sun, Dan, Zhang, Chun-Ze, Ran, Rui-Xue, Cao, Yun-Feng, Du, Zuo, Fu, Zhi-Wei, Huang, Chun-Ting, Zhao, Zhen-Ying +2 more·2017·Molecules
DOI 10.3390/molecules22061008PMC PMC6152678
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Abstract

Mangiferin (MGF), the predominant constituent of extracts of the mango plant Mangifera Indica L., has been investigated extensively because of its remarkable pharmacological effects. In vitro recombinant UGTs-catalyzed glucuronidation of 4-methylumbelliferone (4-MU) was used to investigate the inhibition of mangiferin and aglycone norathyriol towards various isoforms of UGTs in our study, which evaluated the inhibitory capacity of MGF and its aglycone norathyriol (NTR) towards UDP-glucuronosyltransferase (UGT) isoforms. Initial screening experiment showed that deglycosylation of MGF into NTR strongly increased the inhibitory effects towards almost all the tested UGT isoforms at a concentration of 100 μM. Kinetic experiments were performed to further characterize the inhibition of UGT1A3, UGT1A7 and UGT1A9 by NTR. NTR competitively inhibited UGT1A3, UGT1A7 and UGT1A9, with an IC50 value of 8.2, 4.4, and 12.3 μM, and a Ki value of 1.6, 2.0, and 2.8 μM, respectively. In silico docking showed that only NTR could dock into the activity cavity of UGT1A3, UGT1A7 and UGT1A9. The binding free energy of NTR to UGT1A3, 1A7, 1A9 were −7.4, −7.9 and −4.0 kcal/mol, respectively. Based on the inhibition evaluation standard ([I]/Ki < 0.1, low possibility; 0.1 < [I]/Ki < 1, medium possibility; [I]/Ki > 1, high possibility), an in vivo herb–drug interaction between MGF/NTR and drugs mainly undergoing UGT1A3-, UGT1A7- or UGT1A9-catalyzed metabolism might occur when the plasma concentration of NTR is above 1.6, 2.0 and 2.8 μM, respectively.

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  • Evaluation of drug-drug interaction risks for MGF is sparse.

    “ii) sparse evaluation of drug-drug interaction risks given pathway cross-talk (for example, with PI3K/Akt, AMPK or NF-κB modulators) (181-183)”

    From Mangiferin in human disease: Multifaceted mechanisms and applications (Review) (2026) · cites this paper as [182]

    The Introduction (page unavailable) says only a few articles had examined potential herb–drug interactions involving MGF and NTR, supporting the claim that risk evaluation was sparse. The paper studies interactions involving drug-metabolizing enzymes; it does not connect the evaluation gap to pathway cross-talk or interactions with PI3K/Akt, AMPK, or NF-κB modulators. (LLM, conf=0.86)

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  1. [1]Cai F. Xu W. Wei H. Sun L.N. Gao S.H. Yang Q. Feng J. Zhang F. Chen W.S. Simultaneous determination of active xanthone glycosides, timosaponins and alkaloids in rat plasma after oral administration of Zi-Shen Pill extract for the pharmacokinetic study by liquid chromatography-tandem mass spectrometry J. Chromatogr. B 2010 878 1845 1854 10.1016/j.jchromb.2010.05.024 20541984 · DOI
  2. [2]Das S. Nageshwar R.B. Satish R.B.S. Mangiferin attenuates methylmercury induced cytotoxicity against IMR-32, human neuroblastoma cells by the inhibition of oxidative stress and free radical scavenging potential Chem.-Biol. Interact. 2011 193 129 140 10.1016/j.cbi.2011.06.002 21703249 · DOI
  3. [4]Girón M.D. Sevillano N. Salto R. Haidour A. Manzano M. Jiménez M.L. Rueda R. López-Pedrosa J.M. Salacia oblonga extract increases glucose transporter 4-mediated glucose uptake in L6rat myotubes: Role of mangiferin Clin. Nutr. 2009 28 565 574 10.1016/j.clnu.2009.04.018 19477051 · DOI · Paper page
  4. [5]Apontes P. Liu Z.B. Su K. Benard O. Youn D.Y. Li X.S. Li W. Mirza R.H. Bastie C.C. Jelicks L.A. Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets Diabetes 2014 63 3626 3636 10.2337/db14-0006 24848064 PMC4207399 · DOI · Paper page
  5. [6]Shoji K. Tsubaki M. Yamazoe Y. Satou T. Itoh T. Kidera Y. Tanimori Y. Yanae M. Matsuda H. Taga A. Mangiferin induces apoptosis by suppressing Bcl-xL and XIAP expressions and nuclear entry of NF-ĸB in HL-60 cells Arch. Pharm. Res. 2011 34 469 475 10.1007/s12272-011-0316-8 21547680 · DOI · Paper page
  6. [7]Savikin K. Menković N. Zdunić G. Stević T. Radanović D. Janković T. Antimicrobial activity of Gentiana lutea L. extracts Z. Naturforschung C 2009 64 339 342 10.1515/znc-2009-5-606 19678535 · DOI
  7. [8]Wang R.R. Gao Y.D. Ma C.H. Zhang X.J. Huang C.G. Huang J.F. Zheng Y.T. Mangiferin, an anti-HIV-1 agent targeting protease and effective against resistant strains Molecules 2011 16 4264 4277 10.3390/molecules16054264 21610656 PMC6263262 · DOI
  8. [9]Jagetia G.C. Baliga M.S. Radioprotection by mangiferin in DBAxC57BL mice: A preliminary study Phytomedicine 2005 12 209 215 10.1016/j.phymed.2003.08.003 15830843 · DOI
  9. [10]El-Seedi H.R. El-Barbary M.A. El-Ghorab D.M.H. Bohlin L. Borg-Karlson A.K. Goransson U. Verpoorte R. Recent insights into the biosynthesis and biological activities of natural xanthones Curr. Med. Chem. 2010 17 854 901 10.2174/092986710790712147 20156171 · DOI
  10. [11]El-Seedi H.R. El-Ghorab D.M. El-Barbary M.A. Zayed M.F. Goransson U. Larsson S. Verpoorte R. Naturally occurring xanthones; latest investigations: isolation, structure elucidation and chemosystematic significance Curr. Med. Chem. 2009 16 2581 2626 10.2174/092986709788682056 19601799 · DOI
  11. [12]Liu Y.M. Xu F.P. Zeng X. Yang L. Deng Y.H. Wu Z.F. Feng Y. Li X. Application of a liquid chromatography/tandem mass spectrometry method to pharmacokinetic study of mangiferin in rats J. Chromatogr. B 2010 878 3345 3350 10.1016/j.jchromb.2010.10.014 21081292 · DOI
  12. [13]Han D.D. Chen C.J. Cong Z. Zhang Y. Tang X. Determination of mangiferin in rat plasma by liquid–liquid extraction with UPLC–MS/MS J. Pharm. Biomed. Anal. 2010 51 260 263 10.1016/j.jpba.2009.07.021 19699046 · DOI · Paper page
  13. [14]Rowland M. Influence of route of administration on drug availability J. Pharm. Sci. 1972 61 70 74 10.1002/jps.2600610111 5019220 · DOI
  14. [15]Pond S.M. Tozer T.N. First-pass elimination basic concepts and clinical consequences Clin. Pharmacokinet. 1984 9 1 25 10.2165/00003088-198409010-00001 6362950 · DOI
  15. [17]Ma C.H. Wang L.X. Tang Y.H. Fan M.B. Xiao H.B. Huang C.G. Identification of major xanthones and steroidal saponins in rat urine by liquid chromatography–atmospheric pressure chemical ionization mass spectrometry technology following oral administration of Rhizoma Anemarrhenae decoction Biomed. Chromatogr. 2008 22 1066 1083 10.1002/bmc.1026 18506725 · DOI
  16. [18]Sanugul K. Akao T. Li Y. Kakiuchi N. Nakamura N. Hattori M. Isolation of a human intestinal bacterium that transforms mangiferin to norathyriol and inducibility of the enzyme that cleaves a C-glucosyl bond Biol. Pharm. Bull. 2005 28 1672 1678 10.1248/bpb.28.1672 16141538 · DOI
  17. [19]Braune A. Blaut M. Deglycosylation of puerarin and other aromatic C-glucosides by a newly isolated human intestinal bacterium Environ. Microbiol. 2011 13 482 494 10.1111/j.1462-2920.2010.02352.x 20946528 · DOI
  18. [20]Chieli E. Romiti N. Rodeiro I. Garrido G. In vitro effects of Mangiferaindica and polyphenols derived on ABCB1/P-glycoprotein activity Food Chem. Toxicol. 2009 47 2703 2710 10.1016/j.fct.2009.07.017 19632288 · DOI · Paper page
  19. [21]Hsu M.F. Lin C.N. Lu M.C. Wang J.P. Inhibition of the arachidonic acid cascade by norathyriol via blockade of cyclooxygenase and lipoxygenase activity in neutrophils Naunyn-Schmiedeberg’s Arch. Pharmacol. 2004 369 507 515 10.1007/s00210-004-0922-9 15083266 · DOI
  20. [22]Lee H.Z. Lin W.C. Yeh F.T. Lin C.N. Wu C.H. Decreased protein kinase C activation mediates inhibitory effect of norathyriol on serotonin-mediated endothelial permeability Eur. J. Pharmacol. 1998 353 303 313 10.1016/S0014-2999(98)00385-9 9726661 · DOI
  21. [23]Li J.X. Malakhova M. Mottamal M. Reddy K. Kurinov I. Carper A. Langfald A. Oi N. Kim O.M. Zhu F. Norathyriol suppresses skin cancers induced by solar ultraviolet radiation by targeting ERK kinases Cancer Res. 2012 72 260 270 10.1158/0008-5472.CAN-11-2596 22084399 PMC3251698 · DOI
  22. [24]Wang F. Yan J.M. Niu Y.F. Li Y. Lin H. Liu X. Liu J.K. Li L. Mangiferin and its aglycone, norathyriol, improve glucose metabolism by activation of AMP activated protein kinase Pharm. Biol. 2014 52 68 73 10.3109/13880209.2013.814691 24033319 · DOI
  23. [26]Oda S. Fukami T. Yokoi T. Nakajima M. A comprehensive review of UDP-glucuronosyltransferase and esterases for drug development Drug Metab. Pharmacokinet. 2015 30 30 51 10.1016/j.dmpk.2014.12.001 25760529 · DOI
  24. [27]Kiang T.K. Ensom M.H. Chang T.K. UDP-glucuronosyltransferases and clinical drug-drug interactions Pharm. Ther. 2005 106 97 132 10.1016/j.pharmthera.2004.10.013 15781124 · DOI
  25. [28]Tukey R.H. Strassburg C.P. Human UDP-Glucuronosyltransferases: Metabolism, Expression, and Disease Annu. Rev. Pharmacol. Toxicol. 2000 40 581 616 10.1146/annurev.pharmtox.40.1.581 10836148 · DOI
  26. [29]Rowland A. Miners J. Mackenzie P.I. The UDP-glucuronosyltransferases: Their role in drug metabolism and detoxification Int. J. Biochem. Cell Biol. 2013 45 1121 1132 10.1016/j.biocel.2013.02.019 23500526 · DOI
  27. [30]Wang X. Structure, mechanism and engineering of plant natural product glycosyltransferases FEBS Lett. 2009 583 3303 3309 10.1016/j.febslet.2009.09.042 19796637 · DOI
  28. [31]Judith M.J. Quincy C.S.C. Prabhu R. Soma D. Ruslan S. Michael B.S. UGT1A1 polymorphism and hyperbilirubinemia in a patient who received sorafenib Cancer Chemother. Pharmacol. 2009 65 1 4 19672597
  29. [32]Bourcier K. Hyland R. Kempshall S. Jones R. Mximilien J. Irvine N. Jones B. Investigation into UDP-Glucuronosyltransferase (UGT) enzyme kinetics of imidazole- and triazole-containing antifungal drugs in human Liver microsomes and recombinant UGT enzymes Drug. Metab. Dispos. 2010 38 923 929 10.1124/dmd.109.030676 20304965 · DOI
  30. [33]Ran R.X. Zhang C.Z. Li R.S. Chen B.W. Zhang W.H. Zhao Z.Y. Fu Z.W. Du Z. Du X.L. Yang X.L. Evaluation and Comparison of the Inhibition Effect of Astragaloside IV and Aglycone Cycloastragenol on Various UDP-Glucuronosyltransferase (UGT) Isoforms Molecules 2016 21 1616 10.3390/molecules21121616 27916843 PMC6274106 · DOI
  31. [34]Xie H. Wu J. Liu D. Liu M. Zhang H. Huang S. Xiong Y. Xia C. In vitro inhibition of UGT1A3, UGT1A4 by ursolic and oleanolic acid and drug–drug interaction risk prediction Xenobiotica 2016 1 28 10.1080/00498254.2016.1234087 27600106 · DOI
  32. [35]Kim D. Zheng Y.F. Min J.S. Park J.B. Bae S.H. Yoon K.D. Chin Y.W. Oh E. Bae S.K. In vitro, Stereoselective Inhibition of Ginsenosides toward UDP-glucuronosyltransferase (UGT) Isoforms Toxicol. Lett. 2016 259 1 10 10.1016/j.toxlet.2016.07.108 27462006 · DOI
  33. [37]Guo B. Fan X.R. Fang Z.Z. Cao Y.F. Hu C.M. Yang I. Zhang Y.Y. He R.R. Zhu X. Yu Z.W. Deglycosylation of liquiritin strongly enhances its inhibitory potential towards UDP-glucuronosyltransferase (UGT) isoforms Phytother. Res. 2013 27 1232 1236 10.1002/ptr.4855 23065713 · DOI
  34. [38]Cao Y.F. He R.R. Cao J. Chen J.X. Huang T. Liu Y. Drug–Drug Interactions Potential of Icariin and Its Intestinal Metabolites via Inhibition of Intestinal UDP-Glucuronosyltransferases Evid.-Based Complement. Altern. Med. 2012 2 1 8 10.1155/2012/395912 23118789 PMC3479967 · DOI
  35. [39]Zhang H. Zhao Z.Y. Wang T. Wang Y.J. Cui X. Zhang H.J. Fang Z.Z. Inhibition of UDP-Glucuronosyl transferase (UGT) Isoforms by Arctiin and Arctigenin Phytother. Res. 2016 30 1189 1196 10.1002/ptr.5627 27145339 · DOI
  36. [40]Ma G.Y. Cao Y.F. Hu C.M. Fang Z.Z. Sun X.Y. Hong M. Zhu Z.T. Comparison of inhibition capability of scutellarin and scutellarin towards important liver UDP-glucuronosyltransferase (UGT) isoforms Photother. Res. 2014 28 382 386 10.1002/ptr.4990 23620377 · DOI
  37. [41]Wells P.G. Mackenzie P.I. Chowdhury J.R. Glucuronidation and the UDP-glucuronosyltransferases in health and disease Drug Metab. Dispos. Biol. Fate Chem. 2004 32 281 290 10.1124/dmd.32.3.281 14977861 · DOI · Paper page
  38. [42]Trottier J. Verreault M. Grepper S. Monte D. Belanger J. Kaeding J. Inaba T.T. Barbier O. Human UDP-glucuronosyltransferase (UGT)1A3 enzyme conjugates chenodeoxycholic acid in the liver Hepatology 2006 44 1158 1170 10.1002/hep.21362 17058234 · DOI
  39. [43]Mojarrabi B. Butler R. Mackenzie P.I. cDNA cloning and characterization of the human UDP glucuronosyltransferase, UGT1A3 Biochem. Biophys. Res. Commun. 1996 225 785 790 10.1006/bbrc.1996.1251 8780690 · DOI
  40. [44]Green M.D. King C.D. Mojarrabi B. Mackenzie P.I. Teply T.R. Glucuronidation of amines and other xenobiotics catalyzed by expressed human UDP glucuronosyl transferase 1A3 Drug Metab. Dispos. 1998 26 507 512 9616184
  41. [45]Kuehl G.E. Lampe J.W. Potter J.D. Bigler J. Glucuronidation of nonsteroidal anti-inflammatory drugs: Identifying the enzymes responsible in human liver microsomes Drug Metab. Dispos. 2005 33 1027 1035 10.1124/dmd.104.002527 15843492 · DOI
  42. [46]Prueksaritanont T. Zhao J.J. Ma B. Roadcap B.A. Tang C. Qiu Y. Liu L. Pearson P.G. Baillie T.A. Mechanistic studies on metabolic interactions between gemfibrozil and statins J. Pharmacol. Exp. Ther. 2002 301 1042 1051 10.1124/jpet.301.3.1042 12023536 · DOI
  43. [47]Strassburg C.P. Oldhafer K. Manns M.P. Tukey R.H. Differential expression of the UGT1A locus in human liver, biliary, and gastric tissue: Identification of UGT1A7 and UGT1A10 transcripts in extrahepatic tissues Mol. Pharmacol. 1997 52 212 220 9271343
  44. [48]Ritter J.K. Roles of glucuronidation and UDP-glucuronosyltransferases in xenobiotic bioactivation reactions Chem. Biol. Interact. 2000 129 171 193 10.1016/S0009-2797(00)00198-8 11154740 · DOI
  45. [49]Yang S.Y. Qiu Z.X. Zhang Q.Y. Chen J.Y. Chen X.J. Inhibitory Effects of Calf Thymus DNA on Metabolism Activity of CYP450 Enzyme in Human Liver Microsomes Drug Metab. Pharmacokinet. 2014 29 475 481 10.2133/dmpk.DMPK-13-RG-131 25030415 · DOI
  46. [50]Wang H. Ye G. Tang Y.H. Zhu H.Y. Ma R.R. Sun Z.L. Huang C.G. High-performance liquid chromatographic method for the determination of mangiferin in rat plasma and urine Biomed. Chromatogr. 2006 20 1304 1308 10.1002/bmc.695 17006966 · DOI
  47. [51]Hou S. Wang F. Li Y. Li Y. Wang M. Sun D. Sun C. Pharmacokinetic study of mangiferin in human plasma after oral administration Food Chem. 2012 132 289 294 10.1016/j.foodchem.2011.10.079 26434292 · DOI · Paper page
  48. [52]Tian X.T. Gao Y. Xu Z. Lian S. Ma Y.J. Guo X.Z. Hu P. Li Z.X. Huang C.G. Pharmacokinetics of mangiferin and its metabolite—Norathyriol, Part 1: Systemic evaluation of hepatic first-pass effect in vitro, and in vivo Biofactors 2016 42 1 12 10.1002/biof.1291 27130074 · DOI · Paper page
  49. [53]Zhang Q. Cao Y.F. Ran R.X. Li R.S. Wu X. Dong P.P. Zhang Y.Y. Hu C.M. Wang W.M. Strong specific inhibition of UDP-glucuronosyltransferase 2B7 by atractylenolide I and III Phytother. Res. 2016 30 25 30 10.1002/ptr.5496 26536846 · DOI
  50. [54]Fang Z.Z. Wang H.N. Cao Y.F. Sun D.X. Wang L.X. Hong M. Huang T. Chen J.X. Zeng A.J. Enantioselective Inhibition of Carprofen Towards UDPglucuronosyltransferase (UGT) 2B7 Chirality 2015 27 189 193 10.1002/chir.22412 25502512 · DOI
  51. [55]Fang Z.Z. Cao Y.F. Hu C.M. Hong M. Sun X.Y. Ge G.B. Liu Y. Zhang Y.Y. Yang L. Sun H.Z. Structure-inhibition relationship of ginsenosides towards UDP-glucuronosyltransferases (UGTs) Toxicol. Appl. Pharmacol. 2013 267 149 154 10.1016/j.taap.2012.12.019 23306165 · DOI
  52. [56]Liu X. Chen D.W. Wu X. Zhao Z.Y. Fu Z.W. Huang C.T. Ye L.X. Du Z. Yu Y. Fang Z.Z. The Inhibition of UDP-Glucuronosyltransferase (UGT) Isoforms by Praeruptorin A and B Phytother. Res. 2016 30 1872 1878 10.1002/ptr.5697 27534594 · DOI
  53. [57]Liu X. Cao Y.F. Ran R.X. Dong P.P. Gonzalez F.J. Wu X. Huang T. Chen J.X. Fu Z.W. Li R.S. New insights into the risk of phthalates: Inhibition of UDP-glucuronosyltransferases Chemosphere 2016 144 1966 1972 10.1016/j.chemosphere.2015.10.076 26547877 PMC6300982 · DOI
  54. [59]Liu X. Cao Y.F. Dong P.P. Zhu L.L. Zhao Z.Y. Wu X. Fu Z.W. Huang C.T. Fang Z.Z. Sun H.Z. The inhibition of UDP-glucuronosyltransferases (UGTs) by vitamin A Xenobiotica 2017 47 376 381 10.1080/00498254.2016.1198841 27359323 · DOI

Cited by

Sorted by citations

Authors
Sun, D., Zhang, C.-Z., Ran, R.-X., Cao, Y.-F., Du, Z., Fu, Z.-W., Huang, C.-T., Zhao, Z.-Y., Zhang, W.-H., & Fang, Z.-Z.
Affiliations
  • Nankai University (CN)
  • Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin 300121, China
  • Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnosis, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China
  • Key Laborotary of Liaoning Tumor Clinical Metabolomics (KLLTCM), Jinzhou 121001, Liaoning, China
  • Tianjin Medical University (CN)
  • Tianjin Union Medical Center, 190 Jieyuan Road, Hongqiao District, Tianjin 300121, China
Corresponding author
Fang, Zhong-Ze
ORCID
Venue
Molecules
Publisher
MDPI AG
Published
2017-06-16
Volume
22
Issue
6
Pages
1008
ISSN
1420-3049 (ISSN-L)
DOI
10.3390/molecules22061008
PMC
PMC6152678
OpenAlex
W2626738390
Cited by
15
References
2
Citations by year
2025: 1 · 2021: 3 · 2019: 3 · 2018: 8
FWCI
4.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecules (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • China Postdoctoral Science Foundation (2016M590210)
  • National Key Research and Development Program of China (2016YFC0903100, 2016YFC0903102)
  • Thousand Young Talents Program of China
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Mangiferin and Mango Extracts
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
mangiferin, norathyriol, UDP-glucuronosyltransferase, UGT1A3, UGT1A7, UGT1A9, enzyme inhibition, competitive inhibition, herb-drug interactions, glucuronidation, 4-methylumbelliferone, mango, molecular docking, binding free energy
MeSH terms
Isoenzymes, Glucuronosyltransferase, Xanthenes, Herb-Drug Interactions, Xanthones

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