Inhibitory Effects of , , , and Extracts and Constituents on Human Liver Glucuronidation Activity

Overview

Journal Pharmacogn Mag

Publisher Sage Publications

Date 2017 Aug 16

PMID 28808386

Citations 3

Authors

Zulhilmi Husni

Sabariah Ismail

Mohd Halimhilmi Zulkiffli

Atiqah Afandi

Munirah Haron

Affiliations

Soon will be listed here.

Abstract

Background: , , and are commonly consumed as herbal medicines. However their effects on human liver glucuronidation activity are not yet evaluated.

Objective: In this study, we evaluate the inhibitory Effects of Andrographis paniculata, Gynura procumbens, Ficus deltoidea and Curcuma xanthorrhiza extracts and their constituents on human liver glucuronidation activity.

Materials And Methods: Herbal extracts (aqueous, methanolic and ethanolic extracts) and their constituents were incubated with human liver microsomes with the addition of UDPGA to initiate the reaction. Working concentrations of herbal extracts and their constituents ranged from 10 μg/mL to 1000 μg/mL and 10 μM to 300 μM respectively. IC50 was determined by monitoring the decrement of glucuronidation activity with the increment of herbal extracts or phytochemical constituent's concentrations.

Results: All herbal extracts inhibited human liver glucuronidation activity in range of 34.69 μg/mL to 398.10 μg/mL whereas for the constituents, only xanthorrhizol and curcumin (constituents of ) inhibited human liver glucuronidation activity with IC50 of 538.50 and 32.26 μM respectively.

Conclusion: In the present study, we have proved the capabilities of , , and to interfere with glucuronidation process in human liver microsomes.

Summary: This study documented the capabilities of , , and to inhibit human liver glucuronidation activity which may affect the metabolism of therapeutic drugs or hazardous toxicants that follow the same glucuronidation pathway. UGT: Uridine 5'-diphospho-glucuronosyltransferase; 4-MU: 4-methylumbelliferone; IC50: Half Maximal Inhibitory Concentration; Km: Michaelis constant; Vmax: Maximum velocity.

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References

Court M . Isoform-selective probe substrates for in vitro studies of human UDP-glucuronosyltransferases. Methods Enzymol. 2006; 400:104-16. DOI: 10.1016/S0076-6879(05)00007-8. View

Meyer U . Overview of enzymes of drug metabolism. J Pharmacokinet Biopharm. 1996; 24(5):449-59. DOI: 10.1007/BF02353473. View

Mahmud Z, Bachar S, Qais N . Antioxidant and Hepatoprotective Activities of Ethanolic Extracts of Leaves of Premna esculenta Roxb. against Carbon Tetrachloride-Induced Liver Damage in Rats. J Young Pharm. 2013; 4(4):228-34. PMC: 3573374. DOI: 10.4103/0975-1483.104366. View

Uchaipichat V, Mackenzie P, Guo X, Gardner-Stephen D, Galetin A, Houston J . Human udp-glucuronosyltransferases: isoform selectivity and kinetics of 4-methylumbelliferone and 1-naphthol glucuronidation, effects of organic solvents, and inhibition by diclofenac and probenecid. Drug Metab Dispos. 2004; 32(4):413-23. DOI: 10.1124/dmd.32.4.413. View

Caceres D, Hancke J, Burgos R, Wikman G . Prevention of common colds with Andrographis paniculata dried extract. A Pilot double blind trial. Phytomedicine. 2012; 4(2):101-4. DOI: 10.1016/S0944-7113(97)80051-7. View

Chen J, Lin H, Hu M . Metabolism of flavonoids via enteric recycling: role of intestinal disposition. J Pharmacol Exp Ther. 2003; 304(3):1228-35. DOI: 10.1124/jpet.102.046409. View

Chang R, Yeung H . Inhibition of growth of human immunodeficiency virus in vitro by crude extracts of Chinese medicinal herbs. Antiviral Res. 1988; 9(3):163-75. DOI: 10.1016/0166-3542(88)90001-0. View

Haron M, Ismail S . Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5'-diphospho-glucuronosyltransferase isoforms. Pharmacognosy Res. 2015; 7(4):341-9. PMC: 4660513. DOI: 10.4103/0974-8490.159580. View

Desai A, Innocenti F, Ratain M . UGT pharmacogenomics: implications for cancer risk and cancer therapeutics. Pharmacogenetics. 2003; 13(8):517-23. DOI: 10.1097/01.fpc.0000054116.14659.e5. View

10.

Ismail S, Hanapi N, Ab Halim M, Uchaipichat V, Mackenzie P . Effects of Andrographis paniculata and Orthosiphon stamineus extracts on the glucuronidation of 4-methylumbelliferone in human UGT isoforms. Molecules. 2010; 15(5):3578-92. PMC: 6263374. DOI: 10.3390/molecules15053578. View

11.

Mohamed M, Frye R . Inhibition of intestinal and hepatic glucuronidation of mycophenolic acid by Ginkgo biloba extract and flavonoids. Drug Metab Dispos. 2009; 38(2):270-5. DOI: 10.1124/dmd.109.030080. View

12.

Hoehle S, Pfeiffer E, Metzler M . Glucuronidation of curcuminoids by human microsomal and recombinant UDP-glucuronosyltransferases. Mol Nutr Food Res. 2007; 51(8):932-8. DOI: 10.1002/mnfr.200600283. View

13.

Mackenzie P, Bock K, Burchell B, Guillemette C, Ikushiro S, Iyanagi T . Nomenclature update for the mammalian UDP glycosyltransferase (UGT) gene superfamily. Pharmacogenet Genomics. 2005; 15(10):677-85. DOI: 10.1097/01.fpc.0000173483.13689.56. View

14.

Mohamed M, Frye R . Effects of herbal supplements on drug glucuronidation. Review of clinical, animal, and in vitro studies. Planta Med. 2010; 77(4):311-21. DOI: 10.1055/s-0030-1250457. View

15.

Hatcher H, Planalp R, Cho J, Torti F, Torti S . Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci. 2008; 65(11):1631-52. PMC: 4686230. DOI: 10.1007/s00018-008-7452-4. View

16.

Pan M, Huang T, Lin J . Biotransformation of curcumin through reduction and glucuronidation in mice. Drug Metab Dispos. 1999; 27(4):486-94. View

17.

Hanioka N, Jinno H, Tanaka-Kagawa T, Nishimura T, Ando M . Determination of UDP-glucuronosyltransferase UGT1A6 activity in human and rat liver microsomes by HPLC with UV detection. J Pharm Biomed Anal. 2001; 25(1):65-75. DOI: 10.1016/s0731-7085(00)00491-x. View

18.

Sardesai V . Herbal medicines: poisons or potions?. J Lab Clin Med. 2002; 139(6):343-8. DOI: 10.1067/mlc.2002.124582. View

19.

Mohamed M, Frye R . Inhibitory effects of commonly used herbal extracts on UDP-glucuronosyltransferase 1A4, 1A6, and 1A9 enzyme activities. Drug Metab Dispos. 2011; 39(9):1522-8. PMC: 3164271. DOI: 10.1124/dmd.111.039602. View

20.

Donato M, Montero S, Castell J, Gomez-Lechon M, Lahoz A . Validated assay for studying activity profiles of human liver UGTs after drug exposure: inhibition and induction studies. Anal Bioanal Chem. 2010; 396(6):2251-63. DOI: 10.1007/s00216-009-3441-1. View