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Current Pharmaceutical Analysis

Editor-in-Chief

ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Research Article

Determination of Main Compositions in Phyllanthus Urinaria and its Effects on Cyp450 in Rats

Author(s): Zhennan Zhang, Zhe Sun, Yaozhen Ye and Xianqin Wang*

Volume 16, Issue 5, 2020

Page: [520 - 528] Pages: 9

DOI: 10.2174/1573412915666190312160359

Price: $65

Abstract

Background: Phyllanthus urinaria, a traditional herbal medicine, has aroused widespread concern at home and abroad. However, there are few studies on the effects of Phyllanthus urinaria on CYP450. Therefore, this study aims to explore the main chemical compositions of Phyllanthus urinaria and its effect on the activity of CYP450 enzyme in rats.

Methods: Acetonitrile and 0.1% Trifluoroacetic Acid (TFA) were used as mobile phase, along with the application of gradient elution to simultaneously determine the main chemical constituents in Phyllanthus urinaria by HPLC (r2>0.999). Sprague-Dawley (SD) rats, randomly divided into control group, low-dose group and high-dose group, were treated with normal saline and different doses of Phyllanthus urinaria extract solution, respectively. Additionally, the rats were given intragastric administration of cocktail probe (specific substrates of CYP450 isoenzyme) at 15th day; the plasma was collected by tail vein at various times. Furthermore, the UPLC-MS/MS method (r2>0.99) was used to detect the probe concentration, along with the evaluation of the activity of CYP450 enzyme according to the pharmacokinetic parameters of the probe.

Results: Gallic acid, 3, 4-dihydroxybenzoic acid, caffeic acid, corilagin and ellagic acid were found in the Phyllanthus urinaria extract solution by HPLC. Compared with the control group, the metabolism of bupropion, metoprolol, midazolam and tolbutamide slowed down significantly in the Phyllanthus urinaria group, with no significant metabolic changes in phenacetin.

Conclusion: Phyllanthus urinaria could induce activity of CYP2D6, CYP2B1, CYP3A4 and CYP2C9, without exerting a significant effect on CYP1A2.

Keywords: Phyllanthus urinaria, HPLC, UPLC-MS/MS, cocktail, CYP450, gallic acid.

Graphical Abstract

[1]
Thyagarajan, S.P.; Subramanian, S.; Thirunalasundari, T.; Venkateswaran, P.S.; Blumberg, B.S. Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. Lancet, 1988, 2(8614), 764-766.
[http://dx.doi.org/10.1016/S0140-6736(88)92416-6] [PMID: 2901611]
[2]
Funatogawa, K.; Hayashi, S.; Shimomura, H.; Yoshida, T.; Hatano, T.; Ito, H.; Hirai, Y. Antibacterial activity of hydrolyzable tannins derived from medicinal plants against Helicobacter pylori. Microbiol. Immunol., 2004, 48(4), 251-261.
[http://dx.doi.org/10.1111/j.1348-0421.2004.tb03521.x] [PMID: 15107535]
[3]
Ko, H. Geraniin inhibits TGF-β1-induced epithelial-mesenchymal transition and suppresses A549 lung cancer migration, invasion and anoikis resistance. Bioorg. Med. Chem. Lett., 2015, 25(17), 3529-3534.
[http://dx.doi.org/10.1016/j.bmcl.2015.06.093] [PMID: 26169124]
[4]
Londhe, J.S.; Devasagayam, T.P.A.; Foo, L.Y.; Shastry, P.; Ghaskadbi, S.S. Geraniin and amariin, ellagitannins from Phyllanthus amarus, protect liver cells against ethanol induced cytotoxicity. Fitoterapia, 2012, 83(8), 1562-1568.
[http://dx.doi.org/10.1016/j.fitote.2012.09.003] [PMID: 22982332]
[5]
Lewis, D.F.; Dickins, M. Baseline lipophilicity relationships in human cytochromes P450 associated with drug metabolism. Drug Metab. Rev., 2003, 35(1), 1-18.
[http://dx.doi.org/10.1081/DMR-120018245] [PMID: 12635813]
[6]
Pelkonen, O. Human CYPs: in vivo and clinical aspects. Drug Metab. Rev., 2002, 34(1-2), 37-46.
[http://dx.doi.org/10.1081/DMR-120001388] [PMID: 11996010]
[7]
Danton, A.C.; Montastruc, F.; Sommet, A.; Durrieu, G.; Bagheri, H.; Bondon-Guitton, E.; Lapeyre-Mestre, M.; Montastruc, J.L. Importance of cytochrome P450 (CYP450) in adverse drug reactions due to drug-drug interactions: a PharmacoVigilance study in France. Eur. J. Clin. Pharmacol., 2013, 69(4), 885-888.
[http://dx.doi.org/10.1007/s00228-012-1394-3] [PMID: 22996074]
[8]
Nelson, D.R.; Koymans, L.; Kamataki, T.; Stegeman, J.J.; Feyereisen, R.; Waxman, D.J.; Waterman, M.R.; Gotoh, O.; Coon, M.J.; Estabrook, R.W.; Gunsalus, I.C.; Nebert, D.W. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics, 1996, 6(1), 1-42.
[http://dx.doi.org/10.1097/00008571-199602000-00002] [PMID: 8845856]
[9]
Wrighton, S.A.; VandenBranden, M.; Ring, B.J. The human drug metabolizing cytochromes P450. J. Pharmacokinet. Biopharm., 1996, 24(5), 461-473.
[http://dx.doi.org/10.1007/BF02353474] [PMID: 9131485]
[10]
Izzo, A.A.; Ernst, E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs, 2009, 69(13), 1777-1798.
[http://dx.doi.org/10.2165/11317010-000000000-00000] [PMID: 19719333]
[11]
Williamson, E.M. Drug interactions between herbal and prescription medicines. Drug Saf., 2003, 26(15), 1075-1092.
[http://dx.doi.org/10.2165/00002018-200326150-00002] [PMID: 14640772]
[12]
Breimer, D.D. Interindividual variations in drug disposition. Clinical implications and methods of investigation. Clin. Pharmacokinet., 1983, 8(5), 371-377.
[http://dx.doi.org/10.2165/00003088-198308050-00001] [PMID: 6627809]
[13]
Breimer, D.D.; Schellens, J.H.A. A ‘cocktail’ strategy to assess in vivo oxidative drug metabolism in humans. Trends Pharmacol. Sci., 1990, 11(6), 223-225.
[http://dx.doi.org/10.1016/0165-6147(90)90245-4] [PMID: 2200179]
[14]
Ryu, J.Y.; Song, I.S.; Sunwoo, Y.E.; Shon, J.H.; Liu, K.H.; Cha, I.J.; Shin, J.G. Development of the “Inje cocktail” for high-throughput evaluation of five human cytochrome P450 isoforms in vivo. Clin. Pharmacol. Ther., 2007, 82(5), 531-540.
[http://dx.doi.org/10.1038/sj.clpt.6100187] [PMID: 17392720]
[15]
Blakey, G.E.; Lockton, J.A.; Perrett, J.; Norwood, P.; Russell, M.; Aherne, Z.; Plume, J. Pharmacokinetic and pharmacodynamic assessment of a five-probe metabolic cocktail for CYPs 1A2, 3A4, 2C9, 2D6 and 2E1. Br. J. Clin. Pharmacol., 2004, 57(2), 162-169.
[http://dx.doi.org/10.1046/j.1365-2125.2003.01973.x] [PMID: 14748815]
[16]
Otten, J.N.; Hingorani, G.P.; Hartley, D.P.; Kragerud, S.D.; Franklin, R.B. An in vitro, high throughput, seven CYP cocktail inhibition assay for the evaluation of new chemical entities using LC-MS/MS. Drug Metab. Lett., 2011, 5(1), 17-24.
[http://dx.doi.org/10.2174/187231211794455235] [PMID: 21198441]
[17]
Pillai, V.C.; Strom, S.C.; Caritis, S.N.; Venkataramanan, R. A sensitive and specific CYP cocktail assay for the simultaneous assessment of human cytochrome P450 activities in primary cultures of human hepatocytes using LC-MS/MS. J. Pharm. Biomed. Anal., 2013, 74, 126-132.
[18]
Wang, S.; Wang, Z.; Chen, D.; Chen, M.; Lin, Y.; Liu, Z.; Zhang, L.; Wen, C.; Wang, X.; Ma, J. Effect of acute paraquat poisoning on CYP450 isoforms activity in rats by cocktail method. Int. J. Clin. Exp. Med., 2015, 8(10), 19100-19106.
[PMID: 26770539]
[19]
Ma, J.; Wang, S.; Zhang, M.; Zhang, Q.; Zhou, Y.; Lin, C.; Lin, G.; Wang, X. Simultaneous determination of bupropion, metroprolol, midazolam, phenacetin, omeprazole and tolbutamide in rat plasma by UPLC-MS/MS and its application to cytochrome P450 activity study in rats. Biomed. Chromatogr., 2015, 29(8), 1203-1212.
[http://dx.doi.org/10.1002/bmc.3409] [PMID: 25582505]
[20]
Cheng, J.J.; Yang, N.B.; Wu, L.; Lin, J.L.; Dai, G.X.; Zhu, J.Y. Effects of zedoary turmeric oil on P450 activities in rats with liver cirrhosis induced by thioacetamide. Int. J. Clin. Exp. Pathol., 2014, 7(11), 7854-7862.
[PMID: 25550825]
[21]
Wang, X.; Chen, M.; Chen, X.; Ma, J.; Wen, C.; Pan, J.; Hu, L.; Lin, G. The effects of acute hydrogen sulfide poisoning on cytochrome P450 isoforms activity in rats. BioMed Res. Int., 2014, 2014 209393
[http://dx.doi.org/10.1155/2014/209393]
[22]
Zhang, Y.; Ding, T.; Diao, T.; Deng, M.; Chen, S. Effects of Polygonum multiflorum on the activity of cytochrome P450 isoforms in rats. Pharmazie, 2015, 70(1), 47-54.
[PMID: 25975098]
[23]
Athukuri, B.L.; Neerati, P. Enhanced oral bioavailability of metoprolol with gallic acid and ellagic acid in male Wistar rats: involvement of CYP2D6 inhibition. Drug Metab. Pers. Ther., 2016, 31(4), 229-234.
[http://dx.doi.org/10.1515/dmpt-2016-0029] [PMID: 27875319]
[24]
Rastogi, H.; Jana, S. Evaluation of inhibitory effects of caffeic acid and quercetin on human liver cytochrome p450 activities. Phytother. Res., 2014, 28(12), 1873-1878.
[http://dx.doi.org/10.1002/ptr.5220] [PMID: 25196644]
[25]
Zhang, Z.; Hamilton, S.M.; Stewart, C.; Strother, A.; Teel, R.W. Inhibition of liver microsomal cytochrome P450 activity and metabolism of the tobacco-specific nitrosamine NNK by capsaicin and ellagic acid. Anticancer Res., 1993, 13(6A), 2341-2346.
[PMID: 8297156]
[26]
Pu, Q.H.; Shi, L.; Yu, C. Time-dependent inhibition of CYP3A4 by gallic acid in human liver microsomes and recombinant systems. Xenobiotica, 2015, 45(3), 213-217.
[http://dx.doi.org/10.3109/00498254.2014.973470] [PMID: 25322914]
[27]
Krajka-Kuźniak, V.; Szaefer, H.; Baer-Dubowska, W. Modulation of 3-methylcholanthrene-induced rat hepatic and renal cytochrome P450 and phase II enzymes by plant phenols: protocatechuic and tannic acids. Toxicol. Lett., 2004, 152(2), 117-126.
[PMID: 15302093]

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