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Drug Metabolism and Bioanalysis Letters

Editor-in-Chief

ISSN (Print): 2949-6810
ISSN (Online): 2949-6829

Research Article

In Vitro Inhibitory Effects of Agarwood Tea (Aquilaria malaccensis Lamk) Aqueous Extract on Human Cytochrome P450 (CYP) Enzyme Activities

Author(s): Pan Yan*, Ung Yee Tze, Premika A/P R Jagadish, Lim Kuan Hon, Lamia Noushin Sadeque Chowdhury, Shang Tao and Ong Chin Eng

Volume 15, Issue 3, 2022

Published on: 19 September, 2022

Page: [178 - 191] Pages: 14

DOI: 10.2174/1872312815666220707114744

Price: $65

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Abstract

Background: Agarwood tea derived from Aquilaria malaccensis Lamk is becoming an increasingly popular herbal drink that is said to have multiple health benefits. Co-administration of this tea and clinical used drugs is possible, but it increases the risk of drug-herb interactions.

Objective: This in vitro study investigated the inhibitory effects of agarwood tea aqueous extract on the eight major human drug-metabolising cytochrome P450 (CYP) enzyme activities.

Methods: High-throughput fluorescence-based Vivid® CYP450 screening kits were employed to obtain the enzyme activities before and after incubation with agarwood tea aqueous extract.

Results: Agarwood aqueous extract potently inhibited CYP2C9, CYP2D6, and CYP3A4 activities with Ki values of 5.1, 34.5, and 20.3μg/ml, respectively. The most likely inhibition mode responsible for these inhibitions was non-competitive inhibition. On the other hand, at 1000μg/ml, agarwood tea aqueous extract negligibly inhibited CYP1A2, CYP2B6, CYP2C19, CYP2E1, and CYP3A5 activities.

Conclusion: These findings can be used to design additional in vitro investigations using clinical relevant drug substrates for CYP2C9, CYP2D6, and CYP3A4. Subsequently, future studies can be conducted to determine potential interactions between agarwood tea aqueous extract and CYP using in vivo models.

Keywords: Agarwood tea, Aquilaria malaccensis, cytochrome P450, CYP, drug-herb interactions, enzyme inhibition.

Graphical Abstract

[1]
Wegener, T. Patterns and trends in the use of herbal products, herbal medicine and herbal medicinal products. Int. J. Complement. Altern. Med., 2017, 9(6)
[http://dx.doi.org/10.15406/ijcam.2017.09.00317]
[2]
Wegener, T.; Deitelhoff, B.; Silber-Mankowsky, A. Drug safety aspects of herbal medicinal products. Wien. Med. Wochenschr., 2015, 165(11-12), 243-250.
[http://dx.doi.org/10.1007/s10354-015-0370-9] [PMID: 26183727]
[3]
Brown, A.C. Liver toxicity related to herbs and dietary supplements: Online table of case reports. Part 2 of 5 series. Food Chem. Toxicol., 2017, 107(Pt A), 472-501.
[http://dx.doi.org/10.1016/j.fct.2016.07.001] [PMID: 27402097]
[4]
Zheng, E.X.; Navarro, V.J. Liver injury from herbal, dietary, and weight loss supplements: A review. J. Clin. Transl. Hepatol., 2015, 3(2), 93-98.
[http://dx.doi.org/10.14218/JCTH.2015.00006] [PMID: 26357638]
[5]
Ghiculesco, R. Abnormal laboratory results: Therapeutic drug monitoring: Which drugs, why, when and how to do it. Aust. Prescr., 2008, 31(2), 42-44.
[http://dx.doi.org/10.18773/austprescr.2008.025]
[6]
Parveen, A.; Parveen, B.; Parveen, R.; Ahmad, S. Challenges and guidelines for clinical trial of herbal drugs. J. Pharm. Bioallied Sci., 2015, 7(4), 329-333.
[http://dx.doi.org/10.4103/0975-7406.168035] [PMID: 26681895]
[7]
Bhat, S. Challenges in the regulation of Traditional Medicine–a review of global scenario. J. Ayurveda Holist. Med., 2015, 3(4), 110-120.
[8]
Zuo, Z.; Huang, M.; Kanfer, I.; Chow, M.S.S.; Cho, W.C.S. Herb-Drug Interactions ; Systematic Re-view, Mechanisms, and Therapies, 2015.
[9]
Cho, H; Yoon, I Pharmacokinetic interactions of herbs with cytochrome P450 and P-glycoprotein. Evidence-Based Complement Altern. Med., 2015, 2015
[10]
Fasinu, P.S.; Bouic, P.J.; Rosenkranz, B. An overview of the evidence and mechanisms of herb-drug interactions. Front. Pharmacol., 2012, 3, 69.
[http://dx.doi.org/10.3389/fphar.2012.00069] [PMID: 22557968]
[11]
Haefeli, W.E.; Carls, A. Drug interactions with phytotherapeutics in oncology. Expert Opin. Drug Metab. Toxicol., 2014, 10(3), 359-377.
[http://dx.doi.org/10.1517/17425255.2014.873786] [PMID: 24387348]
[12]
Zanger, U.M.; Schwab, M. Cytochrome P450 enzymes in drug metabolism: Regulation of gene ex-pression, enzyme activities, and impact of genetic variation. Pharmacol. Ther., 2013, 138(1), 103-141.
[http://dx.doi.org/10.1016/j.pharmthera.2012.12.007] [PMID: 23333322]
[13]
Adam, A.Z.; Lee, S.Y.; Mohamed, R. Pharmacological properties of agarwood tea derived from Aquilaria (Thymelaeaceae) leaves: An emerging contemporary herbal drink. J. Herb. Med., 2017, 10, 37-44.
[http://dx.doi.org/10.1016/j.hermed.2017.06.002]
[14]
Hashim, Y.Z.H.Y.; Kerr, P.G.; Abbas, P.; Mohd Salleh, H. Aquilaria spp. (agarwood) as source of health beneficial compounds: A review of traditional use, phytochemistry and pharmacology. J. Ethnopharmacol., 2016, 189, 331-360.
[http://dx.doi.org/10.1016/j.jep.2016.06.055] [PMID: 27343768]
[15]
Muzafar, A.; Mokhtar, A.; Hanim, H.; Zain, M.; Ta, M.M. Overview of medicinal properties and tox-icities of agarwood species. Educ. J. Sci Math. Technol., 2021, 8(2), 1-16.
[16]
Šarić; Mustapić; D.; Debeljak, Ž.; Maleš, Ž.; Bojić; M. The inhibitory effect of flavonoid aglycones on the metabolic activity of CYP3A4 enzyme. Molecules, 2018, 23(10), 1-12.
[http://dx.doi.org/10.3390/molecules23102553] [PMID: 30301254]
[17]
Palacharla, R.C.; Uthukam, V.; Manoharan, A.; Ponnamaneni, R.K.; Padala, N.P.; Boggavarapu, R.K.; Bhyrapuneni, G.; Ajjala, D.R.; Nirogi, R. Inhibition of cytochrome P450 enzymes by saturated and unsaturated fatty acids in human liver microsomes, characterization of enzyme kinetics in the presence of bovine serum albumin (0.1 and 1.0% w/v) and in vitro - in vivo extrapolation of hepatic clearance. Eur. J. Pharm. Sci., 2017, 101, 80-89.
[http://dx.doi.org/10.1016/j.ejps.2017.01.027] [PMID: 28179134]
[18]
Ngui, W.T.S. Isolation, identification and bioactivity evaluation of mangiferin and genkwanin 5-O-β;-primeveroside in gaharu plant parts and finished products for gaharu technologies sdn bhd. MPhil the-sis; University of Nottingham, 2018.
[19]
Ozgenc, A. Vivid ® CYP450 Screening Kits User Guide. Available from: www.lifetechnologies.com (cited 2022 Feb 25)
[20]
Sharoen Lim, Y.M.; Alshagga, M.; Alshawsh, M.A.; Ong, C.E.; Yan, P. In vitro effects of 95% khat Ethanol Extract (KEE) on Human recombinant cytochrome P450 (CYP)1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2E1, CYP2J2, and CYP3A5. Drug Metab. Pers. Ther., 2021, 37(1), 55-67.
[21]
Lim, S.Y.M.; Athira, R.B.A.; Ung, Y.T.; Alshagga, M.; Mohammed, A.A.; Zahurin, M. Effect of 95% ethanol khat extract and cathinone on in vitro human activity. Eur. J. Drug Metab. Pharmacokinet., 2018, 450.
[PMID: 30306496]
[22]
de Ron, L; Rajaraman, G. Assessment of the Time-Dependent Inhibition (TDI) potential of test compounds with human liver microsomes by IC50 shift method using a nondilution approach. Curr. Protoc. Pharmacol., 2012, 58(1), 7.14.
[23]
Parkinson, A.; Kazmi, F.; Buckley, D.B.; Yerino, P.; Paris, B.L.; Holsapple, J.; Toren, P.; Otradovec, S.M.; Ogilvie, B.W. An evaluation of the dilution method for identifying metabolism-dependent in-hibitors of cytochrome P450 enzymes. Drug Metab. Dispos., 2011, 39(8), 1370-1387.
[http://dx.doi.org/10.1124/dmd.111.038596] [PMID: 21525169]
[24]
Waldrop, G.L. A qualitative approach to enzyme inhibition. Biochem. Mol. Biol. Educ., 2009, 37(1), 11-15.
[http://dx.doi.org/10.1002/bmb.20243] [PMID: 21567682]
[25]
Delaune, K.; Alsayouri, K. Physiology, noncompetitive inhibitor; StatPearls Publishing: Treasure Island (FL) 2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK545242/?report=classic (Accessed on 2021 Dec 22).
[26]
Wang, S.; Yu, Z.; Wang, C.; Wu, C.; Guo, P.; Wei, J. Chemical constituents and pharmacological ac-tivity of agarwood and Aquilaria plants. Molecules, 2018, 23(2), 1-21.
[http://dx.doi.org/10.3390/molecules23020342] [PMID: 29414842]
[27]
Gouws, C.; Hamman, J.H. What are the dangers of drug interactions with herbal medicines? Expert Opin. Drug Metab. Toxicol., 2020, 16(3), 165-167.
[http://dx.doi.org/10.1080/17425255.2020.1733969] [PMID: 32079422]
[28]
Kong, W.M.; Chik, Z.; Ramachandra, M.; Subramaniam, U.; Aziddin, R.E.; Mohamed, Z. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules, 2011, 16(9), 7344-7356.
[http://dx.doi.org/10.3390/molecules16097344] [PMID: 21876481]
[29]
Surjanto, B.R.; Hanum, T.; Pulungan, W. Phytochemical and antioxidant activity of gaharu leaf tea (Aquilaria malaccensis Lamk) as raw material of tea from middle Tapanuli Regency, North Sumatera Province Phytochemical and antioxidant activity of gaharu leaf tea (Aquilaria malaccensis Lamk). IPO Conf. Ser Earth Environ. Sci., 2019, 260, 012101.
[30]
Ito, T.; Kakino, M.; Tazawa, S.; Watarai, T.; Oyama, M.; Maruyama, H.; Araki, Y.; Hara, H.; Iinuma, M. Quantification of polyphenols and pharmacological analysis of water and ethanol-based extracts of cultivated agarwood leaves. J. Nutr. Sci. Vitaminol. Nutr. Sci. Vitaminol., 2012, 58(2), 136-142.
[http://dx.doi.org/10.3177/jnsv.58.136] [PMID: 22790572]
[31]
Zhang, Z.Y.; Wong, Y.N. Enzyme kinetics for clinically relevant CYP inhibition. Curr. Drug Metab., 2005, 6(3), 241-257.
[http://dx.doi.org/10.2174/1389200054021834] [PMID: 15975042]
[32]
Zhou, S.F.; Zhou, Z.W.; Yang, L.P.; Cai, J.P. Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr. Med. Chem., 2009, 16(27), 3480-3675.
[http://dx.doi.org/10.2174/092986709789057635] [PMID: 19515014]
[33]
Taylor, C.; Crosby, I.; Yip, V.; Maguire, P.; Pirmohamed, M.; Turner, R.M. A review of the important role of CYP2D6 in pharmacogenomics. Genes (Basel), 2020, 11(11), 1-22.
[http://dx.doi.org/10.3390/genes11111295] [PMID: 33143137]
[34]
Fuhr, L.M.; Marok, F.Z.; Hanke, N.; Selzer, D.; Lehr, T. Pharmacokinetics of the CYP3A4 and CYP2B6 inducer carbamazepine and its drug-drug interaction potential: A physiologically based pharmacokinetic modeling approach. Pharmaceutics, 2021, 13(2), 1-19.
[http://dx.doi.org/10.3390/pharmaceutics13020270] [PMID: 33671323]
[35]
Dhami, N.; Mishra, A. Phytochemical variation: How to resolve the quality controversies of herbal medicinal products? J. Herb. Med., 2015, 5(2), 118-127.
[http://dx.doi.org/10.1016/j.hermed.2015.04.002]
[36]
Abdullahi, A.; Tijjiani, A.; Abubakar, A.I.; Khairulmazmi, A.; Ismail, M.R. Chapter 17 - Plant biomolecule antimicrobials: An alternative control measures for food security and safety. In: Herbal Biomolecules in Healthcare Applications; , 2022; pp. 381-406.

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