Potential Pharmacokinetic Herb-Drug Interactions: Have we Overlooked the Importance of Human Carboxylesterases 1 and 2?

Author(s): Jing Xu, Jin-Chun Qiu, Xing Ji, Hong-Li Guo, Xuan Wang, Bo Zhang*, Tengfei Wang, Feng Chen*.

Journal Name: Current Drug Metabolism

Volume 20 , Issue 2 , 2019

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Abstract:

Background: Herbal products have grown steadily across the globe and have increasingly been incorporated into western medicine for healthcare aims, thereby causing potential pharmacokinetic Herb-drug Interactions (HDIs) through the inhibition or induction of drug-metabolizing enzymes and transporters. Human Carboxylesterases 1 (CES1) and 2 (CES2) metabolize endogenous and exogenous chemicals including many important therapeutic medications. The growing number of CES substrate drugs also underscores the importance of the enzymes. Herein, we summarized those potential inhibitors and inducers coming from herbal constituents toward CES1 and CES2. We also reviewed the reported HDI studies focusing on herbal products and therapeutic agents metabolized by CES1 or CES2.

Methods: We searched in PubMed for manuscript published in English after Jan 1, 2000 combining terms “carboxylesterase 1”, “carboxylesterase 2”, “inhibitor”, “inducer”, “herb-drug interaction”, “inhibitory”, and “herbal supplement”. We also searched specific websites including FDA and EMA. The data of screened papers were analyzed and summarized.

Results: The results showed that more than 50 natural inhibitors of CES1 or CES2, including phenolic chemicals, triterpenoids, and tanshinones were found from herbs, whereas only few inducers of CES1 and CES2 were reported. Systemic exposure to some commonly used drugs including oseltamivir, irinotecan, and clopidogrel were changed when they were co-administered with herb products such as goldenseal, black cohosh, ginger, St. John’s Wort, curcumin, and some Chinese compound formula in animals.

Conclusion: Nonclinical and clinical studies on HDIs are warranted in the future to provide safety information toward better clinical outcomes for the combination of herbal products and conventional drugs.

Keywords: Carboxylesterase (CES), CES1, CES2, herb-drug interactions, pharmacokinetics, herbal components.

[1]
Gardiner, P.; Graham, R.E.; Legedza, A.T.R.; Eisenberg, D.M.; Phillips, R.S. Factors associated with dietary supplement use among prescription medication users. Arch. Intern. Med., 2006, 166(18), 1968-1974.
[2]
Bent, S. Herbal medicine in the United States: Review of efficacy, safety, and regulation: grand rounds at University of California, San Francisco Medical Center. J. Gen. Intern. Med., 2008, 23(6), 854-859.
[3]
Brantley, S.J.; Argikar, A.A.; Lin, Y.S.; Nagar, S.; Paine, M.F. Herb-drug interactions: challenges and opportunities for improved predictions. Drug Metab. Dispos., 2014, 42(3), 301-317.
[4]
Tyler, S.K.K.; Eckl, V.; Morton, C.; Stredney, R. Herbal supplement sales in US increase 7.7% in 2016. HerbalGram, 2017, 115, 56-65.
[5]
Scripture, C.D.; Figg, W.D. Drug interactions in cancer therapy. Nat. Rev. Cancer, 2006, 6(7), 546-558.
[6]
Dresser, G.K.; Bailey, D.G. A basic conceptual and practical over-view of interactions with highly prescribed drugs. Can. J. Clin. Pharmacol., 2002, 9(4), 191-198.
[7]
Holmes, R.S.; Cox, L.A.; VandeBerg, J.L. Mammalian carboxy- lesterase 3: Comparative genomics and proteomics. Genetica, 2010, 138(7), 695-708.
[8]
Satoh, T.; Hosokawa, M. The mammalian carboxylesterases: from molecules to functions. Annu. Rev. Pharmacol. Toxicol., 1998, 38, 257-288.
[9]
Hosokawa, M.; Furihata, T.; Yaginuma, Y.; Yamamoto, N.; Koy-ano, N.; Fujii, A.; Nagahara, Y.; Satoh, T.; Chiba, K. Genomic structure and transcriptional regulation of the rat, mouse, and human carboxylesterase genes. Drug Metab. Rev., 2007, 39(1), 1-15.
[10]
Hosokawa, M. Structure and catalytic properties of carboxyles- terase isozymes involved in metabolic activation of prodrugs. Molecules, 2008, 13(2), 412-431.
[11]
Satoh, T.; Hosokawa, M. Structure, function and regulation of carboxylesterases. Chem. Biol. Interact., 2006, 162(3), 195-211.
[12]
Imai, T.; Hosokawa, M. Prodrug approach using carboxylesterases activity: Catalytic properties and gene regulation of carboxyles- terase in mammalian tissue. J. Pestic. Sci., 2010, 35(3), 229-239.
[13]
Laizure, S.C.; Herring, V.; Hu, Z.; Witbrodt, K.; Parker, R.B. The role of human carboxylesterases in drug metabolism: Have we over-looked their importance? Pharmacotherapy, 2013, 33(2), 210-222.
[14]
Sprouse, A.A.; Van Breemen, R.B. Pharmacokinetic interactions between drugs and botanical dietary supplements. Drug Metab. Dispos., 2016, 44(2), 162-171.
[15]
Chen, F.; Wen, Q.; Jiang, J.; Li, H.L.; Tan, Y.F.; Li, Y.H.; Zeng, N.K. Could the gut microbiota reconcile the oral bioavailability conundrum of traditional herbs? J. Ethnopharmacol., 2016, 179, 253-264.
[16]
Sun, D.X.; Ge, G.B.; Dong, P.P.; Cao, Y.F.; Fu, Z.W.; Ran, R.X.; Wu, X.; Zhang, Y.Y.; Hua, H.M.; Zhao, Z.; Fang, Z.Z. Inhibition behavior of Fructus Psoraleae’s ingredients towards human carboxyl-esterase 1 (hCES1). Xenobiotica, 2016, 46(6), 503-510.
[17]
Li, Y.G.; Hou, J.; Li, S.Y.; Lv, X.; Ning, J.; Wang, P.; Liu, Z.M.; Ge, G.B.; Ren, J.Y.; Yang, L. Fructus Psoraleae contains natural compounds with potent inhibitory effects towards human carboxyl-esterase 2. Fitoterapia, 2015, 101, 99-106.
[18]
Liu, Y.J.; Li, S.Y.; Hou, J.; Liu, Y.F.; Wang, D.D.; Jiang, Y.S.; Ge, G.B.; Liang, X.M.; Yang, L. Identification and characterization of naturally occurring inhibitors against human carboxylesterase 2 in White Mulberry Root-bark. Fitoterapia, 2016, 115, 57-63.
[19]
Wang, A.H.; Huo, X.K.; Feng, L.; Sun, C.P.; Deng, S.; Zhang, H.L.; Zhang, B.J.; Ma, X.C.; Jia, J.M.; Wang, C. Phenolic glycosides and monoterpenoids from the roots of Euphorbia ebracteolata and their bioactivities. Fitoterapia, 2017, 121, 175-182.
[20]
Mai, Z.P.; Zhou, K.; Ge, G.B.; Wang, C.; Huo, X.K.; Dong, P.P.; Deng, S.; Zhang, B.J.; Zhang, H.L.; Huang, S.S.; Ma, X.C. Protostane triterpenoids from the rhizome of alisma orientale exhibit inhibitory effects on human carboxylesterase 2. J. Nat. Prod., 2015, 78(10), 2372-2380.
[21]
Zou, L.W.; Li, Y.G.; Wang, P.; Zhou, K.; Hou, J.; Jin, Q.; Hao, D.C.; Ge, G.B.; Yang, L. Design, synthesis, and structure-activity relationship study of glycyrrhetinic acid derivatives as potent and selective inhibitors against human carboxylesterase 2. Eur. J. Med. Chem., 2016, 112, 280-288.
[22]
Zou, L.W.; Dou, T.Y.; Wang, P.; Lei, W.; Weng, Z.M.; Hou, J.; Wang, D.D.; Fan, Y.M.; Zhang, W.D.; Ge, G.B.; Yang, L. Structure-activity relationships of pentacyclic triterpenoids as potent and selective inhibitors against human carboxylesterase 1. Front. Pharmacol., 2017, 8, 435.
[23]
Yuan, W.J.; Ding, X.; Wang, Z.; Yang, B.J.; Li, X.N.; Zhang, Y.; Chen, D.Z.; Li, S.L.; Chen, Q.; Di, Y.T.; Aisa, H.A.; Hao, X.J. Two novel diterpenoid heterodimers, bisebracteolasins A and B, from euphorbia ebracteolata hayata, and the cancer chemotherapeutic potential of bisebracteolasin A. Sci. Rep., 2017, 7(1), 14507.
[24]
Hatfield, M.J.; Tsurkan, L.G.; Hyatt, J.L.; Edwards, C.C.; Lemoff, A.; Jeffries, C.; Yan, B.; Potter, P.M. Modulation of esterified drug metabolism by tanshinones from Salvia miltiorrhiza (“Danshen”). J. Nat. Prod., 2013, 76(1), 36-44.
[25]
Lee, J.H.; Shin, Y.J.; Kim, H.J.; Oh, J.H.; Jang, Y.P.; Lee, Y.J. Danshen extract does not alter pharmacokinetics of docetaxel and clopidogrel, reflecting its negligible potential in P-glycoprotein and cytochrome P4503A-mediated herb-drug interactions. Int. J. Pharm., 2011, 410(1-2), 68-74.
[26]
Crow, J.A.; Herring, K.L.; Xie, S.; Borazjani, A.; Potter, P.M.; Ross, M.K. Inhibition of carboxylesterase activity of THP1 mono- cytes/macrophages and recombinant human carboxylesterase 1 by oxysterols and fatty acids. Biochim. Biophys. Acta, 2010, 1801(1), 31-41.
[27]
Xu, J.; Yin, L.; Xu, Y.; Li, Y.; Zalzala, M.; Cheng, G.; Zhang, Y. Hepatic carboxylesterase 1 is induced by glucose and regulates postprandial glucose levels. PLoS One, 2014, 9(10), e109663.
[28]
Chen, Y.T.; Shi, D.; Yang, D.; Yan, B. Antioxidant sulforaphane and sensitizer trinitrobenzene sulfonate induce carboxylesterase-1 through a novel element transactivated by nuclear factor-E2 related factor-2. Biochem. Pharmacol., 2012, 84(6), 864-871.
[29]
Fahey, J.W.; Wade, K.L.; Wehage, S.L.; Holtzclaw, W.D.; Liu, H.; Talalay, P.; Fuchs, E.; Stephenson, K.K. Stabilized sulforaphane for clinical use: Phytochemical delivery efficiency. Mol. Nutr. Food Res., 2017, 61(4), 1600766.
[30]
Liu, R.; Tam, T.W.; Mao, J.; Saleem, A.; Krantis, A.; Arnason, J.T.; Foster, B.C. The effect of natural health products and traditional medicines on the activity of human hepatic microsomal- mediated metabolism of oseltamivir. J. Pharm. Pharm. Sci., 2010, 13(1), 43-55.
[31]
Gorman, G.S.; Coward, L.; Darby, A.; Rasberry, B. Effects of herbal supplements on the bioactivation of chemotherapeutic agents. J. Pharm. Pharmacol., 2013, 65(7), 1014-1025.
[32]
Trana, C.; Toth, G.; Wijns, W.; Barbato, E.St. John’s Wort in patients non-responders to clopidogrel undergoing percutaneous coronary intervention: A single-center randomized open-label trial (St. John’s Trial). J. Cardiovasc. Transl. Res., 2013, 6(3), 411-414.
[33]
Lau, W.C.; Welch, T.D.; Shields, T.; Rubenfire, M.; Tantry, U.S.; Gurbel, P.A. The effect of St John’s Wort on the pharmacodynamic response of clopidogrel in hyporesponsive volunteers and patients: increased platelet inhibition by enhancement of CYP3A4 metabolic activity. J. Cardiovasc. Pharmacol., 2011, 57(1), 86-93.
[34]
Liu, A.C.; Zhao, L.X.; Lou, H.X. Curcumin alters the pharmacokinetics of warfarin and clopidogrel in Wistar rats but has no effect on anticoagulation or antiplatelet aggregation. Planta Med., 2013, 79(11), 971-977.
[35]
Yang, M.S.; Law, F.C.; Wong, R.N.; Mak, N.K.; Wei, X.Y. Interaction between oseltamivir and herbal medicines used for treating avian influenza. Hong Kong Med. J., 2012, 18(Suppl. 6), 34-36.
[36]
Guan, H.Y.; Li, P.F.; Wang, X.M.; Yue, J.J.; He, Y.; Luo, X.M.; Su, M.F.; Liao, S.G.; Shi, Y. Shengjiang Xiexin decoction alters pharmacokinetics of irinotecan by regulating metabolic enzymes and transporters: A multi-target therapy for alleviating the gas- trointestinal toxicity. Front. Pharmacol., 2017, 8, 769.
[37]
Rodriguez-Mateos, A.; Vauzour, D.; Krueger, C.G.; Shanmuga-nayagam, D.; Reed, J.; Calani, L.; Mena, P.; Del Rio, D.; Crozier, A. Bioavailability, bioactivity and impact on health of dietary flavonoids and related compounds: An update. Arch. Toxicol., 2014, 88(10), 1803-1853.
[38]
Yu, K.; Chen, F.; Li, C. Absorption, disposition, and pharmacoki- netics of saponins from Chinese medicinal herbs: what do we know and what do we need to know more? Curr. Drug Metab., 2012, 13(5), 577-598.
[39]
Bachmann, K.A. Inhibition constants, inhibitor concentrations and the prediction of inhibitory drug drug interactions: pitfalls, progress and promise. Curr. Drug Metab., 2006, 7(1), 1-14.
[40]
Wang, X.; Wang, G.; Shi, J.; Aa, J.; Comas, R.; Liang, Y.; Zhu, H.J. CES1 genetic variation affects the activation of angiotensin- converting enzyme inhibitors. Pharmacogenomics J., 2016, 16(3), 220-230.


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Article Details

VOLUME: 20
ISSUE: 2
Year: 2019
Page: [130 - 137]
Pages: 8
DOI: 10.2174/1389200219666180330124050
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