Potential inhibition of major human cytochrome P450 isoenzymes by selected tropical medicinal herbs—Implication for herb–drug interactions

Showande, Segun Johnson; Fakeye, Titilayo O.; Kajula, Marena; Hokkanen, Juho; Tolonen, Ari

doi:10.1002/fsn3.789

Cited by 38 publications

(21 citation statements)

References 60 publications

(103 reference statements)

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“…Mangifera indica extract inhibited CYP1A2, 2A6, 2C9, 2D6 and 3A4 in a concentration-dependent manner [28]. In addition, M. indica and Alstonia boonei, significantly inhibited CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 and 3A4 [29] which are CYP enzymes that are largely responsible for the metabolism of several drugs in humans. Furthermore, mild inhibition of p-glycoprotein, a major class of transport proteins for xenobiotics, has also been reported with mangiferin (chemical constituent of M. indica) and the ethanol extract of Azadirachta indica [28,30].…”

Section: Discussionmentioning

confidence: 95%

Influence of MAMA decoction, an Herbal Antimalarial, on the Pharmacokinetics of Amodiaquine in Mice

Adepiti

Adeagbo

Adehin

et al. 2019

Eur J Drug Metab Pharmacokinet

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Background and Objective MAMA decoction (MD) is an antimalarial product prepared from the leaves of Mangifera indica L. (Anacardiaceae), Alstonia boonei De Wild (Apocynaceae), Morinda lucida Benth (Rubiaceae) and Azadirachta indica A. Juss (Meliaceae). A previous report showed that MD enhanced the efficacy of amodiaquine (AQ) in malaria-infected mice, thus suggesting a herb-drug interaction. The present study hence evaluated the effect of MD on the disposition of AQ in mice with a view to investigating a possible pharmacokinetic interaction. Methods In a 3-period study design, three groups of mice (n = 72) were administered oral doses of AQ (10 mg/kg/day) alone, concurrently with MD (120 mg/kg/day), and in the 3rd period, mice were given AQ after a 3-day pre-treatment with MD. Blood samples were collected between 0 and 96 h for quantification of AQ and its major metabolite, desethylamodiaquine, by a validated high-performance liquid chromatography method. Results Maximum concentrations of AQ increased by 12% with the concurrent dosing of MD and by 85% in the group of mice pre-treated with MD. The exposure and half-life of desethylamodiaquine increased by approximately 11% and 21%, respectively, with concurrent administration. Corresponding increases of approximately 20% and 33% of desethylamodiaquine were also observed in mice pre-treated with MD. Conclusion MD influenced the pharmacokinetics of AQ and desethylamodiaquine, its major metabolite. The increase in the half-life and systemic exposure of AQ following its co-administration with MD may provide a basis for the enhanced pharmacological effect of the combination in an earlier study in Plasmodium-infected mice.

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Section: Discussionmentioning

confidence: 95%

Influence of MAMA decoction, an Herbal Antimalarial, on the Pharmacokinetics of Amodiaquine in Mice

Adepiti

Adeagbo

Adehin

et al. 2019

Eur J Drug Metab Pharmacokinet

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“…Herbs may be used singly or in combination in the treatment of diseases 22 . It is very important to understand how drug exposure alters molecular mechanisms underlying many complex drug interactions.…”

Section: Determinants Of Pkmentioning

confidence: 99%

Current trends in drug metabolism and pharmacokinetics

Meng

Yang

et al. 2019

Acta Pharmaceutica Sinica B

190

124

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Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug–drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice.

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“…In this sense, the overall opinion is that the concomitantly administered drugs that may modulate these CYP isoenzymes activities will lead to clinically significant drug–drug interactions. Such interactions may result in serious adverse drug reactions, especially regarding drugs with short therapeutic windows such as carbamazepine, theophylline, digoxin warfarin, and phenytoin [49].…”

Section: Toxicokinetics and Pharmacodynamicsmentioning

confidence: 99%

Mitragyna speciosa: Clinical, Toxicological Aspects and Analysis in Biological and Non-Biological Samples

et al. 2019

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The abuse of psychotropic substances is a well-known phenomenon, and many of them are usually associated with ancestral traditions and home remedies. This is the case of Mitragyna speciosa (kratom), a tropical tree used to improve work performance and to withstand great heat. According to several published studies, the main reasons for kratom consumption involve improving sexual performance and endurance, but also social and recreational uses for the feeling of happiness and euphoria; it is also used for medical purposes as a pain reliever, and in the treatment of diarrhea, fever, diabetes, and hypertension. However, this plant has gained more popularity amongst young people over the last years. Since it is available on the internet for purchase, its use is now widely as a drug of abuse, namely as a new psychoactive substance, being a cheaper alternative to opioids that does not require medical prescription in most countries. According to internet surveys by the European Monitoring Centre for Drugs and Drug Addiction in 2008 and 2011, kratom was one of the most widely supplied new psychoactive substances. The composition of kratom is complex; in fact, more than 40 different alkaloids have been identified in Mitragyna speciosa so far, the major constituent being mitragynine, which is exclusive to this plant. Besides mitragynine, alkaloids such as corynantheidine and 7-hydroxamitragynine also present pharmacological effects, a feature that may be attributed to the remaining constituents as well. The main goal of this review is not only to understand the origin, chemistry, consumption, and analytical methodologies for analysis and mechanism of action, but also the use of secondary metabolites of kratom as therapeutic drugs and the assessment of potential risks associated with its consumption, in order to aid health professionals, toxicologists, and police authorities in cases where this plant is present.

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Potential inhibition of major human cytochrome P450 isoenzymes by selected tropical medicinal herbs—Implication for herb–drug interactions

Cited by 38 publications

References 60 publications

Influence of MAMA decoction, an Herbal Antimalarial, on the Pharmacokinetics of Amodiaquine in Mice

Influence of MAMA decoction, an Herbal Antimalarial, on the Pharmacokinetics of Amodiaquine in Mice

Current trends in drug metabolism and pharmacokinetics

Mitragyna speciosa: Clinical, Toxicological Aspects and Analysis in Biological and Non-Biological Samples

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