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Planta Med 2024; 90(10): 792-800
DOI: 10.1055/a-2360-4808
Biological and Pharmacological Activity
Original Papers

Evaluation of the Effects of Extracts Containing Valeriana officinalis and Piper methysticum on the Activities of Cytochrome P450 3A and P-Glycoprotein

Mariana de Lima Nascimento
1   Universidade Federal de São João del-Rei, Campus Centro-Oeste Dona Lindu, Chanadour, Divinópolis-MG, Brazil
,
Sara Batista do Nascimento
1   Universidade Federal de São João del-Rei, Campus Centro-Oeste Dona Lindu, Chanadour, Divinópolis-MG, Brazil
,
Ednalva de Souza Pereira Lima
1   Universidade Federal de São João del-Rei, Campus Centro-Oeste Dona Lindu, Chanadour, Divinópolis-MG, Brazil
,
Flávio Martins de Oliveira
1   Universidade Federal de São João del-Rei, Campus Centro-Oeste Dona Lindu, Chanadour, Divinópolis-MG, Brazil
,
Rafael Rocha dos Santos
2   Universidade Federal de Minas Gerais, Campus Pampulha, Belo Horizonte-MG, Brazil
,
Isabela da Costa Cesar 
2   Universidade Federal de Minas Gerais, Campus Pampulha, Belo Horizonte-MG, Brazil
,
Whocely Victor de Castro 
1   Universidade Federal de São João del-Rei, Campus Centro-Oeste Dona Lindu, Chanadour, Divinópolis-MG, Brazil
› Author AffiliationsSupported by: Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG)
Supported by: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) 001
Supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 444467/2023-8
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Abstract

This work investigated interactions ascribed to the administration of phytomedicines containing Valeriana officinalis and Piper methysticum with conventional drugs. The phytomedicines were characterized by HPLC and administered per os to male Wistar rats, either concomitantly or not with the CYP3A substrate midazolam. To distinguish between the presystemic or systemic effect, midazolam was given orally and intravenously. The effects on the P-gp substrate fexofenadine uptake by Caco-2 cells were examined. The valerenic acid content was 1.6 ± 0.1 mg per tablet, whereas kavain was 13.7 ± 0.3 mg/capsule. Valerian and kava-kava extracts increased the maximum plasma concentration (Cmax) of midazolam 2- and 4-fold compared to the control, respectively. The area under the plasma concentrations versus time curve (AUC(0-∞)) was enhanced from 994.3 ± 152.3 ng.h/mL (control) to 3041 ± 398 ng.h/mL (valerian) and 4139 ± 373 ng.h/mL (kava-kava). The half-life of midazolam was not affected. These changes were attributed to the inhibition of midazolam metabolism by the enteric CYP3A since the i. v. pharmacokinetic of midazolam remained unchanged. The kava-kava extract augmented the uptake of fexofenadine by 3.5-fold compared to the control. Although Valeriana increased the uptake of fexofenadine, it was not statistically significant to that of the control (12.5 ± 3.7 ng/mg protein vs. 5.4 ± 0.3 ng/mg protein, respectively). Therefore, phytomedicines containing V. officinalis or P. methysticum inhibited the intestinal metabolism of midazolam in rats. Conversely, the P-gp-mediated transport of fexofenadine was preferably affected by kava-kava.

Keywords

Valeriana officinalis - Caprifoliaceae - Piper methysticum - Piperaceae - cytochrome P450 - P-glycoprotein

Supporting Information

    A chromatogram and UV spectrum of the standard solution of valerenic acid and valerian tablets as well as a chromatogram of the standard solution of kavain and capsules of Piper methysticum are available as Supporting Information.

  • Supporting Information


Publication History

Received: 14 November 2023

Accepted after revision: 21 June 2024

Article published online:
16 July 2024

© 2024. Thieme. All rights reserved.

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