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UHPLC-MS/MS standardized extract of Vernonia amygdalina leaf inhibits CYP2C9 and CYP3A4 activities in hepatic cells of control and streptozotocin-induced diabetic rats

  • Bassel Al. Sabbagh , Vijayaraj Kumar Palanirajan , Yik-Ling Chew , Jin Han Chin , Mariam Ahmad and Gabriel Akyirem Akowuah ORCID logo EMAIL logo
Published/Copyright: December 12, 2024
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Drug Metabolism and Personalized Therapy
From the journal Drug Metabolism and Personalized Therapy Volume 39 Issue 4

Abstract

Objectives

Vernonia amygdalina Del. is a perennial tropical shrub from Asteraceae. The fresh leaf of V. amygdalina is consumed as a vegetable due to its medicinal and nutritional properties. The present study focused on the quantification of bioactive compounds, luteolin-7-O-glucoside, luteolin-7-O-glucuronide, and 1,5-O-dicaffeoylquinic acid from aqueous leaf extract of V. amygdalina. The study also aims to investigate the effects of the aqueous leaf extract of V. amygdalina on cytochrome P450 2C9 (CYP2C9), and cytochrome P450 3A4 (CYP3A4) in hepatic cells of control and diabetic rats.

Methods

The quantification of the bioactive compounds was conducted using ultra-high-performance liquid chromatography multiple reactions monitoring tandem mass spectrometry (UHPLC-MS/MS-MRM) technique. The effect of the extract on CYP2C9 and CYP3A4 activities was determined using a fluorometric screening kit according to the manufacturer’s instructions.

Results

The three bioactive compounds were detected and quantified in the aqueous leaf extract. Results showed that the content of luteolin-7-O-glucuronide (47 μg/mg) was the highest followed by luteolin-7-O-glucoside (3.5 μg/mg) and 1,5-O-dicaffeoylquinic acid (1.07 μg/mg). The extract showed an inhibitory effect on CYP3A4 and CYP2C9 enzyme activities in control and diabetic rats.

Conclusions

The UHPLC-MS/MS-MRM method is sensitive and reliable for the quality control of V. amygdalina leaf extract. The inhibitory effect of the extract suggests that concomitant use of V. amygdalina leaf preparations with conventional drugs metabolized and eliminated from the body by CYP3A4 and CYP2C9 enzymes may lead to possible interaction.

Keywords: bioactive compounds; multiple reaction monitoring; tandem mass spectrometry; cytochrome P450 inhibition; Vernonia amygdalina
Corresponding author: Dr. Gabriel Akyirem Akowuah, School of Pharmacy, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia, E-mail:

  1. Research ethics: The experimental procedures of the animal studies were approved by the Animal Ethics Committee of Universiti Kebangsaan Malaysia Animal Ethics Committee (UKMAEC/1132).

  2. Informed consent: Not applicable.

  3. Author contributions: All authors contributed to the study, accepted responsibility for the entire content of this manuscript, and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: None declared.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: The research work was financially supported by the UCSI University Research Grant Scheme (Proj-In-FPS-025) awarded by the Centre of Excellence for Research, Value Innovation and Entrepreneurship (CERVIE), UCSI University.

  7. Data availability: Not applicable.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/dmpt-2024-0005).

Received: 2024-02-02
Accepted: 2024-10-07
Published Online: 2024-12-12

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/dmpt-2024-0005
Keywords for this article
bioactive compounds; multiple reaction monitoring; tandem mass spectrometry; cytochrome P450 inhibition; Vernonia amygdalina

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. ‘Pharmacogenetics, health and ethnicity in Latin American populations’ call for the “Dr José María Cantú Award 2024”
  4. Reviews
  5. Current developments and advancements of 3-dimensional printing in personalized medication and drug screening
  6. Status of the implementation of pharmacogenetics in clinical practice in Spain: from regional to national initiatives
  7. Minireview
  8. CYP2C19 genotype-phenotype correlation: current insights and unanswered questions
  9. Original Articles
  10. Pediatric pharmacogenetics: profiling CYP2C8 polymorphisms at King Abdulaziz University Dental Clinic
  11. Optimizing tacrolimus therapeutic drug monitoring in Tunisian kidney transplant recipients: exploring the variability in bioavailability and the correlation between pharmacokinetic parameters
  12. Efficacy and safety of a polyherbal formulation in the management of Escherichia coli urinary tract infection
  13. UHPLC-MS/MS standardized extract of Vernonia amygdalina leaf inhibits CYP2C9 and CYP3A4 activities in hepatic cells of control and streptozotocin-induced diabetic rats
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