Assessment of cytochrome P450 inhibition and induction potential of lupeol and betulin in rat liver microsomes
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Madhav Seervi
Abstract
Background: Lupeol and betulin are triterpenoids that are majorly found in dietary substances. The aim of present study was to investigate the inhibition and induction potential of lupeol and betulin on cytochrome P450 (CYP)1A2, CYP2C11, CYP2D6 and CYP3A2 activities in rat liver microsomes.
Methods: The inhibition and induction studies were conducted using ethoxy resorufin-O-deethylase (CYP1A2), tolbutamide hydroxylase (CYP2C9), and midazolam hydroxylase (CYP3A4) activity assays. In vitro inhibition study was evaluated by incubating lupeol and betulin (1, 3, 10, 30 and 100 μM) with rat liver microsomes, and the metabolite formation was analyzed by high-performance liquid chromatography. The induction study was conducted by administering lupeol (20 mg/kg) and betulin (50 mg/kg) intraperitoneally for 14 days to rats followed by liver isolation and microsome preparation.
Results: The IC50 values in inhibition studies were found to be 59.42 μM (CYP1A2), >100 μM (CYP2C11, CYP2D6, CYP3A2) for lupeol, 52.24 μM (CYP1A2), and >100 μM (CYP2C9, CYP2D6, CYP3A2) for betulin. There was no significant modification observed in the CYP450 isoforms, indicating neither inhibition nor induction potential of lupeol and betulin.
Conclusions: Lupeol and betulin have very low propensity to interact with CYP enzyme, suggesting no CYP inhibitory and inducing potential in rat liver microsomes.
Acknowledgments
The authors acknowledge the University Grants Commission (grant/award no. F-63/2007, BSR) for their financial support and Dr. Krishna Iyer, Bombay College of Pharmacy, for his valuable suggestions in study designing.
Author contributions: MS conducted the present study, which included aspects such as laboratory work, interpretation of data, and manuscript writing. SL assisted in the experimental part of study. SB provided lupeol and betulin for the study. SS was involved in planning the study design and also corrected manuscript write-up. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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©2016 by De Gruyter
Articles in the same Issue
- Frontmatter
- In Memoriam Gérard Siest
- Reviews
- Interethnic variability of pharmacogenetic biomarkers in Mexican healthy volunteers: a report from the RIBEF (Ibero-American Network of Pharmacogenetics and Pharmacogenomics)
- Predictive biomarkers candidates for patients with metastatic colorectal cancer treated with bevacizumab-containing regimen
- Mini Reviews
- The integration and interpretation of pharmacogenomics – a comparative study between the United States of America and Europe: towards better health care
- Investigating the impact of missense mutations in hCES1 by in silico structure-based approaches
- Original Articles
- Lack of genomic diversity in the SLC47A1 gene within the indigenous Xhosa population
- Assessment of cytochrome P450 inhibition and induction potential of lupeol and betulin in rat liver microsomes
- Altered pharmacokinetics and pharmacodynamics of repaglinide by ritonavir in rats with healthy, diabetic and impaired hepatic function
Articles in the same Issue
- Frontmatter
- In Memoriam Gérard Siest
- Reviews
- Interethnic variability of pharmacogenetic biomarkers in Mexican healthy volunteers: a report from the RIBEF (Ibero-American Network of Pharmacogenetics and Pharmacogenomics)
- Predictive biomarkers candidates for patients with metastatic colorectal cancer treated with bevacizumab-containing regimen
- Mini Reviews
- The integration and interpretation of pharmacogenomics – a comparative study between the United States of America and Europe: towards better health care
- Investigating the impact of missense mutations in hCES1 by in silico structure-based approaches
- Original Articles
- Lack of genomic diversity in the SLC47A1 gene within the indigenous Xhosa population
- Assessment of cytochrome P450 inhibition and induction potential of lupeol and betulin in rat liver microsomes
- Altered pharmacokinetics and pharmacodynamics of repaglinide by ritonavir in rats with healthy, diabetic and impaired hepatic function
