Effect of Berberine on in vitro metabolism of Sulfonylureas: a herb-drug interactions study

Singh, Amrinder ORCID logoORCID: https://orcid.org/0000-0003-3247-1168, Zhao, Kaicun, Bell, Celia M. ORCID logoORCID: https://orcid.org/0000-0002-3270-7081 and Shah, Ajit J. ORCID logoORCID: https://orcid.org/0000-0002-2350-6384 (2020) Effect of Berberine on in vitro metabolism of Sulfonylureas: a herb-drug interactions study. Rapid Communications in Mass Spectrometry, 34 (S4) , e8651. pp. 1-12. ISSN 0951-4198 [Article] (doi:10.1002/rcm.8651)

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Abstract

Rationale: Patients with type 2 diabetes may co-ingest herbal and prescription medicine to control their blood sugar levels. Competitive binding of drug and herb may mutually affect their metabolism. This can alter the level of drug and its kinetics in the body, potentially causing toxicities or loss of efficacy. Understanding how metabolism of sulfonylureas like glyburide and gliclazide can be affected by the presence of berberine and vice versa can provide valuable information on the possible risk of toxicities caused by co-ingestion of drugs.

Methods: Berberine and sulfonylureas (glyburide and gliclazide) were co-incubated with rat liver microsomes in the presence of NADPH regenerating system. The metabolites of berberine and sulfonylureas were analysed using liquid chromatography with high resolution mass spectrometry in the positive ion mode. The role of individual isozymes in the metabolism of berberine, glyburide and gliclazide was investigated by using specific inhibitors.

Results: In vitro metabolism of berberine lead to the formation of demethyleneberberine (B1a) and B1b through demethylenation. Berberrubine (B2a) and its isomer (B2b) was formed through demethylation. The isozymes CYP3A and CYP2D were found to be involved in the metabolism of berberine. In vitro metabolism of glyburide and gliclazide lead to the formation of hydroxylated metabolites. The isozymes CYP3A and CYP2C were found to be involved in the metabolism of glyburide. Gliclazide was metabolised by CYP2C. In vitro co-incubation of glyburide or gliclazide with berberine showed that each drugs metabolism was compromised as both share a common isozymes. A strong negative linear correlation of glyburide or gliclazide metabolites levels and the concentration of berberine confirmed the effect of berberine on the metabolism of sulfonylureas

Item Type: Article
Additional Information: Special Issue research article
Volume34, IssueS4 - Special Issue: Dai Games
Keywords (uncontrolled): Organic Chemistry, Analytical Chemistry, Spectroscopy
Research Areas: A. > School of Science and Technology
Item ID: 28109
Notes on copyright: This is the peer reviewed version of the following article: Singh, A, Zhao, K, Bell, C, Shah, AJ. Effect of Berberine on In Vitro Metabolism of Sulfonylureas: A herb‐drug interactions study. Rapid Commun Mass Spectrom. 2020; 34( S4):e8651, which has been published in final form at https://doi.org/10.1002/rcm.8651. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
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Depositing User: Ajit Shah
Date Deposited: 06 Nov 2019 12:58
Last Modified: 29 Nov 2022 18:17
URI: https://eprints.mdx.ac.uk/id/eprint/28109

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