Journal of Agricultural and Food Chemistry· 2026Q1
Species-Dependent Citrus–Simvastatin Interaction Profiles in an Acute Rat Model: Integrating Drug Disposition, Hepatic Redox, and Complementary Computational Analysis
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- Q1SCImago
- 2026year
Short summary
Citrus depressa Hayata peel extract, rich in polymethoxyflavones, raised hepatic GSH/GSSG ratio by 227% in rats, uncoupling drug disposition from redox response, unlike grapefruit which primarily disrupted CYP3A and transporter pathways.
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Key points
- Citrus depressa Hayata extract increased hepatic GSH/GSSG ratio by 227% in rats, indicating a distinct redox response.
- Grapefruit extract raised plasma simvastatin acid by 506% by disrupting CYP3A and transporter pathways.
- Drug disposition and hepatic redox response are separable interaction axes for citrus-statin effects.
- Grapefruit cannot represent the interaction profiles of the entire citrus genus.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Citrus species differ widely in flavonoid chemistry, yet grapefruit has come to represent the genus in citrus–statin interactions. To test whether this translates into species-dependent interaction profiles, six flavonoid-profiled citrus peel extracts (Citrus limon, C. depressa Hayata, C. maxima, C. × paradisi, C. × sinensis, and C. reticulata) were compared in a standardized acute rat model spanning drug disposition, CYP3A and transporter systems, hepatic redox status, and in silico analysis. The naringin-dominated C. × paradisi produced the most coordinated disruption of CYP3A and transporter pathways, raising plasma simvastatin acid at 1 h by 506% versus the simvastatin-only group, together with the least favorable redox profile. The polymethoxyflavone-rich C. depressa Hayata perturbed disposition mildly yet raised the hepatic GSH/GSSG ratio by 227%. Hepatic active-metabolite accumulation was therefore uncoupled from redox outcome, indicating that disposition and redox response are separable axes and that grapefruit cannot represent the citrus genus.
The authors' abstract, as published at the source. Journal of Agricultural and Food Chemistry, 2026 · DOI ↗
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