Cytochrome P450 3A4 Suppression by Epimedium Can enhance Anti-Inflammatory Effect of Corticosteroid

Author Type(s)

Faculty

Document Type

Abstract

Publication Date

2023

DOI

10.1016/j.jbc.2023.103332

Journal Title

Journal of Biological Chemistry

Department

Pathology, Microbiology and Immunology

Abstract

Corticosteroids (CS) are the most widely used anti-inflammatory medication and the first line of therapy for a variety of chronic inflammatory autoimmune and allergic disorders. While extremely efficacious, prolonged use of CS is problematic due to the high risk of serious adverse effects. Cytochrome P450 (CYP) 3A4 is a major drug metabolizing enzyme for corticosteroids (CS). Epimedium has been used for asthma and variety of inflammatory conditions with or without CS. It is unknown whether epimedium has an effect on CYP 3A4 and how it interacts with CS. In this study we sought to determine the effects of epimedium on CYP3A4 and whether it affects the anti-inflammatory function of CS. We used RT-PCR and western blotting to determine the effect of epimedium on CYP3A4 mRNA and protein expression respectively in a human hepatocyte carcinoma (HepG2) cell with or without epimedium, dexamethasone, rifampin, and ketoconazole. Epimedium inhibited the expression of CYP3A4 mRNA and further suppressed dexamethasone enhancement of CYP3A4 mRNA expression in HepG2 cells (p < 0.05). Epimedium inhibited the protein expression of CYP3A4 (p < 0.05). In this study we showed that epimedium has an inhibitory effect on CYP3A4, a corticosteroid drug metabolizing enzyme, which can affect the metabolism and bioavailability of corticosteroids, potentially enhancing its anti-inflammatory effect. The result of this study warrants further in vitro and clinical investigation to fully understand the potential mechanisms and by which epimedium mediates it effect. Epimedium might be a potential combination therapeutic option that can enhance anti-inflammatory effect of corticosteroids ensuring appropriate dosing for long-term corticosteroid use.

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