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Updated: Aug 21, 2026
Preparation of Naringenin Solution for In Vivo Application
Published on: August 10, 2021
Suppression of CYP1A1 expression by naringenin in murine Hepa-1c1c7 cells
Ji Young Kim1, Eun Hee Han, Dong Weon Shin
1Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, Kwangju 501-759, Korea.
Abstract:
Naringenin, dietary flavonoid, is antioxidant constituents of many citrus fruits. In the present study, we investigated the effect of naringenin on 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible CYP1A1 gene expression in mouse hepatoma Hepa-1c1c7 cells. Naringenin alone did not affect CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity. In contrast, the TCDD-inducible EROD activities were markedly reduced upon concomitant treatment with TCDD and naringenin in a dose dependent manner. TCDD-induced CYP1A1 mRNA level was also markedly suppressed by naringenin. A transient transfection assay using dioxin-response element (DRE)-linked luciferase and electrophoretic mobility shift assay revealed that naringenin reduced transformation of the aryl hydrocarbons receptor(AhR) to a form capable of specifically binding to the DRE sequence in the promoter of the CYP1A1 gene. These results suggest the down regulation of the CYP1A1 gene expression by either naringenin in Hepa-1c1c7 cells might be antagonism of the DRE binding potential of nuclear AhR.
Insights
Naringenin, a citrus flavonoid, inhibits TCDD-induced CYP1A1 gene expression by blocking the aryl hydrocarbon receptor
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Naringenin is a dietary flavonoid found in citrus fruits with known antioxidant properties.
- CYP1A1 gene expression can be induced by environmental toxins like 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
- The aryl hydrocarbon receptor (AhR) is a key transcription factor regulating CYP1A1 expression.
Purpose of the Study:
- To investigate the effect of naringenin on TCDD-inducible CYP1A1 gene expression in mouse hepatoma cells.
- To elucidate the molecular mechanism underlying naringenin's potential modulation of AhR activity.
Main Methods:
- Hepa-1c1c7 mouse hepatoma cells were used for in vitro studies.
- CYP1A1-specific 7-ethoxyresorufin O-deethylase (EROD) activity assays were performed.
- mRNA levels of CYP1A1 were quantified.
- Transient transfection assays with DRE-luciferase reporter constructs were employed.
- Electrophoretic mobility shift assays (EMSA) were conducted to assess AhR-DNA binding.
Main Results:
- Naringenin alone did not affect basal CYP1A1 activity.
- Concomitant treatment with TCDD and naringenin dose-dependently reduced TCDD-induced EROD activity.
- Naringenin significantly suppressed TCDD-induced CYP1A1 mRNA levels.
- Naringenin inhibited the formation of a DNA-binding active AhR complex, reducing its ability to bind the dioxin-response element (DRE).
Conclusions:
- Naringenin antagonizes the transcriptional activity of the aryl hydrocarbon receptor (AhR).
- Naringenin down-regulates CYP1A1 gene expression by interfering with AhR binding to the DRE in the CYP1A1 promoter.
- These findings suggest naringenin may act as a dietary modulator of toxicant-induced gene expression.
