Cacao polyphenol extract suppresses transformation of an aryl hydrocarbon receptor in C57BL/6 mice
Rie Mukai1, Itsuko Fukuda, Shin Nishiumi
1Department of Agrobioscienec, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe, Hyogo 657-8501, Japan.
Abstract:
Dioxins enter the body through the diet and cause various toxicological effects through transformation of an aryl hydrocarbon receptor (AhR). Plant extracts and phytochemicals including flavonoids are reported to suppress this transformation. This paper investigates the suppression by a cacao polyphenol extract (CPE) of AhR transformation in vivo. The CPE was administered orally to C57BL/6 mice at 100 mg/kg of body weight, followed 1 h later by 3-methylcholanthrene (MC), an AhR agonist, injected intraperitoneally at 10 mg/kg of body weight. CPE suppressed the MC-induced transformation to the control level by inhibiting the formation of a heterodimer between AhR and an aryl hydrocarbon receptor nuclear translocator in the liver at 3 h postadministration. It also suppressed MC-induced cytochrome P4501A1 expression and NAD(P)H:quinone-oxidoreductase activity, whereas it increased glutathione S-transferase activity at 25 h. CPE constituents and their metabolites might contribute, at least in part, to the suppression of AhR transformation. The results indicate that the intake of CPE suppressed the toxicological effects of dioxins in the body.
Insights
Cacao polyphenol extract (CPE) effectively suppresses dioxin toxic effects by inhibiting aryl hydrocarbon receptor (AhR) transformation in mice. This dietary intervention shows promise for mitigating dioxin-induced toxicity.
Area of Science:
- Toxicology
- Pharmacology
- Biochemistry
Background:
- Dioxins pose health risks by activating the aryl hydrocarbon receptor (AhR).
- Plant-derived compounds, such as flavonoids, may counteract AhR activation.
- Cacao polyphenol extract (CPE) is investigated for its potential to inhibit AhR transformation.
Purpose of the Study:
- To evaluate the in vivo efficacy of CPE in suppressing AhR transformation induced by 3-methylcholanthrene (MC).
- To determine the impact of CPE on key molecular markers of AhR activation and detoxification pathways.
Main Methods:
- C57BL/6 mice were orally administered CPE (100 mg/kg) followed by intraperitoneal injection of MC (10 mg/kg).
- Liver tissue was analyzed at 3 and 25 hours post-administration to assess AhR transformation, protein expression, and enzyme activities.
Main Results:
- CPE significantly suppressed MC-induced AhR transformation by inhibiting AhR/ARNT heterodimer formation in the liver.
- CPE reduced MC-induced cytochrome P4501A1 expression and NAD(P)H:quinone-oxidoreductase activity.
- CPE increased glutathione S-transferase activity, indicating enhanced detoxification.
Conclusions:
- CPE administration effectively mitigates dioxin-induced toxicological effects in mice.
- The suppressive action of CPE is attributed to its constituents and their metabolites interfering with AhR pathway activation.
- Dietary intake of CPE presents a potential strategy for reducing the adverse health impacts of dioxin exposure.
