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Therapeutic Agents with AHR Inhibiting and NRF2 Activating Activity for Managing Chloracne
Masutaka Furue1,2,3, Yoko Fuyuno4,5, Chikage Mitoma6,7
1Department of Dermatology, Kyushu University, Maidashi 3-1-1, Higashiku, Fukuoka 812-8582, Japan. furue@dermatol.med.kyushu-u.ac.jp.
Abstract:
Chloracne is the major skin symptom caused by dioxin intoxication. Dioxin activates the aryl hydrocarbon receptor (AHR)⁻cytochrome p450 1A1 (CYP1A1) system, generates oxidative stress, and induces hyperkeratinization of keratinocytes and sebocytes leading to chloracne. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a master switch that induces the expression of various antioxidative enzymes, such as heme oxygenase-1. Cinnamaldehyde is an antioxidant phytochemical that inhibits AHR⁻CYP1A1 signaling and activates the NRF2⁻antioxidative axis. The cinnamaldehyde-containing Kampo herbal medicine Keishibukuryogan is capable of improving chloracne in Yusho patients who are highly contaminated with dioxin. Agents with dual functions in promoting AHR⁻CYP1A1 inhibition and NRF2 activation may be useful for managing dioxin-related health hazards.
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