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Open AccessArticle

Baicalein Inhibits Benzo[a]pyrene-Induced Toxic Response by Downregulating Src Phosphorylation and by Upregulating NRF2-HMOX1 System

1
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
2
Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, Fukuoka 812-8582, Japan
3
Division of Skin Surface Sensing, Department of Dermatology, Faculty of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan
*
Author to whom correspondence should be addressed.
Antioxidants 2020, 9(6), 507; https://doi.org/10.3390/antiox9060507
Received: 1 June 2020 / Accepted: 8 June 2020 / Published: 9 June 2020
(This article belongs to the Special Issue Feature Papers in Antioxidants in 2020)
Benzo[a]pyrene (BaP), a major environmental pollutant, activates aryl hydrocarbon receptor (AHR), induces its cytoplasmic-to-nuclear translocation and upregulates the production of cytochrome P450 1A1 (CYP1A1), a xenobiotic metabolizing enzyme which metabolize BaP. The BaP-AHR-CYP1A1 axis generates reactive oxygen species (ROS) and induces proinflammatory cytokines. Although the anti-inflammatory phytochemical baicalein (BAI) is known to inhibit the BaP-AHR-mediated CYP1A1 expression, its subcellular signaling remains elusive. In this study, normal human epidermal keratinocytes and HaCaT keratinocytes were treated with BAI, BaP, or BAI + BaP, and assessed for the CYP1A1 expression, antioxidative pathways, ROS generation, and proinflammatory cytokine expressions. BAI and BAI-containing herbal medicine Wogon and Oren-gedoku-to could inhibit the BaP-induced CYP1A1 expression. In addition, BAI activated antioxidative system nuclear factor-erythroid 2-related factor-2 (NRF2) and heme oxygenase 1 (HMOX1), leading the reduction of BaP-induced ROS production. The BaP-induced IL1A and IL1B was also downregulated by BAI. BAI inhibited the phosphorylation of Src, a component of AHR cytoplasmic complex, which eventually interfered with the cytoplasmic-to-nuclear translocation of AHR. These results indicate that BAI and BAI-containing herbal drugs may be useful for inhibiting the toxic effects of BaP via dual AHR-CYP1A1-inhibiting and NRF2-HMOX1-activating activities. View Full-Text
Keywords: baicalein; benzo[a]pyrene; Src; aryl hydrocarbon receptor; nuclear factor-erythroid 2-related factor-2; reactive oxygen species; keratinocyte; Wogon; Oren-gedoku-to baicalein; benzo[a]pyrene; Src; aryl hydrocarbon receptor; nuclear factor-erythroid 2-related factor-2; reactive oxygen species; keratinocyte; Wogon; Oren-gedoku-to
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Tanaka, Y.; Ito, T.; Tsuji, G.; Furue, M. Baicalein Inhibits Benzo[a]pyrene-Induced Toxic Response by Downregulating Src Phosphorylation and by Upregulating NRF2-HMOX1 System. Antioxidants 2020, 9, 507.

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