A novel mineralocorticoid receptor antagonist, 7,3',4'-trihydroxyisoflavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids

Abstract Excess glucocorticoids (GCs) with either endogenous or exogenous origins deteriorate skin barrier function. GCs bind to mineralocorticoid and GC receptors (MRs and GRs) in normal human epidermal keratinocytes (NHEKs). Inappropriate MR activation by GCs mediates various GC-induced cutaneous...

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Autores principales:	Hanil Lee, Eun-Jeong Choi, Eun Jung Kim, Eui Dong Son, Hyoung-June Kim, Won-Seok Park, Young-Gyu Kang, Kyong-Oh Shin, Kyungho Park, Jin-Chul Kim, Su-Nam Kim, Eung Ho Choi
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Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/13816f2d1f114bb5aea0abb848a7f618
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spelling	oai:doaj.org-article:13816f2d1f114bb5aea0abb848a7f6182021-12-02T14:58:20ZA novel mineralocorticoid receptor antagonist, 7,3',4'-trihydroxyisoflavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids10.1038/s41598-021-91450-62045-2322https://doaj.org/article/13816f2d1f114bb5aea0abb848a7f6182021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91450-6https://doaj.org/toc/2045-2322Abstract Excess glucocorticoids (GCs) with either endogenous or exogenous origins deteriorate skin barrier function. GCs bind to mineralocorticoid and GC receptors (MRs and GRs) in normal human epidermal keratinocytes (NHEKs). Inappropriate MR activation by GCs mediates various GC-induced cutaneous adverse events. We examined whether MR antagonists can ameliorate GC-mediated skin barrier dysfunction in NHEKs, reconstructed human epidermis (RHE), and subjects under psychological stress (PS). In a preliminary clinical investigation, topical MR antagonists improved skin barrier function in topical GC-treated subjects. In NHEKs, cortisol induced nuclear translocation of GR and MR, and GR and MR antagonists inhibited cortisol-induced reductions of keratinocyte differentiation. We identified 7,3’,4’-trihydroxyisoflavone (7,3’,4’-THIF) as a novel compound that inhibits MR transcriptional activity by screening 30 cosmetic compounds. 7,3’,4’-THIF ameliorated the cortisol effect which decreases keratinocyte differentiation in NHEKs and RHE. In a clinical study on PS subjects, 7,3',4'-THIF (0.1%)-containing cream improved skin barrier function, including skin surface pH, barrier recovery rate, and stratum corneum lipids. In conclusion, skin barrier dysfunction owing to excess GC is mediated by MR and GR; thus, it could be prevented by treatment with MR antagonists. Therefore, topical MR antagonists are a promising therapeutic option for skin barrier dysfunction after topical GC treatment or PS.Hanil LeeEun-Jeong ChoiEun Jung KimEui Dong SonHyoung-June KimWon-Seok ParkYoung-Gyu KangKyong-Oh ShinKyungho ParkJin-Chul KimSu-Nam KimEung Ho ChoiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hanil Lee Eun-Jeong Choi Eun Jung Kim Eui Dong Son Hyoung-June Kim Won-Seok Park Young-Gyu Kang Kyong-Oh Shin Kyungho Park Jin-Chul Kim Su-Nam Kim Eung Ho Choi A novel mineralocorticoid receptor antagonist, 7,3',4'-trihydroxyisoflavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids
description	Abstract Excess glucocorticoids (GCs) with either endogenous or exogenous origins deteriorate skin barrier function. GCs bind to mineralocorticoid and GC receptors (MRs and GRs) in normal human epidermal keratinocytes (NHEKs). Inappropriate MR activation by GCs mediates various GC-induced cutaneous adverse events. We examined whether MR antagonists can ameliorate GC-mediated skin barrier dysfunction in NHEKs, reconstructed human epidermis (RHE), and subjects under psychological stress (PS). In a preliminary clinical investigation, topical MR antagonists improved skin barrier function in topical GC-treated subjects. In NHEKs, cortisol induced nuclear translocation of GR and MR, and GR and MR antagonists inhibited cortisol-induced reductions of keratinocyte differentiation. We identified 7,3’,4’-trihydroxyisoflavone (7,3’,4’-THIF) as a novel compound that inhibits MR transcriptional activity by screening 30 cosmetic compounds. 7,3’,4’-THIF ameliorated the cortisol effect which decreases keratinocyte differentiation in NHEKs and RHE. In a clinical study on PS subjects, 7,3',4'-THIF (0.1%)-containing cream improved skin barrier function, including skin surface pH, barrier recovery rate, and stratum corneum lipids. In conclusion, skin barrier dysfunction owing to excess GC is mediated by MR and GR; thus, it could be prevented by treatment with MR antagonists. Therefore, topical MR antagonists are a promising therapeutic option for skin barrier dysfunction after topical GC treatment or PS.
format	article
author	Hanil Lee Eun-Jeong Choi Eun Jung Kim Eui Dong Son Hyoung-June Kim Won-Seok Park Young-Gyu Kang Kyong-Oh Shin Kyungho Park Jin-Chul Kim Su-Nam Kim Eung Ho Choi
author_facet	Hanil Lee Eun-Jeong Choi Eun Jung Kim Eui Dong Son Hyoung-June Kim Won-Seok Park Young-Gyu Kang Kyong-Oh Shin Kyungho Park Jin-Chul Kim Su-Nam Kim Eung Ho Choi
author_sort	Hanil Lee
title	A novel mineralocorticoid receptor antagonist, 7,3',4'-trihydroxyisoflavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids
title_short	A novel mineralocorticoid receptor antagonist, 7,3',4'-trihydroxyisoflavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids
title_full	A novel mineralocorticoid receptor antagonist, 7,3',4'-trihydroxyisoflavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids
title_fullStr	A novel mineralocorticoid receptor antagonist, 7,3',4'-trihydroxyisoflavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids
title_full_unstemmed	A novel mineralocorticoid receptor antagonist, 7,3',4'-trihydroxyisoflavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids
title_sort	novel mineralocorticoid receptor antagonist, 7,3',4'-trihydroxyisoflavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/13816f2d1f114bb5aea0abb848a7f618
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A novel mineralocorticoid receptor antagonist, 7,3',4'-trihydroxyisoflavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids

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