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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number11920
JournalScientific reports
Volume11
Issue number1
DOIs
Publication statusPublished - 2021 Dec

Bibliographical note

Funding Information:
This work was supported by AMOREPACIFIC and the National Research Foundation of Korea grant funded by the Korean government (NRF-2018R1A2B2005002).

Publisher Copyright:
© 2021, The Author(s).

All Science Journal Classification (ASJC) codes

  • General

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