Trihydroxyisoflavone Improves Skin Barrier Function Impaired by E
www.nature.com/scientificreports OPEN A novel mineralocorticoid receptor antagonist, 7,3’,4’‑trihydroxyisofavone improves skin barrier function impaired by endogenous or exogenous glucocorticoids Hanil Lee1,5, Eun‑Jeong Choi2,5, Eun Jung Kim1, Eui Dong Son2, Hyoung‑June Kim2, Won‑Seok Park2, Young‑Gyu Kang2, Kyong‑Oh Shin3, Kyungho Park3, Jin‑Chul Kim4, Su‑Nam Kim4 & Eung Ho Choi1* 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 diferentiation. We identifed 7,3’,4’‑trihydroxyisofavone (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 efect which decreases keratinocyte diferentiation 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.
[Show full text]