Lee, Jin Woo Park, No-June Jung, Yujung Durai, Prasannavenkatesh Kim, Yong Kee Park, Keunwan Kim, Su-Nam 2026-03-25T05:30:24Z 2026-03-25T05:30:24Z 2026-03-24 2026-03 1226-8453 https://pubs.kist.re.kr/handle/201004/154455 Background The skin serves as a critical barrier that maintains physiological homeostasis while protecting the body from environmental insults. Glucocorticoids (GCs) are effective anti-inflammatory agents, but prolonged use can compromise skin barrier integrity. Mineralocorticoid receptors (MRs) play a key role in GC-induced skin barrier dysfunction, although cross-talk with glucocorticoid receptors (GRs). This study investigates the potential of Korean Red Ginseng (KRG) and its active component, 20(R)-ginsenoside Rg3 (Rg3(R)), in modulating MR-associated signaling and attenuate GC-induced skin barrier impairment. Methods MR transcriptional activity was assessed using luciferase reporter assays. Expression of SIRT1 and filaggrin, key markers of skin barrier function, was evaluated by quantitative PCR and Western blotting. MR knockdown with siRNA was performed to confirm its regulatory role. Molecular docking simulations predicted potential interactions between Rg3(R) and the MR ligand-binding domain. Results GC treatment enhanced MR activation, reducing SIRT1 and filaggrin levels and compromising barrier integrity. KRG, particularly Rg3(R), attenuated GC-induced MR transactivation and nuclear localization, restoring SIRT1 and filaggrin expression and preserving keratinocyte differentiation. MR knockdown corroborated the protective effect of MR-associated pathway modulation. Molecular docking suggested a plausible interaction between Rg3(R) and the MR through direct binding. Conclusion This study elucidates the pivotal role of MR in mediating GC-induced skin barrier dysfunction and identifies Rg3(R) from KRG as a promising therapeutic candidate for restoring skin barrier integrity. The findings provide a mechanistic basis for targeting MR signaling in the development of novel interventions for GC-associated skin disorders. English 고려인삼학회 Korean Red Ginseng attenuates glucocorticoid-induced skin barrier dysfunction via mineralocorticoid receptor modulation Article 10.1016/j.jgr.2026.100980 1 Journal of Ginseng Research, v.50, no.2 Journal of Ginseng Research 50 2 Y scie scopus kci ART003312677 001707910900001 2-s2.0-105028180992 Plant Sciences Chemistry, Medicinal Integrative & Complementary Medicine Plant Sciences Pharmacology & Pharmacy Integrative & Complementary Medicine Article MAMMALIAN SIRTUINS EXPRESSION GINSENOSIDES CELLS RG3 DIFFERENTIATION PHARMACOLOGY MECHANISMS PHYSIOLOGY REVERSE Panax ginseng 20(R)-Ginsenoside Rg3 Skin barrier Filaggrin Mineralocorticoid receptor