Lentinula edodes (Shiitake) extract as a vitamin D receptor activator to enhance skin adaptogenic responses

Lentinula edodes (Shiitake) has been traditionally used in East Asian medicine for its immunomodulatory and skin-health benefits. Among its bioactive constituents, ergosterol— a provitamin D₂ precursor— plays an important role in maintaining skin homeostasis. In this study, we investigated the ability of an oil-soluble extract from Lentinula edodes (SMosE) to modulate vitamin D receptor (VDR)–dependent transcription and influence key biological processes involved in skin barrier integrity, hydration, wound repair, and sebum regulation, supporting its relevance for dermatological applications. SMosE was obtained through lipophilic extraction and standardized for ergosterol content (302.9 ± 74.7 mg/kg). Its activity was first evaluated in human keratinocytes and dermal fibroblasts, where SMosE 0.06% w/v significantly increased VDR-dependent transcription, promoted wound closure and repair, and modulated the expression of markers associated with epidermal differentiation, barrier function, and sebaceous activity. These molecular effects were further supported by ex vivo human skin explant experiments, which showed significant increases in both cytokeratin 10 and claudin-1 levels, consistent with enhanced epidermal maturation and improved tight junction integrity. The functional relevance of these findings was subsequently assessed in a randomized, double-blind, placebo-controlled pilot clinical trial involving 39 adults with oily and acne-prone skin. After 28 days of topical application, SMosE 0.06% w/v produced greater improvements than placebo in transepidermal water loss, skin hydration, sebum levels, and pore appearance. Overall, this integrated preclinical and clinical investigation suggests that a Lentinula edodes –derived extract can modulate vitamin D–related pathways in vitro and ex vivo and may translate these activities into measurable improvements in skin barrier function, hydration, and superficial lipid regulation in vivo. SMosE thus emerges as a novel ethnobotanical strategy with strong potential as a functional ingredient in dermatology and cosmetic applications for skin repair and resilience.