Lucidenic Acid A-rich Antler-shaped Ganoderma lucidum Extract Enhances Skin Barrier and Suppresses Staphylococcus aureus Infection

This study was conducted to evaluate the skin barrier enhancing effects and the potential to alleviate Staphylococcus aureus–associated skin disorders of an antler-shaped Ganoderma lucidum extract (AGL-E) enriched in lucidenic acid A (LAA). HPLC analysis revealed that the LAA content of AGL-E was 1.29%, approximately 14-fold higher than that of a conventional G. lucidum extract (0.09%). In HaCaT cells, MTT assays showed that AGL-E exhibited no cytotoxicity at concentrations up to 100 μg/mL, while LAA was non-cytotoxic at concentrations up to 50 μg/mL. Analysis of mRNA expression of skin barrierrelated markers, including filaggrin (FLG), loricrin (LOR), and involucrin (IVL), demonstrated that AGL-E significantly upregulated FLG and LOR expression, suggesting its potential to enhance epidermal barrier formation through modulation of keratinocyte differentiation. In contrast, LAA significantly increased the expression of FLG and IVL, indicating its contribution to barrier-related functional enhancement. Furthermore, both AGL-E and LAA significantly suppressed S. aureus–induced secretion of pro-inflammatory cytokines, including IL-1β and TNF-α. In a S. aureus infection model labeled with CellTrace^TMFar-red, treatment with AGL-E or LAA markedly reduced S. aureus-associated infection levels in keratinocytes, confirming their infection-inhibitory effects. Collectively, these findings suggest that AGL-E exerts multifunctional protective effects in skin environments characterized by barrier disruption and microbe-associated inflammation by modulating barrier-related differentiation markers and suppressing S. aureus–induced inflammatory and infectious responses, with LAA suggested as a contributing bioactive constituent.