Anti‐Photoaging Effects and Potential Molecular Mechanisms of Ergothioneine‐Derived‐ <i>Ganoderma lucidum</i> on UVB‐Irradiated Skin

ABSTRACT The increasing incidence of skin photoaging associated with enhanced ultraviolet (UV) exposure highlights the need for effective preventive and therapeutic interventions. This study aimed to determine the ergothioneine (EGT) content in different anatomical parts of Ganoderma lucidum and to evaluate its anti‐photoaging effects using HaCaT cells and an ultraviolet B (UVB)‐induced nude mouse model. EGT was detected exclusively in G. lucidum spore powder and significantly enhanced cell viability, hydroxyproline (HYP) content, and pro‐collagen I α1 levels in HaCaT cells following UVB irradiation. EGT markedly suppressed both the secretion and gene expression of pro‐inflammatory cytokines (IL‐6, TNF‐α, and IL‐1β), while upregulating the expression of collagen I and transforming growth factor‐β1. In addition, EGT‐derived‐ G. lucidum inhibited matrix metalloproteinases (MMP‐1, MMP‐3, and MMP‐9) and promoted the secretion of tissue inhibitors of metalloproteinases‐1 (TIMP‐1). Histological evaluation and gut microbiota analyses further demonstrated that EGT‐derived‐ G. lucidum alleviated UVB‐induced skin damage and partially restored microbial homeostasis. These findings indicate that G. lucidum ‐derived EGT exhibits significant anti‐photoaging activity and may represent a promising functional ingredient for anti‐photoaging applications.