Ergothioneine Modulates Inflammatory Signaling in LPS-Stimulated RAW 264.7 Macrophages

Ergothioneine (EGT), a naturally occurring antioxidant abundant in Hericium erinaceus, has been implicated in inflammation-related disorders, including inflammatory bowel disease (IBD). A validated HPLC-DAD method was developed for EGT quantification in H. erinaceus, demonstrating satisfactory specificity, linearity, precision, and accuracy. Network pharmacology analysis identified shared targets between EGT-associated proteins and IBD-related genes, with HSP90AA1 emerging as a key candidate. Molecular docking revealed stable binding of EGT within the HSP90AA1 active site. In lipopolysaccharide-stimulated RAW 264.7 macrophages, EGT significantly reduced the expression of pro-inflammatory mediators, including inducible nitric oxide synthase and cyclooxygenase-2, while modulating PPARγ expression. These findings provide integrated chemical and mechanistic evidence supporting EGT as a bioactive constituent of H. erinaceus with potential relevance for modulating intestinal inflammation. However, further studies are required to validate its therapeutic relevance in disease-specific models.