Furan Acids from Nutmeg and Their Neuroprotective and Anti-neuroinflammatory Activities

Nutmeg (Myristica fragrans) has been traditionally valued for its culinary and medicinal properties. In our ongoing efforts to discover pharmacologically active compounds from this spice, five new furan acids (2–6, jusahos B–F), one new neolignan (7, jusaho G), and six known compounds (1 and 8–12) were isolated from its nutmegs. The chemical structures of the compounds were elucidated using NMR spectroscopy and HRESIMS. Among them, compound 3 (jusaho C) demonstrated promising antineuroinflammatory and neuroprotective effects in BV2 and HT22 cells by modulating the MAPK/NF-κB signaling pathway, which was explored through network pharmacology, molecular docking, and experimental verification. Compound 3 also showed the improvement of locomotor activity in Caenorhabditis elegans model infected with Pseudomonas aeruginosa. These findings expand the phytochemical profile of M. fragrans, where only one furan acid was previously reported, and highlight nutmeg-derived compounds, particularly jusaho C, as potential functional food ingredients or nutraceuticals for managing neuroinflammatory conditions.