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

Nutmeg (<i>Myristica fragrans</i>) 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 (<b>2</b>-<b>6</b>, jusahos B-F), one new neolignan (<b>7</b>, jusaho G), and six known compounds (<b>1</b> and <b>8</b>-<b>12</b>) were isolated from its nutmegs. The chemical structures of the compounds were elucidated using NMR spectroscopy and HRESIMS. Among them, compound <b>3</b> (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 <b>3</b> also showed the improvement of locomotor activity in <i>Caenorhabditis elegans</i> model infected with <i>Pseudomonas aeruginosa</i>. These findings expand the phytochemical profile of <i>M. fragrans</i>, 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.