Hericioic Acids A–G and Hericiofuranoic Acid; Neurotrophic Agents from Cultures of the European Mushroom Hericium flagellum

[Image: see text] Neurodegenerative diseases are currently posing huge social, economic, and healthcare burdens among the aged populations worldwide with few and only palliative treatment alternatives available. Natural products continue to be a source of a vast array of potent neurotrophic molecules that could be considered as drug design starting points. The present study reports eight new isoindolinone and benzofuranone derivatives, for which we propose the trivial names, hericioic acids A–G (1–7) and hericiofuranoic acid (8), which were isolated from a solid culture (using rice as substrate) of the rare European edible mushroom Hericium flagellum. The chemical structures of these compounds were determined based on extensive 1D and 2D NMR spectroscopy along with HRESIMS analyses. The isolated compounds were assessed for their neurotrophic activity in rat pheochromocytoma cells (PC-12) to promote neurite outgrowth on 5 ng NGF supplementation; all the compounds increased neurite outgrowths, with compounds 3, 4, and 8 exhibiting the strongest effects.