Metabolites from the mushroom Ganoderma lingzhi as stimulators of neural stem cell proliferation

Ganoderma lingzhi is a valuable, edible and medicinal fungus that has been widely used for the prevention and treatment of a broad range of diseases. In this study, spirolingzhines A-D, four meroterpenoids with a spiro[benzofuran-2,10-cyclopentane] motif, lingzhines A-F, six meroterpenoids with diverse ring systems, along with two known compounds were isolated from the fruiting bodies of this fungus. The structures and stereochemistry of these substances were determined by using spectroscopic, X-ray crystallographic and computational methods. Chiral HPLC was used to separate (-)- and (+)-antipodes of seven of ten meroterpenoids, which were isolated from the fungus as racemic mixtures. Several of the metabolites were found to promote proliferation of neural stem cells (NSCs) and, as such, they constitute a class of NSC stimulators. The most potent member of this series, (-)-spirolingzhine A, was shown to affect NSC cell cycle progression using the 5-bromo-2-deoxyuridine (BrdU) incorporation assay.