Neurotrophic and Immunomodulatory Lanostane Triterpenoids from Wood-Inhabiting Basidiomycota

Neurotrophins such as nerve growth factor (ngf) and brain-derived neurotrophic factor
(bdnf) play important roles in the central nervous system. They are potential therapeutic drugs for
the treatment of neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s
disease. In this study, we investigated the neurotrophic properties of triterpenes isolated from
fruiting bodies of Laetiporus sulphureus and a mycelial culture of Antrodia sp. MUCL 56049. The
structures of the isolated compounds were elucidated based on nuclear magnetic resonance (NMR)
spectroscopy in combination with high-resolution electrospray mass spectrometry (HR-ESIMS).
The secondary metabolites were tested for neurotrophin (ngf and bdnf) expression levels on human
astrocytoma 1321N1 cells. Neurite outgrowth activity using rat pheochromocytoma (PC-12) cells
was also determined. Twelve triterpenoids were isolated, of which several potently stimulated the
expression of neurotrophic factors, namely, ngf (sulphurenic acid, 15α-dehydroxytrametenolic acid,
fomefficinic acid D, and 16α-hydroxyeburicoic acid) and bdnf (sulphurenic acid and 15α-
dehydroxytrametenolic acid), respectively. The triterpenes also potentiated ngf-induced neurite
outgrowth in PC-12 cells. This is, to the best of our knowledge, the first report on the compound
class of lanostanes in direct relation to bdnf and ngf enhancement. These compounds are
widespread in medicinal mushrooms; hence, they appear promising as a starting point for the
development of drugs and mycopharmaceuticals to combat neurodegenerative diseases.
Interestingly, they do not show any pronounced cytotoxicity and may, therefore, be better suited
for therapy than many other neurotrophic compounds that were previously reported.