Erinacine S from Hericium erinaceus mycelium promotes neuronal regeneration by inducing neurosteroids accumulation

Erinacines derived from Hericium erinaceus have been shown to possess various health benefits including neuro-protective effect against neurodegenerative diseases, yet the underlying mechanism remains unknown. Here we found that erinacine S enhances neurite outgrowth in a cell autonomous fashion. It promotes post-injury axon regeneration of PNS neurons and enhances regeneration on inhibitory substrates of CNS neurons. Using RNA-seq and bioinformatic analyses, erinacine S was found to cause the accumulation of neurosteroids in neurons. ELISA and neurosteroidogenesis inhibitor assays were performed to validate this effect. This research uncovers a previously unknown effect of erinacine S on raising the level of neurosteroids.