Chemical Constituents from Hericium erinaceus Promote Neuronal Survival and Potentiate Neurite Outgrowth via the TrkA/Erk1/2 Pathway

Abstract

Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new dihydropyridine compound (6) and one new natural product (2) together with five known compounds (1,3–5,7) were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS. The cell-based screening for bioactivity showed that 4-chloro-3,5-dimethoxybenzoic methyl ester (1) and a cyathane diterpenoid, erincine A (3), not only potentiated NGF-induced neurite outgrowth but also protected neuronally-differentiated cells against deprivation of NGF in PC12 pheochromocytoma cells. Additionally, compound 3 induced neuritogenesis in primary rat cortex neurons. Furthermore, our results revealed that TrkA-mediated and Erk1/2-dependant pathways could be involved in 1 and 3-promoted NGF-induced neurite outgrowth in PC12 cells.

Two New Cyathane Diterpenoids from Mycelial Cultures of the Medicinal Mushroom Hericium erinaceus and the Rare Species, Hericium flagellum

“…Immortalized PC12 cells derived from rat adrenal medullary tumor (pheochromocytoma) cells and that are widely employed as an in vitro model for neuronal differentiation and neurite outgrowth studies were used. PC12 cells require NGF to differentiate, upon which they stop proliferating, extend neurites, and become electrically excitable [ 13 ]. A direct neurotrophic effect of the test compounds was analyzed by incubating PC12 cells in the highest non-toxic concentration of each compound in serum-free medium.…”

“…Since PC12 cells do not produce NGF themselves [ 13 ], we used human 1321N1 astrocytoma cells to test for the induction of cyathane-induced NGF secretion. As a negative control, ethanol was used according to the final concentration of the dissolved compounds.…”

Polyoxygenated cyathane diterpenoids from the mushroom Cyathus africanus, and their neurotrophic and anti-neuroinflammatory activities

“…Although generally inedible, Cyathus species are well known as prolific producers of bioactive cyathane diterpenoids. We have been actively searching for novel bioactive compounds from basidiomycete fungi 13 – 17 . To gain access to this potential reservoir of bioactive compounds, the cryptic biosynthetic pathways have to be induced.…”

Potential Antidepressant Effects of Scutellaria baicalensis, Hericium erinaceus and Rhodiola rosea

“…In detail, H. erinaceus bioactive compounds, especially erinacines and hericones, possesses strong nerve growth factor (NGF)-stimulating properties, showing remarkable neurite outgrowth activities in various cell lines and in dissociated cells of brain, spinal cord, and retina [40,[97][98][99][100][101][102][103][104][105][106][107][108]. In detail, H. erinaceus enhances NGF-mediated neurite outgrowth via activation of the Trk/MEK/ERK and PI3K-Akt signalling pathways [105,106]. Recently, two novel H. erinaceus cyathane diterpenoid derivatives were shown to promote BDNF expression in vitro, suggesting a common, yet unknown, upstream target for both NGF and BDNF induction [109].…”