Hericium erinaceus (Bull.: Fr) Pers. cultivated under tropical conditions: isolation of hericenones and demonstration of NGF-mediated neurite outgrowth in PC12 cells via MEK/ERK and PI3K-Akt signaling pathways

Abstract

Hericium erinaceus (Bull.: Fr.) Pers. is an edible and medicinal mushroom used traditionally to improve memory. In this study, we investigated the neuritogenic effects of hericenones isolated from H. erinaceus and the mechanisms of action involved. H. erinaceus was cultivated and the secondary metabolites were elucidated by high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR). The secondary metabolites were tested for neurite outgrowth activity (if any). Rat pheochromocytoma (PC12) cells were employed and the nerve growth factor (NGF) level was also determined. The signaling pathways involved in the mushroom-induced neuritogenesis were investigated using several pharmacological inhibitors. Hericenones B-E (1-4), erinacerin A (5) and isohericerin (6) were isolated from the basidiocarps of H. erinaceus. The hericenones did not promote neurite outgrowth but when induced with a low concentration of NGF (5 ng mL(-1)), the neuritogenic activity was comparable to that of the positive control (50 ng mL(-1) of NGF). Hericenone E was able to stimulate NGF secretion which was two-fold higher than that of the positive control. The neuritogenesis process was partially blocked by the tyrosine kinase receptor (Trk) inhibitor, K252a, suggesting that the neuritogenic effect was not solely due to NGF. Hericenone E also increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Taken together, this study suggests that hericenone E potentiated NGF-induced neuritogenesis in PC12 cells via the MEK/ERK and PI3K/Akt pathways.

Neurite outgrowth stimulatory effects of myco­synthesized AuNPs from Hericium erinaceus (Bull.: Fr.) Pers. on pheochromocytoma (PC-12) cells

“…In the presence of 5 ng/mL of NGF, hericenones significantly increased the percentage of neurite-bearing cells compared with control cell, which had either hericenones alone or 5 ng/mL of NGF. 12 In contrast to this result, a polysaccharide purified from H. erinaceus mycelium enhanced neurite outgrowth of PC-12 cells, and…”

“…Our previous findings showed that Hericenone E isolated from H. erinaceus increased the phosphorylation of extracellular-signal regulated kinases and protein kinase B, potentiating nerve growth factor (NGF)-induced neuritogenesis in PC-12 cells via the MEK/ERK and PI3K/Akt pathways. 12 Similarly, Erinacine D isolated from the mycelium of H. erinaceus acted as a stimulator of NGF synthesis. 13 Because of the poor regenerative capacity of CNS, other methods like drugs, gene therapy, stem cells therapy, and nanotechnology continue to be very active with significant clinical potential.…”

“…A previous study revealed that the compound hericenone isolated from H. erinaceus triggered ERK1/2 and PI3K/Akt signaling cascades. 12 Similarly, α-Phenyl-N-tert-butylnitron was also found to induce neurite outgrowth in PC-12 independent of TrkA. 44 Our previous study reported that Hericenone E is a neurotrophic compound that potentiates NGF-induced neurite outgrowth in PC-12 cells.…”

Restoration of sensory dysfunction following peripheral nerve injury by the polysaccharide from culinary and medicinal mushroom, Hericium erinaceus (Bull.: Fr.) Pers. through its neuroregenerative action

“…Phan et al (2014) isolated four benzyl alcohol derivatives namely hericenones B-E from the fruit bodies of H. erinaceus cultivated in tropical conditions in Malaysia. Hericenone E exerts neurotrophic activity in PC12 cells, and this activity is mediated by extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) signaling pathways.…”

“…The mushroom has been extensively tested in in vitro trials as the neurite outgrowth stimulator in the cultured cells of neural hybrid clone NG108-15 and rat phechromocytoma PC12 in our Fungal Biotechnology laboratory, Mushroom Research Centre, Faculty of Science (Wong et al, 2007;Lai et al, 2013;Phan et al, 2014). Phan et al (2014) isolated four benzyl alcohol derivatives namely hericenones B-E from the fruit bodies of H. erinaceus cultivated in tropical conditions in Malaysia.…”