Potentiation of neuritogenic activity of medicinal mushrooms in rat pheochromocytoma cells

Abstract

BackgroundSenescence of the neurons is believed to be a focal factor in the development of age-related neurodegenerative diseases such as Alzheimer’s disease. Diminutions in the levels of nerve growth factor (NGF) lead to major declines in brain cell performance. Functional foods, believed to mitigate this deficiency, will be reaching a plateau in the near future market of alternative and preventive medicine. In the search for neuroactive compounds that mimic the NGF activity for the prevention of neurodegenerative diseases, the potential medicinal values of culinary and medicinal mushrooms attract intense interest.MethodsCytotoxic effects of aqueous extracts of three medicinal mushrooms basidiocarps, Ganoderma lucidum, Ganoderma neo-japonicum and Grifola frondosa towards rat pheochromocytoma (PC-12) cells were determined by 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The potentiation of neuritogenic activity was assessed by neurite outgrowth stimulation assay. Involvement of cellular signaling pathways, mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK1/2) and phosphoinositide-3-kinase/protein kinase B (PI3K/Akt) in mushrooms-stimulated neuritogenesis were examined by using specific pharmacological inhibitors. Alteration of neuronal morphology by inhibitors was visualized by immunofluorescence staining of the neurofilament.ResultsAll the aqueous extracts tested caused a marked stimulation of neuritogenesis with no detectable cytotoxic effects towards PC-12 cells. The aqueous extract of G. neo-japonicum triggered maximal stimulation of neurite outgrowth at a lower concentration (50 μg/ml) with 14.22 ± 0.43% of neurite-bearing cells, compared to G. lucidum and G. frondosa that act at a higher concentration (75 μg/ml), with 12.61 ± 0.11% and 12.07 ± 0.46% of neurite-bearing cells, respectively. The activation of MEK/ERK1/2 and PI3K/Akt signaling pathways were necessary for the NGF and aqueous extracts to promote neuritogenesis.ConclusionsGanoderma lucidum, G. neo-japonicum and G. frondosa may contain NGF-like bioactive compound(s) for maintaining and regenerating the neuronal communications network. The present study reports the first evidence of the neuritogenic effects of aqueous extracts of basidiocarps of G. neo-japonicum in-vitro and showed the involvement of MEK/ERK1/2 and P13K/Akt signaling pathways for neuritogenesis in PC-12 cells.

An Antioxidant Dietary Supplement Improves Brain-Derived Neurotrophic Factor Levels in Serum of Aged Dogs: Preliminary Results

“…Grifola Frondosa is a culinary-medicinal mushroom that may play an important role in the prevention of many age-associated neurological dysfunctions, including Alzheimer's and Parkinson's diseases. The mushroom shows neuroprotective, antioxidant and anti-(neuro)inflammatory effects; in fact it reduces beta amyloid-induced neurotoxicity, neurite outgrowth stimulation, and nerve growth factor (NGF) synthesis [ 14 ]. It can be considered a useful therapeutic agent in the management and/or treatment of neurodegenerative diseases [ 15 ].…”

Lignosus rhinocerotis (Cooke) Ryvarden mimics the neuritogenic activity of nerve growth factor via MEK/ERK1/2 signaling pathway in PC-12 cells

“…Then, the supernatant was carefully replaced with freshly prepared extracts or crude polysaccharides (0–2500 μg/ml) in complete F-12 K medium. After 48 h of incubation, 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed as described previously 26 . The extent of the reduction of MTT was determined by measurement of the absorbance at 540 nm with 690 nm as background absorbance with an ELISA microplate reader (Sunrise, Tecan).…”

“… 24 , Pleurotus giganteus (Berk.) Karunarathna & K. D. Hyde 25 and Ganoderma neo-japonicum Imazeki 26 in PC-12 cells were mediated via MEK/ERK1/2 signaling pathway.…”

Emerging Roles of Ganoderma Lucidum in Anti-Aging

“…Comparing with G. lucidum , G. neo-japonicum is more effective in inducing neuritogenesis in PC12 cells. They induce this effect by mimicking NGF, which promotes neuronal survival and neuritogenesis [ 82 ]. Furthermore, the aqueous extracts of G. lucidum and G. neo-japonicum induce neuroprotection through the MEK/ERK1/2 and PI3K/Akt signaling pathways [ 81 ].…”