Uridine from Pleurotus giganteus and Its Neurite Outgrowth Stimulatory Effects with Underlying MechanismReport as inadecuate




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Neurodegenerative diseases are linked to neuronal cell death and impairment of neurite outgrowth. An edible mushroom, Pleurotus giganteus was found to stimulate neurite outgrowth in vitro but the chemical constituents and the underlying mechanism is yet to be elucidated. The chemical constituents of P. giganteus linoleic acid, oleic acid, cinnamic acid, caffeic acid, p-coumaric acid, succinic acid, benzoic acid, and uridine were tested for neurite outgrowth activity. Uridine 100 μM was found to increase the percentage of neurite-bearing cells of differentiating neuroblastoma N2a cells by 43.1±0.5%, which was 1.8-fold higher than NGF 50 ng-mL-treated cells. Uridine which was present in P. giganteus 1.80±0.03 g-100g mushroom extract increased the phosphorylation of extracellular-signal regulated kinases ERKs and protein kinase B Akt. Further, phosphorylation of the mammalian target of rapamycin mTOR was also increased. MEK-ERK and PI3K-Akt-mTOR further induced phosphorylation of cAMP-response element binding protein CREB and expression of growth associated protein 43 GAP43; all of which promoted neurite outgrowth of N2a cells. This study demonstrated that P. giganteus may enhance neurite outgrowth and one of the key bioactive molecules responsible for neurite outgrowth is uridine.



Author: Chia-Wei Phan , Pamela David, Kah-Hui Wong, Murali Naidu, Vikineswary Sabaratnam

Source: http://plos.srce.hr/



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