Modulatory Effects of Natural Products on Neuronal Differentiation

Neuron loss is the cardinal characteristic of neurodegenerative diseases. Regulation of adult neurogenesis, especially the induction of neuronal differentiation, is important in developing therapies to promote neuronal regeneration from nerve injury or neurological disorders. Neuronal differentiation is extremely complicated because it can occur in different cell types and be caused by a variety of inducers. In recent years, medicinal plant-derived natural compounds have received extensive attention as major sources of new therapeutic agents for treating neurological disorders and they exert their effects by promoting adult neurogenesis. In this study, we summarized the detailed research progress on the active natural compounds with potential neuroprotective effects and their molecular mechanisms on inducing neuronal differentiation and morphogenesis in NS/PCs, MSCs, PC12 cells and neuroblastoma cells. The active ingredients derived from natural plants that efficacious in promoting neuronal differentiation and neurite outgrowth include phenolics, flavonoids, alkaloids, coumarins, terpenes, quinines, glycosides, iridoids, volatile oils and others (xanthone, isothiocyanate). Studies have shown that above natural products exert the promotion effects via regulating many factors involve in the process of neurogenesis, including specific proteins (DCX, β IIItubulin, MAP-2, NSE, Tau, Nestin, GAP-43, Neurofilaments, GFAP), related genes and proteins (Stat3, Hes1, Mash1, NeuroD1, SIRT1, Hsp70, Reggie-1, Cyclin D1), transcription factors (CREB, Nkx-2.5, Ngn1), neurotrophins (BDNF, NGF, NT-3) and signaling pathways (JAK/STAT, Wnt/β- catenin, MEK-ERK1/2, PI3K/Akt, Akt/GSK-3β/β-catenin, PKA/GSK3β/β-catenin, Notch, BMP, Ca2+/CaMKII/ATF1, Nrf2/HO-1). The development of neuro-modulating natural products is of great value for the prevention or treatment of neurodegenerative diseases and for neuronal regenerative medicine.