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

Background: The induced neural stem cells (iNSCs) held great promises for cell replacement therapy, but iNSCs modulation need improvement. Matrix stiffness could control stem cell fates and might be effective to iNSCs modulations. Here the stiffness of hydrogel matrix on the adhesion, proliferation and differentiation of iNSCs were studied.Methods: Hyaluronic acid (HA) hydrogels with gradient stiffness were prepared. The structure and stiffness of hydrogels were detected by scanning electron microscopy (SEM) and rheological test. iNSCs were generated from human blood mononuclear cells and cultured in the hydrogels. The cell adhesion, proliferation and differentiation on gradient stiffness hydrogels were examined by CCK-8 test and immunofluorescence staining.Results: All hydrogels showed typical soft tissue, with the elastic modulus increasing with concentration (0.6-1.8%), ranging from 17 to 250 Pa. The iNSCs maintained growth and differentiation on all gels, but showed different behaviors to different stiffness. On the softer hydrogels, cells grew slowly at first but continuously and fast for long term, tending to differentiate into neurons; while on the harder hydrogels, cells adhered and grew faster at the early stage, tending to differentiate into glia cells after long term culture. Conclusions:The results suggested that hydrogels stiffness could regulate the key cellular processes of iNSCs. It was important for iNSCs modulation and application in the future.

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