Baicalin regulates neuronal fate decision in neural stem/progenitor cells and stimulates hippocampal neurogenesis in adult rats.

BACKGROUND: Recent studies revealed that baicalin, a flavonoid compound derived from the root of Scutellaria baicalensis Georgi, could promote neuron differentiation of NSPCs after commencing the differentiation process in vitro. However, this may not be the most efficacious strategy to determinate cell fate. Here, we have investigated whether baicalin can influence early events of neuron generation and stimulate adult neurogenesis. RESULTS: Transient exposure of NSPCs to baicalin during proliferation could activate Mash1 to alter the differential fate and increase the proportion of cells expressing neuronal markers. Seven days after, rats were exposed to transient cerebral ischemia, they were treated for 3 weeks with baicalin, BrdU labeling study showed that exposure to baicalin increased the number of newly generated cells in hippocampus, BrdU/NeuN double staining analysis indicated that baicalin could promote new neuron production after cerebral ischemia. Additionally, Morris water maze test showed that delayed postischemic treatment with baicalin improved cognitive impairment. CONCLUSIONS: These results identify the existence of a single molecule, baicalin, which can specify the neuronal fate of multipotent NSPCs and stimulate neurogenesis, making it a promising candidate for developing clinically relevant strategies to manipulate neuronal fate of NSPCs for brain repair.

Direct stimulation of adult neural stem/progenitor cells in vitro and neurogenesis in vivo by salvianolic acid B.

BACKGROUND: Small molecules have been shown to modulate the neurogenesis processes. In search for new therapeutic drugs, the herbs used in traditional medicines for neurogenesis are promising candidates. METHODOLOGY AND PRINCIPAL FINDINGS: We selected a total of 45 natural compounds from Traditional Chinese herbal medicines which are extensively used in China to treat stroke clinically, and tested their proliferation-inducing activities on neural stem/progenitor cells (NSPCs). The screening results showed that salvianolic acid B (Sal B) displayed marked effects on the induction of proliferation of NSPCs. We further demonstrated that Sal B promoted NSPCs proliferation in dose- and time-dependent manners. To explore the molecular mechanism, PI3K/Akt, MEK/ERK and Notch signaling pathways were investigated. Cell proliferation assay demonstrated that Ly294002 (PI3K/Akt inhibitor), but neither U0126 (ERK inhibitor) nor DAPT (Notch inhibitor) inhibited the Sal B-induced proliferation of cells. Western Blotting results showed that stimulation of NSPCs with Sal B enhanced the phosphorylation of Akt, and Ly294002 abolished this effect, confirming the role of Akt in Sal B mediated proliferation of NSPCs. Rats exposed to transient cerebral ischemia were treated for 4 weeks with Sal B from the 7th day after stroke. BrdU incorporation assay results showed that exposure Sal B could maintain the proliferation of NSPCs after cerebral ischemia. Morris water maze test showed that delayed post-ischemic treatment with Sal B improved cognitive impairment after stroke in rats. SIGNIFICANCE: Sal B could maintain the NSPCs self-renew and promote proliferation, which was mediated by PI3K/Akt signal pathway. And delayed post-ischemic treatment with Sal B improved cognitive impairment after stroke in rats. These findings suggested that Sal B may act as a potential drug in treatment of brain injury or neurodegenerative diseases.