Buyang Huanwu Decoction can promote the proliferation of neural progenitor cell and neurogenesis induced by ischemia stroke via Jak2/stat3-hes1 crosstalk

Abstract

OBJECTIVES: Buyang Huanwu Decoction (BHD), a classic traditional Chinese medicine (TCM) formula, has been used for recovering neurological dysfunctions and treating post-stroke disability in China for about 200 years. The molecular mechanisms are still unknown. In order to explore the molecular mechanisms of the formula for stroke treatment, we investigated the effects of BHD on modulating cellular growth signals and improving neural stem cells proliferation and differentiation in the experimental rat stroke model by the occlusion of middle cerebral artery (MCAO). METHODS: BHD was orally administrated to the rats for 14and 28 days after MCAO. We detected the proliferation-promoting effects by immunofluorescent staining of thymidine analog 5-bromo-2′-deoxyuridine (BrdU). We also detected the differentiation-promoting effects by immunofluorescence double staining of doublecortin (DCX) and neuron-specific nuclear antigen (NeuN) and astrocyte marker (GFAP). To understand its mechanisms, we investigated the expressions of proteins involved in Jak/stat3 pathway and hes1 which is important signaling molecule to maintain the neural stem cells at the early stage and improve neurogenesis on the later period. RESULTS: The results showed that the formula stimulated the proliferation of the neural stem cells at dentate gyrus of hippocampus in the ischemic brains. BHD could increase the number of the double staining positive cells. We found the formula remarkably up-regulated the expressions of p-Jak, p-stats3, Cylin D1 and hes1 in vitro. CONCLUSION: These result indicated that BHD could improve the neural stem cell proliferation and differentiation, and the underlying mechanism were related to activate Jak/p-Stat3 -hes1 crosstalk.