Buyang Huanwu Decoction (BYHWD) Enhances Angiogenic Effect of Mesenchymal Stem Cell by Upregulating VEGF Expression After Focal Cerebral Ischemia.

Buyang Huanwu decoction (BYHWD) has been used for centuries to treat paralysis and stroke. Previously, we have demonstrated that BYHWD combined with mesenchymal stem cell (MSC) transplantation attenuates ischemic injury partly by upregulating angiogenesis. However, the mechanisms of this drug for stroke treatment are not completely understood. Here, we aimed to clarify the mechanism of BYHWD on angiogenesis mediated by MSCs. Firstly, we verified microvessels with a size of 50-100 nm produced by either MSCs or MSCs treated by 500 μg/ml BYHWD. These exosomes were purified and found to be able to activate vascular endothelial growth factor (VEGF) expression in endothelial cells (ECs). Moreover, exosomes from MSCs and MSCs treated by BYHWD induced elevated microRNA (miRNA)-126 expression and reduced miR-221 and miR-222 expression. In MSCs, disruption of dicer, an enzyme responsible for miRNA maturation, by dicer small interfering RNA (siRNA), or RNase pretreatment abolished this ability of the exosomes. Additionally, exosomes from MSCs treated by BYHWD promoted VEGF and Ki-67 expression and augmented vascular density in rat brain after bilateral carotid artery ligation. In conclusion, our study revealed that BYHWD exposure augmented angiogenetic miRNA and VEGF expression in exosomes secreted by MSCs and elevated angiogenesis in rat brain.