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

Abstract

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.

Regenerative repair of Pifithrin-α in cerebral ischemia via VEGF dependent manner

“…We have previously observed that PFT-α inhibited p53 function in vivo by blockade of the translocation of p53 to the nucleus, either 14 . Based upon these results, we demonstrated that PFT-α increased the expression of VEGF, a protein which is upregulated 39 and leads to angiogenesis 15 in cerebral ischemia and neurogenesis in depressive disorders 40 . Since upregulation of VEGF promoted angiogenesis and neurogenesis, which further improved physiological functions after cerebral ischemic injury 41 , it is reasonable to propose that PFT-α promotes neurogenesis and angiogenesis, at least in part, through the upregulation of VEGF expression.…”

Adult Stem Cell Therapy for Stroke: Challenges and Progress

“…Transplantation of MSCs over-expressing miR-126, promotes functional angiogenesis in the ischemic myocardium [ 89 ]. In addition, modification of EV-miRs may occur during the ex vivo manipulation of stem cells, e.g., preconditioning [ 90 , 91 ].…”

Angiogenesis in Ischemic Stroke and Angiogenic Effects of Chinese Herbal Medicine

“…Results from pervious clinical studies have shown that BYHWD improved neurological functions in cerebral infraction patients, which has been suggested to be associated with an increased serum VEGF expression [ 107 ]. In an animal study, BYHWD combined with mesenchymal stem cells transplantation increased cerebral vascular density in rat brain after bilateral carotid artery ligation via an augmentation of VEGF and Ki-67b expressions induced by exosomes in endothelial cells [ 108 ]. Similarly, BYHWD has been shown to promote neurological recovery and angiogenesis via VEGFR-2 activation through the PI3K/Akt signalling pathway in a mouse model of intracerebral haemorrhage [ 109 ].…”