Buyang Huanwu Decoction Promotes Angiogenesis after Cerebral Ischemia by Inhibiting the Nox4/ROS Pathway.

BACKGROUND: Buyang Huanwu decoction (BYHWD), an important traditional Chinese medicine (TCM), has been used clinically for centuries for the treatment of various diseases. The study aims to explore the BYHWD effects on angiogenesis and neuroprotection after cerebral ischemia/reperfusion (CI/R) injury in rats and to explore the underlying angiogenic roles and mechanisms of BYHWD in hydrogen peroxide (H2O2) induced oxidative stress in human umbilical vein endothelial cells (HUVECs) model. METHODS: The effects of BYHWD on neurological function were screened by measuring neurological deficits, spatial memory function, and angiogenesis (by microvascular density (MVD) and cerebral blood flow (CBF)) after CI/R injury in middle cerebral artery occlusion (MCAO) in vivo in rats. In vitro, we examined the angiogenic roles and mechanisms of action of BYHWD in an H2O2-induced oxidative stress HUVECs model by measuring cell viability, apoptosis, vascular tube formation, intracellular ROS generation, NADPH oxidase (Nox) activity, and Nox4 protein expression. RESULTS: BYHWD significantly improved neurological function, including neurological deficits and spatial learning and memory, and significantly increased MVD and CBF in the ischemic penumbra after CI/R injury in rats. BYHWD significantly increased cell viability, inhibited apoptosis, induced vascular tube formation, decreased intracellular ROS generation, and reduced Nox activity and Nox4 protein expression in H2O2-treated HUVECs in a dose-dependent manner. CONCLUSIONS: Our study demonstrates that BYHWD promotes neurological function recovery and increases angiogenesis. BYHWD exerts angiogenic effects against cerebral ischemic injury through the downregulation of Nox4, which results in the reduction of ROS generation.

Buyang Huanwu Decoction attenuates H2O2-induced apoptosis by inhibiting reactive oxygen species-mediated mitochondrial dysfunction pathway in human umbilical vein endothelial cells.

BACKGROUND: Apoptosis of endothelial cells caused by reactive oxygen species plays an important role in ischemia/reperfusion injury after cerebral infarction. Buyang Huanwu Decoction (BYHWD) has been used to treat stroke and stroke-induced disability, however, the mechanism for this treatment remains unknown. In this study, we investigated whether BYHWD can protect human umbilical vein endothelial cells (HUVECs) from H2O2-induced apoptosis and explored the underlying mechanisms. METHODS: To investigate the effect of BYHWD on the apoptosis of HUVECs, we established a H2O2-induced oxidative stress model and detected apoptosis by Hoechst 33342 and propidium iodide staining. JC-1 and DCFH-DA assays,western blotting and electron microscopy were used to examine the mechanism of BYHWD on apoptosis. RESULTS: Pretreatment with BYHWD significantly inhibited H2O2-induced apoptosis and protein caspase-3 expression in a concentration-dependent manner. In addition, BYHWD reduced reactive oxygen species production and promoted endogenous antioxidant defenses. Furthermore, loss of mitochondrial membrane potential and structural disruption of mitochondria were both rescued by BYHWD. CONCLUSIONS: BYHWD protects HUVECs from H2O2-induced apoptosis by inhibiting oxidative stress damage and mitochondrial dysfunction. These findings indicate that BYHWD is a promising treatment for cerebral ischemia diseases.

Buyang Huanwu decoction increases angiopoietin-1 expression and promotes angiogenesis and functional outcome after focal cerebral ischemia.

Buyang Huanwu decoction (BYHWD), a traditional Chinese herbal prescription, has been widely used clinically to treat stroke in China for hundreds of years; however, the mechanisms of this drug for stroke treatment are still unclear. This study aims to observe the cerebral angiogenesis effects of BYHWD on chronic brain injury after focal cerebral ischemia in rats and to explore its possible mechanisms. The ischemia was induced by occlusion of the right middle cerebral artery for 90 min. BYHWD (12.5 and 25.0 g/(kg ∙ d), equivalent to the dry weight of the raw materials) was orally administered twice a day beginning 2 h after surgery. BYHWD significantly attenuated the neurological dysfunction, infarct volume, and brain atrophy after ischemia. There was a significant increase in the microvessel density, as assessed by immunofluorescence CD31, and a significant increase in angiopoietin-1 (Ang-1) in the penumbra areas of the rats was shown by immunohistochemical staining and Western blotting. The results indicate that the neurorestorative effects of BYHWD are associated with angiogenesis and the enhancement of the expressions of Ang-1 on chronic brain injury after focal cerebral ischemia.