Fuyuan Xingnao Decoction Promotes Angiogenesis Through the Rab1/AT1R Pathway in Diabetes Mellitus Complicated With Cerebral Infarction

Abstract

Fuyuan Xingnao decoction (FYXN), a traditional Chinese formula comprised of seven herbs, has been utilized to treat diabetes mellitus complicated with cerebral infarction (DMCI) for years. Yet, its protective and regulatory mechanism is poorly understood. The aim of the study is to investigate the effects of FYXN on DMCI in vitro and in vivo, as well as its mechanism in angiogenesis. For in vivo experiments, FYXN was administered to DMCI rats with streptozotocin (STZ) injection-induced diabetes. Then middle cerebral artery occlusion (MCAO) was conducted and the cerebral cortex sections of the rats were obtained. The ultrastructure of cerebral microvessels and new vessel density of ischemic penumbra were evaluated by the transmission electron microscopy (TEM) assay and immunohistochemistry, respectively. Protein and mRNA expression levels of Rab1/AT1R in cortex were assayed by Western blotting and real-time fluorescence quantitative real-time polymerase chain reaction (RT-qPCR). In vitro, FYXN serum was produced in rats on the fourth day 2 h after the last FYXN administration. Green fluorescence was observed after transfection with lentivirus packaged Rab1-WT or siRNA for 24 h. The activity of brain microvascular endothelial cells (BMECs) treated with sera from these rats was tested by MTT assay and Transwell assays, respectively. The expression of AT1R on the cell membrane and endoplasmic reticulum of BMECs was evaluated by immunofluorescence staining. Protein expression levels of signaling molecules in the Rab1/AT1R pathways were also detected. Results showed that in vivo, FYXN treatment significantly intensified CD31 staining in the cortical areas and enhanced the mRNA and protein levels of AT1R, Ang II, Rab1a, Rab1b and VEGF expression in ischemic cerebral cortex tissues. In vitro, the expression levels of AT1R, Ang II, Rab1a, Rab1b and VEGF in the cerebral infarction model group were significantly higher than those in the control group, with further increases after administration of FYXN drug serum. FYXN promoted the proliferation and migration of BMECs by activating the Rab1/AT1R signaling pathway. In conclusion, FYXN exerts a protective effect against DMCI by promoting angiogenesis via the Rab1/AT1R pathway, which provides strong evidence for the therapeutic effect of FYXN on DMCI.

Saposhnikoviae Radix Enhanced the Angiogenic and Anti-Inflammatory Effects of Huangqi Chifeng Tang in a Rat Model of Cerebral Infarction

“…MCAO is a typical model for studying CI [ 9 ]. In this study, a MCAO model was used to investigate the guiding and enhancing effects of SR on HQCFT in the treatment of CI.…”

“…The MCAO rat model was established according to previous studies [ 9 , 10 ]. Briefly, rats were deeply anesthetized with 3% pentobarbital sodium (45 mg/kg) by intraperitoneal injection.…”

Mitochondria-Endoplasmic Reticulum Crosstalk in Parkinson’s Disease: The Role of Brain Renin Angiotensin System Components

“…AT2R stimulation has been found to inhibit NADPH oxidase and reduces oxidative stress in PD [ 163 ]. ER is the hub of the protein machinery; reports indicate that AT1R synthesized and assembled in the ER is transported to the Golgi complex for post- translational modifications [ 164 ]. Although these data provide a wider arena for identifying AT1/2 receptors on the ER, possibly in DA neurons, the molecular mechanism behind the trafficking of AT1R from the ER to the cell surface remains largely unknown, especially in PD.…”

Identification of an miRNA Regulatory Network and Candidate Markers for Ischemic Stroke Related to Diabetes

“…10 Ischemic stroke can induce or aggravate cerebrovascular damage, especially in diabetic patients under 65 years old. 11 Antihypertensive, antiplatelet, and hypolipidemic agents can reduce the risk of ischemic stroke in diabetic patients, 12 but even with treatment, individuals with diabetes are at higher risk of cerebrovascular accidents than individuals without diabetes. 13 In fact, up to 80% of individuals with diabetes eventually die of macrovascular complications.…”

“…10 Ischemic stroke can induce or aggravate cerebrovascular damage, especially in diabetic patients under 65 years old. 11 …”