losartan-potassium and catalpol

Catalpol is the main active component of the radix from Rehmannia glutinosa Libosch, which has pleiotropic protective effects in neurodegenerative diseases, ischemic stroke, metabolic disorders and others. Catalpol has been shown to have neuroprotective, neurorepair, and angiogenesis effects following ischemic brain injury. However, its molecular mechanisms are still poorly understood. In previous studies, the JAK2/STAT3 signaling pathway was found to play a role in neuroprotection and angiogenesis. This study investigated the role of catalpol in stimulating angiogenesis via the JAK2/STAT3 pathway after permanent focal cerebral ischemia (pMCAO).. Rats were subjected to right middle cerebral artery occlusion through electrocoagulation and were treated with catalpol (5mg/kg), AG490 was also used to inhibit STAT3 phosphorylation (pSTAT3).. Following stroke, Catalpol improved the neuroethology deficit, increased the cerebral blood flow (CBF) of infarcted brain and upregulated EPO and EPOR. AG490 suppressed the phosphorylation of signal transducer and activator of transcription 3 (STAT3), ultimately inhibited VEGF mRNA expression, which reduced VEGF protein expression and inhibited stroke-induced angiogenesis. However, Catalpol enhanced stroke-induced STAT3 activation and subsequently restored STAT3 activity through the recovery of STAT3 binding to VEGF. Moreover, Catalpol reversed the effect of AG490 on STAT3 activation and nuclear translocation, restored the transcriptional activity of the VEGF promoter by recruiting STAT3 to the VEGF promoter, improved VEGF mRNA and protein expression, increased angiogenesis, reduced the difference in CBF between the infarcted and intact brain and ameliorated the neuroethology behaviors after stroke.. Catalpol affects neuroprotection and angiogenesis via the JAK2/STAT3 signaling pathway, which is mediated by STAT3 activation and VEGF expression. Catalpol may be used as a potential therapeutic drug for stroke.

Topics: Angiogenesis Inducing Agents; Animals; Brain; Cerebral Arteries; Cerebrovascular Circulation; Disease Models, Animal; Erythropoietin; Infarction, Middle Cerebral Artery; Iridoid Glucosides; Janus Kinase 2; Male; Neovascularization, Physiologic; Neuroprotective Agents; Phosphorylation; Promoter Regions, Genetic; Protein Binding; Rats, Sprague-Dawley; Receptors, Erythropoietin; RNA, Messenger; Signal Transduction; STAT3 Transcription Factor; Time Factors; Transcriptional Activation; Up-Regulation; Vascular Endothelial Growth Factor A

To investigate the role and mechanism of catalpol in brain angiogenesis in a rat model of stroke, the effect of catalpol (5 mg/kg; i.p) or vehicle administered 24 hours after permanent middle cerebral artery occlusion (pMCAO) on behavior, angiogenesis, ultra-structural integrity of brain capillary endothelial cells, and expression of EPO and VEGF were assessed. Repeated treatments with Catalpol reduced neurological deficits and significantly improved angiogenesis, while significantly increasing brain levels of EPO and VEGF without worsening BBB edema. These results suggested that catalpol might contribute to infarcted-brain angiogenesis and ameliorate the edema of brain capillary endothelial cells (BCECs) by upregulating VEGF and EPO coordinately.

Topics: Animals; Blotting, Western; Endothelial Cells; Erythropoietin; Heart; Immunohistochemistry; Infarction, Middle Cerebral Artery; Iridoid Glucosides; Male; Myocardium; Neovascularization, Physiologic; Psychomotor Performance; Rats; Rats, Sprague-Dawley; Up-Regulation; Vascular Endothelial Growth Factor A