Catalpol protects vascular structure and promotes angiogenesis in cerebral ischemic rats by targeting HIF-1α/VEGF
| Autor: | Xiao-gang Xu, Yue Yin, Hong-Jin Wang, Qiang Xue, Xiao-yu Xu, Huijing Ren, Shi-qi Yu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Angiogenesis Iridoid Glucosides Ischemia Pharmaceutical Science Neovascularization Physiologic Pharmacology Brain Ischemia Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Drug Discovery medicine Animals Stroke Cells Cultured 030304 developmental biology Tube formation 0303 health sciences business.industry Brain Endothelial Cells medicine.disease Hypoxia-Inducible Factor 1 alpha Subunit Catalpol In vitro Vascular endothelial growth factor Oxygen Glucose Complementary and alternative medicine chemistry 030220 oncology & carcinogenesis Molecular Medicine business |
| Zdroj: | Phytomedicine : international journal of phytotherapy and phytopharmacology. 78 |
| ISSN: | 1618-095X |
| Popis: | Background The initial factor in the occurrence, development, and prognosis of cerebral ischemia is vascular dysfunction in the brain, and vascular remodeling of the brain is the key therapeutic target and strategy for ischemic tissue repair. Catalpol is the main active component of the radix of Rehmannia glutinosa Libosch, and it exhibits potential pleiotropic protective effects in many brain-related diseases, including stroke. Purpose The present study was designed to investigate whether catalpol protects vascular structure and promotes angiogenesis in cerebral ischemic rats and to identify its possible mechanisms in vivo and in vitro. Study design Cerebral ischemic rats and oxygen-glucose deprivation-exposed brain microvascular endothelial cells were used to study the therapeutic potential of catalpol in vivo and in vitro. Methods First, neurological deficits, histopathological morphology, infarct volume, vascular morphology, vessel density, and angiogenesis in focal cerebral ischemic rats were observed to test the potential treatment effects of catalpol. Then, oxygen-glucose deprivation-exposed brain microvascular endothelial cells were used to mimic the pathological changes in vessels during ischemia to study the effects and possible mechanisms of catalpol in protecting vascular structure and promoting angiogenesis. Results The in vivo results showed that catalpol reduced neurological deficit scores and infarct volume, protected vascular structure, and promoted angiogenesis in cerebral ischemic rats. The in vitro results showed that catalpol improved oxygen-glucose deprivation-induced damage and promoted proliferation, migration, and in vitro tube formation of brain microvascular endothelial cells. The HIF-1α (hypoxia-inducible factor 1α)/VEGF (vascular endothelial growth factor) pathway was activated by catalpol both in the brains of cerebral ischemic rats and in primary brain microvascular endothelial cells, and the activating effects of catalpol were inhibited by SU1498. Conclusion The results of both the in vivo and in vitro studies proved that catalpol protects vascular structure and promotes angiogenesis in focal cerebral ischemic rats and that the mechanism is dependent on HIF-1α/VEGF. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect