1. Academic Validation
  2. Catalpol protects vascular structure and promotes angiogenesis in cerebral ischemic rats by targeting HIF-1α/VEGF

Catalpol protects vascular structure and promotes angiogenesis in cerebral ischemic rats by targeting HIF-1α/VEGF

  • Phytomedicine. 2020 Nov;78:153300. doi: 10.1016/j.phymed.2020.153300.
Hongjin Wang 1 Xiaogang Xu 1 Yue Yin 1 Shiqi Yu 1 Huijing Ren 1 Qiang Xue 2 Xiaoyu Xu 3
Affiliations

Affiliations

  • 1 College of Pharmaceutical Sciences & Chinese Medicine, Southwest University, Chongqing 400715, China; Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Chongqing 400715, China; Pharmacology of Chinese Materia Medica - the Key Discipline Constructed by the State Administration of Traditional Chinese Medicine, Chongqing 400715, China.
  • 2 Chongqing Medical and Pharmaceutical College, Chongqing 401331, China. Electronic address: ygzxq3@sina.com.
  • 3 College of Pharmaceutical Sciences & Chinese Medicine, Southwest University, Chongqing 400715, China; Chongqing Key Laboratory of New Drug Screening from Traditional Chinese Medicine, Chongqing 400715, China; Pharmacology of Chinese Materia Medica - the Key Discipline Constructed by the State Administration of Traditional Chinese Medicine, Chongqing 400715, China; Southwest University Hospital, Chongqing 400715, China. Electronic address: xuxiaoyu@swu.edu.cn.
Abstract

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.

Keywords

Brain microvascular endothelial cells; Catalpol; Cerebral ischemia; Cerebral vessels; HIF-1α/VEGF.

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