Houshiheisan promotes angiogenesis via HIF-1α/VEGF and SDF-1/CXCR4 pathways: in vivo and in vitro.

Abstract

RATIONALE:

Houshiheisan (HSHS), a classic prescription in traditional Chinese medicine (TCM), has remarkable efficacy in the treatment of ischemic stroke.

OBJECTIVE:

To investigate the pro-angiogenic effect and molecular mechanism of HSHS for stroke recovery.

METHODS AND RESULTS:

The rat permanent middle cerebral artery occlusion (pMCAO) model was constructed by suture method, HSHS (5.25 or 10.5 g/kg) and Ginaton (28 mg/kg) treatment was intragastrically administrated at 6 h after modeling which remained for 7 consecutive days. Pathological evaluation conducted by Hematoxylin-Eosin (HE) staining and the results showed that HSHS alleviated blood vessel edema, reduced the damage to blood vessels and neurons in the ischemic areas. Immunostaining, quantitative real-time fluorescence PCR results showed that HSHS up-regulated pro-angiogenic factors including platelet endothelial cell adhesion molecule-1 (cluster of differentiation 31 (CD31)), vascular endothelial growth factor (VEGF), vascular endothelial growth factor A (VEGFA), VEGF receptor 2 (VEGFR2), angiopoietin-1 (Ang-1), while down-regulated angiopoietin-2 (Ang-2), stromal cell derived factor-1 (SDF-1), and cxc chemokine receptor 4 (CXCR4) expression in infarct rat cortex, and similar results were obtained in subsequent Western blot experiment. Furthermore, CCK8 assay and transwell migration assay were performed to assess cell proliferation, migration, and tube formation. The medicated serum (MS) of HSHS appeared to have beneficial effects for immortalized human umbilical vein cells (Im-HUVECs) on proliferation and migration after persistence hypoxia. Western blot analysis revealed that the expression of hypoxia inducible factor-1α (HIF-1α), VEGFA, Ang-1, Ang-2, and CXCR4 were significantly up-regulated while Ang-2 was down-regulated by HSHS MS treatment compared with vehicle group in vitro.

CONCLUSION:

The present study suggests a novel application of HSHS as an effective angiogenic formula for stroke recovery.

• Authors: Yangyang Xiang, Xiaoquan Yao, Xuan Wang, Hui Zhao, Haiyan Zou, Lei Wang, Qiu-Xia Zhang
• Journal: Bioscience reports (Biosci Rep) Vol. 39 Issue 10 (10 30 2019) ISSN: 1573-4935 [Electronic] England
• PMID: 31652450 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Author(s).

Chemical References

• CXCL12 protein, rat
• Chemokine CXCL12
• Cxcr4 protein, rat
• Hif1a protein, rat
• Hypoxia-Inducible Factor 1, alpha Subunit
• Receptors, CXCR4
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, rat

Topics

• Animals
• Brain Ischemia (drug therapy, metabolism, pathology)
• Chemokine CXCL12 (metabolism)
• Disease Models, Animal
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Male
• Medicine, Chinese Traditional
• Neovascularization, Physiologic (drug effects)
• Rats
• Rats, Sprague-Dawley
• Receptors, CXCR4 (metabolism)
• Signal Transduction (drug effects)
• Stroke (drug therapy, metabolism, pathology)
• Vascular Endothelial Growth Factor A (metabolism)