Neuroprotection of benzoinum in cerebral ischemia model rats via the ACE-AngI-VEGF pathway.

Abstract

AIMS:

Stroke is a devastating event with a limited choice of intervention. Benzoinum is frequently used to treat stroke in traditional Chinese medicine. Our team has found that the neuroprotection of benzoinum may related to angiogenesis, but the exact biological mechanism is unclear. The objective of this study was to explore its biological mechanism of angiogenesis in cerebral ischemia model rats.

MAIN METHODS:

First, network pharmacology and molecular docking were performed to predict the possible targets and mechanisms of benzoinum in treating ischemic stroke. The best dose was then selected according to pharmacodynamic indexes such as those for neurological deficit, cerebral infarction rate, and brain histopathology in middle cerebral artery occlusion (MCAO) model rats. Finally, RT-PCR, Western Blot and immunohistochemical analysis were applied to verify the prediction results from molecular docking.

KEY FINDINGS:

Network pharmacology and molecular docking demonstrated that the targets of treating cerebral ischemia were PDE4D, ACE and TTR, and the mechanism may be related to the ACE-AngI-VEGF signaling pathway. Experimental verification results suggested that 0.50 g/kg and 1.00 g/kg benzoinum could significantly protect against neurological deficit and reduce cerebral infarction rate in the cerebral cortex and hippocampus in MCAO model rats. At an optimal dose, benzoinum could significantly up-regulate VEGF, SHH and ANG-1, yet down-regulate ACE expression in MCAO model rats.

SIGNIFICANCE:

Balsamic acid is the active ingredient of benzoinum that protects against ischemic stroke and the possible mechanism is related to the promotion of angiogenesis via regulating ACE-AngI-VEGF pathway.

• Authors: Hai Chen, Mihong Ren, Hongyan Li, Qian Xie, Rong Ma, Yong Li, Xiaoqing Guo, Jian Wang, Daoyin Gong, Tian Gao
• Journal: Life sciences (Life Sci) Vol. 260 Pg. 118418 (Nov 01 2020) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 32931799 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• Neuroprotective Agents
• Small Molecule Libraries
• Vascular Endothelial Growth Factor A
• benzoinum
• vascular endothelial growth factor A, rat
• angiogenin
• Ribonuclease, Pancreatic
• Peptidyl-Dipeptidase A

Topics

• Animals
• Brain Ischemia (drug therapy, etiology, metabolism, pathology)
• Cerebral Cortex (drug effects, pathology)
• Disease Models, Animal
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Gene Expression Regulation (drug effects)
• Infarction, Middle Cerebral Artery (complications)
• Male
• Molecular Docking Simulation
• Neovascularization, Pathologic (drug therapy, metabolism, pathology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Peptidyl-Dipeptidase A (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (drug therapy, etiology, metabolism, pathology)
• Ribonuclease, Pancreatic (genetics, metabolism)
• Small Molecule Libraries (pharmacology)
• Stroke (drug therapy, etiology, metabolism, pathology)
• Vascular Endothelial Growth Factor A (genetics, metabolism)