PUBLICATION
Discovery of anti-stroke active substances in Guhong injection based on multi-phenotypic screening of zebrafish
- Authors
- Wang, Y., Wu, H., Sheng, H., Wang, Y., Li, X., Wang, Y., Zhao, L.
- ID
- ZDB-PUB-220929-6
- Date
- 2022
- Source
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 155: 113744 (Journal)
- Registered Authors
- Keywords
- Active substances, Coagulation factors, Guhong injection, Inflammatory response, Phenotypic screening, Zebrafish
- MeSH Terms
-
- Animals
- Brain Ischemia*/metabolism
- Chlorogenic Acid/therapeutic use
- Cytokines/therapeutic use
- Gallic Acid/therapeutic use
- Ischemic Stroke*/drug therapy
- Mice
- Molecular Docking Simulation
- NF-kappa B/therapeutic use
- Phenylhydrazines/therapeutic use
- Plant Extracts/pharmacology
- Plant Extracts/therapeutic use
- Rats
- Rats, Sprague-Dawley
- Rutin/therapeutic use
- Stroke*/drug therapy
- Thrombosis*/drug therapy
- Zebrafish
- PubMed
- 36156365 Full text @ Biomed. Pharmacother.
Citation
Wang, Y., Wu, H., Sheng, H., Wang, Y., Li, X., Wang, Y., Zhao, L. (2022) Discovery of anti-stroke active substances in Guhong injection based on multi-phenotypic screening of zebrafish. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 155:113744.
Abstract
Ischemic stroke is a leading cause of death worldwide, and it remains an urgent task to develop novel and alternative therapeutic strategies for the disease. We previously reported the positive effects of Guhong injection (GHI), composed of safflower extract and aceglutamide, in promoting functional recovery in ischemic stroke mice. However, the active substances and pharmacological mechanism of GHI is still elusive. Aiming to identify the active anti-stroke components in GHI, here we conducted a multi-phenotypic screening in zebrafish models of phenylhydrazine-induced thrombosis and ponatinib-induced cerebral ischemia. Peripheral and cerebral blood flow was quantified endogenously in erythrocytes fluorescence-labeled thrombosis fish, and baicalein and rutin were identified as major anti-thrombotic substances in GHI. Moreover, using a high-throughput video-tracking system, the effects of locomotion promotion of GHI and its main compounds were analyzed in cerebral ischemia model. Chlorogenic acid and gallic acid showed significant effects in preventing locomotor dyfunctions. Finally, GHI treatment greatly decreased the expression levels of coagulation factors F7 and F2, NF-κB and its mediated proinflammatory cytokines in the fish models. Molecular docking suggested strong affinities between baicalein and F7, and between active substances (baicalein, chlorogenic acid, gallic acid, and rutin) and NF-κB p65. In summary, our findings established a novel drug discovery method based on multi-phenotypic screening of zebrafish, provided endogenous evidences of GHI in preventing thrombus formation and promoting behavioral recovery after cerebral ischemia, and identified baicalein, rutin, chlorogenic acid, and gallic acid as active compounds in the management of ischemic stroke.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping