PUBLICATION
Meisoindigo, but not its core chemical structure indirubin, inhibits zebrafish interstitial leukocyte chemotactic migration
- Authors
- Ye, B., Xiong, X., Deng, X., Gu, L., Wang, Q., Zeng, Z., Gao, X., Gao, Q., Wang, Y.
- ID
- ZDB-PUB-161217-3
- Date
- 2017
- Source
- Pharmaceutical biology 55: 673-679 (Journal)
- Registered Authors
- Keywords
- Meisoindigo, indirubin, inflammation, leukocyte chemotactic migration, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Anti-Inflammatory Agents/chemistry
- Anti-Inflammatory Agents/pharmacology*
- Chemotaxis, Leukocyte/drug effects*
- Disease Models, Animal
- Dose-Response Relationship, Drug
- Green Fluorescent Proteins/biosynthesis
- Green Fluorescent Proteins/genetics
- Indoles/chemistry
- Indoles/pharmacology
- Inflammation/immunology
- Inflammation/metabolism
- Inflammation/prevention & control*
- Leukocytes/drug effects*
- Leukocytes/immunology
- Leukocytes/metabolism
- Molecular Structure
- Signal Transduction/drug effects
- Structure-Activity Relationship
- Time Factors
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/immunology*
- Zebrafish/metabolism
- PubMed
- 27981893 Full text @ Pharm Biol
Citation
Ye, B., Xiong, X., Deng, X., Gu, L., Wang, Q., Zeng, Z., Gao, X., Gao, Q., Wang, Y. (2017) Meisoindigo, but not its core chemical structure indirubin, inhibits zebrafish interstitial leukocyte chemotactic migration. Pharmaceutical biology. 55:673-679.
Abstract
Context Inflammatory disease is a big threat to human health. Leukocyte chemotactic migration is required for efficient inflammatory response. Inhibition of leukocyte chemotactic migration to the inflammatory site has been shown to provide therapeutic targets for treating inflammatory diseases.
Objective Our study was designed to discover effective and safe compounds that can inhibit leukocyte chemotactic migration, thus providing possible novel therapeutic strategy for treating inflammatory diseases.
Materials and methods In this study, we used transgenic zebrafish model (Tg:zlyz-EGFP line) to visualize the process of leukocyte chemotactic migration. Then, we used this model to screen the hit compound and evaluate its biological activity on leukocyte chemotactic migration. Furthermore, western blot analysis was performed to evaluate the effect of the hit compound on the AKT or ERK-mediated pathway, which plays an important role in leukocyte chemotactic migration.
Results In this study, using zebrafish-based chemical screening, we identified that the hit compound meisoindigo (25 μM, 50 μM, 75 μM) can significantly inhibit zebrafish leukocyte chemotactic migration in a dose-dependent manner (p = 0.01, p = 0.0006, p < 0.0001). Also, we found that meisoindigo did not affect the process of leukocyte reverse migration (p = 0.43). Furthermore, our results unexpectedly showed that indirubin, the core structure of meisoindigo, had no significant effect on zebrafish leukocyte chemotactic migration (p = 0.6001). Additionally, our results revealed that meisoindigo exerts no effect on the Akt or Erk-mediated signalling pathway.
Discussion and conclusion Our results suggest that meisoindigo, but not indirubin, is effective for inhibiting leukocyte chemotactic migration, thus providing a potential therapeutic agent for treating inflammatory diseases.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping