PUBLICATION
Protective effects of puerarin against Aß40-induced vascular dysfunction in zebrafish and human endothelial cells
- Authors
- Lu, X.L., Liu, J.X., Wu, Q., Long, S.M., Zheng, M.Y., Yao, X.L., Ren, H., Wang, Y.G., Su, W.W., Fai Cheung, R.T., Zeng, J.S., Su, H., Pei, Z.
- ID
- ZDB-PUB-140513-231
- Date
- 2014
- Source
- European Journal of Pharmacology 732: 76-85 (Journal)
- Registered Authors
- Keywords
- Aß40, Puerarin, Vascular protection, Zebrafish
- MeSH Terms
-
- Amyloid beta-Peptides/antagonists & inhibitors*
- Amyloid beta-Peptides/toxicity*
- Animals
- Endothelial Cells/drug effects*
- Humans
- Isoflavones/pharmacology*
- Neovascularization, Physiologic/drug effects
- Neuroprotective Agents/pharmacology*
- Reactive Oxygen Species/metabolism
- Respiratory Burst/drug effects
- Vascular Diseases/chemically induced*
- Vascular Diseases/pathology
- Vascular Diseases/prevention & control*
- Zebrafish
- PubMed
- 24690262 Full text @ Eur. J. Pharmacol.
Citation
Lu, X.L., Liu, J.X., Wu, Q., Long, S.M., Zheng, M.Y., Yao, X.L., Ren, H., Wang, Y.G., Su, W.W., Fai Cheung, R.T., Zeng, J.S., Su, H., Pei, Z. (2014) Protective effects of puerarin against Aß40-induced vascular dysfunction in zebrafish and human endothelial cells. European Journal of Pharmacology. 732:76-85.
Abstract
Aβ40-induced vascular dysfunction has been implicated in the pathogenesis of Alzheimer's disease (AD). In the present study, we investigated the possible protective effects of puerarin against Aβ40-induced vascular damage and impairment to angiogenesis in transgenic TG (fli1:EGFP) zebrafish and human endothelial cells. Aβ40 peptides at 5 μM caused an obvious reduction of vessel branches in the subintestinal vein basket, induced NADPH oxidase-derived reactive oxygen species and impaired vascular endothelial growth factor (VEGF)-dependent angiogenesis. Pretreatment with puerarin attenuated Aβ40-induced vessel reduction and impairment to angiogenesis in a dose-dependent manner. In addition, Aβ40 decreased VEGF-dependent phosphorylation of Akt and eNOS, whereas puerarin treatment attenuated these detrimental effects. Furthermore, the restoration of Aβ40-induced-angiogenesis impairment by puerarin was abolished by either the PI3 kinase inhibitor LY294002 (10μM) or eNOS inhibitor L-NAME. The present study suggests that puerarin exerts its protective action probably through reduction of NADPH oxidase-derived reactive oxygen species overproduction and activation of the PI3K/Akt/eNOS pathways.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping