A comparative study on inhibition of total astragalus saponins and astragaloside IV on TNFR1-mediated signaling pathways in arterial endothelial cells.
PLoS One
; 9(7): e101504, 2014.
Article
in En
| MEDLINE
| ID: mdl-24991819
ABSTRACT
BACKGROUND:
Both total astragalus saponins (AST) and it's main component astragaloside IV (ASIV) have been used in China as cardiovascular protective medicines. However, the anti-inflammatory activities that are beneficial for cardiovascular health have never been compared directly and the molecular mechanisms remain unresolved. This study was conducted to compare the inhibitory effects of these drugs on TNFα-induced cell responses, related signaling pathways, and the underlying mechanisms in mouse arterial endothelial cells. METHODOLOGY/PRINCIPALFINDINGS:
Real-time qRT-PCR was performed to determine the expression of cell adhesion molecule (CAM) genes. Immunofluorescent staining was used to detect the nuclear translocation of transcription factor NF-κB-p65. Western Blot analysis was used to identify TNFα-induced NF-κB-p65 phosphorylation, IκBα degradation, and caspase-3 cleavage. Cell surface proteins were isolated and TNFα receptor-1(TNFR1) expression was determined. The results suggest that both AST and ASIV attenuate TNFα-induced up-regulation of CAMs mRNA and upstream nuclear translocation and phosphorylation of NF-κB-p65. However, TNFR1-mediated IκBα degradation, cleavage of caspase-3 and apoptosis were inhibited only by AST. These differences in the actions of AST and ASIV could be explained by the presence of other components in AST, such as ASII and ASIII, which also had an inhibitory effect on TNFR1-induced IκBα degradation. Moreover, AST, but not ASIV, was able to reduce TNFR1 protein level on the cell surface. Furthermore, mechanistic investigation demonstrated that TNFR1-mediated IκBα degradation was reversed by the use of TAPI-0, an inhibitor of TNFα converting enzyme (TACE), suggesting the involvement of TACE in the modulation of surface TNFR1 level by AST.CONCLUSION:
ASIV was not a better inhibitor than AST, at least on the inhibition of TNFα-induced inflammatory responses and TNFR1-mediated signaling pathways in AECs. The inhibitory effect of AST was caused by the reduction of cell surface TNFR1 level, and TACE could be involved in this action.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Saponins
/
Triterpenes
/
Signal Transduction
/
Astragalus Plant
/
Endothelial Cells
/
Receptors, Tumor Necrosis Factor, Type I
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2014
Document type:
Article
Affiliation country:
China
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA