The saponin DT-13 attenuates tumor necrosis factor-?-induced vascular inflammation associated with Src/NF-?B/MAPK pathway modulation.

ABSTRACT: This study aimed to explore the effect of DT-13 (25(R,S)-ruscogenin- 1-O- [?-d-glucopyranosyl- (1?2)][?-d-xylopyranosyl-(1?3)]-? -d- fucopyranoside) on tumor necrosis factor (TNF)-?-induced vascular inflammation and the potential molecular mechanisms. In vitro, DT-13 suppressed TNF-?-induced adhesion and migration of human umbilical vein endothelial cells (HUVECs) by inhibiting the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). DT-13 markedly suppressed NF-?B p65 phosphorylation, and when NF-?B p65 was over-expressed, the inhibitory effect of DT-13 on adhesion molecular decreased. DT-13 also suppressed TNF-? induced luciferase activities of ICAM-1 and VCAM-1 promoter containing NF-?B binding sites. Furthermore, DT-13 markedly suppressed p38 phosphorylation and Src degradation induced by TNF-?, whereas had no significant effect on ERK and JNK activation. In vivo, DT-13 at 4 mg/kg prevented vascular inflammation and the expression of adhesion molecules induced by TNF-? in mice. These findings suggest that DT-13 abrogates vascular inflammation by down-regulating adhesion molecules associated with modulating the NF-?B, p38MAPK, Src signaling pathways, and NF-?B binding site is at least one of the targets of DT-13. This study provides novel information regarding the mechanism by which DT-13 exerts its effects on vascular inflammation, which is important for the onset and progression of various diseases.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC4495414 | biostudies-other | 2015

REPOSITORIES: biostudies-other