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

Abstract

This study aimed to explore the effect of DT-13 (25(R,S)-ruscogenin- 1-O- [β-d-glucopyranosyl- (1→2)][β-d-xylopyranosyl-(1→3)]-β -d- fucopyranoside) on tumor necrosis factor (TNF)-α-induced vascular inflammation and the potential molecular mechanisms. In vitro, DT-13 suppressed TNF-α-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-кB p65 phosphorylation, and when NF-кB p65 was over-expressed, the inhibitory effect of DT-13 on adhesion molecular decreased. DT-13 also suppressed TNF-α induced luciferase activities of ICAM-1 and VCAM-1 promoter containing NF-κB binding sites. Furthermore, DT-13 markedly suppressed p38 phosphorylation and Src degradation induced by TNF-α, 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-α in mice. These findings suggest that DT-13 abrogates vascular inflammation by down-regulating adhesion molecules associated with modulating the NF-кB, p38MAPK, Src signaling pathways, and NF-κB 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.

• Authors: Yuanyuan Zhang, Minhui Sun, Yuwei Han, Kefeng Zhai, Youmei Tang, Xiaoying Qin, Zhengyu Cao, Boyang Yu, Junping Kou
• Journal: International journal of biological sciences (Int J Biol Sci) Vol. 11 Issue 8 Pg. 970-81 ( 2015) ISSN: 1449-2288 [Electronic] Australia
• PMID: 26157351 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Saponins
• Tumor Necrosis Factor-alpha
• ruscogenin-1-O-(glucopyranosyl-(1-2))(xylopyranosyl-(1-3))fucopyranoside
• src-Family Kinases

Topics

• Animals
• Cell Adhesion (drug effects)
• Cell Movement (drug effects)
• MAP Kinase Signaling System
• Mice
• NF-kappa B (metabolism)
• Phosphorylation
• Saponins (pharmacology)
• Tumor Necrosis Factor-alpha (physiology)
• Vasculitis (physiopathology, prevention & control)
• src-Family Kinases (metabolism)