Int J Biol Sci 2015; 11(8):970-981. doi:10.7150/ijbs.11635
The saponin DT-13 Attenuates Tumor Necrosis Factor-α-induced Vascular Inflammation Associated with Src/NF-кB/MAPK Pathway Modulation
Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, 639 Longmian Road, Nanjing 211198, China
# Co-first authors (Y.Z.,& M.S.)
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.
Keywords: DT-13, Endothelial inflammation, NF-кB, Src, MAPKs
Zhang Y, Sun M, Han Y, Zhai K, Tang Y, Qin X, Cao Z, Yu B, Kou J. The saponin DT-13 Attenuates Tumor Necrosis Factor-α-induced Vascular Inflammation Associated with Src/NF-кB/MAPK Pathway Modulation. Int J Biol Sci 2015; 11(8):970-981. doi:10.7150/ijbs.11635. Available from http://www.ijbs.com/v11p0970.htm