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Int J Biol Sci 2015; 11(8):970-981. doi:10.7150/ijbs.11635

Research Paper

The saponin DT-13 Attenuates Tumor Necrosis Factor-α-induced Vascular Inflammation Associated with Src/NF-кB/MAPK Pathway Modulation

Yuanyuan Zhang#, Minhui Sun#, Yuwei Han, Kefeng Zhai, Youmei Tang, Xiaoying Qin, Zhengyu Cao, Boyang Yu, Junping Kou

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.)

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.

Keywords: DT-13, Endothelial inflammation, NF-кB, Src, MAPKs

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How to cite this article:
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