Inhibition of VLA-4/VCAM-1-mediated Cell Adhesion by Triterpenoid Saponins from Bupleurumfalcatum L

摘要

Discovery and isolation of compounds capable of blocking the interactions between VC AM-1 and VLA-4, a major pair of adhesion molecules contributing to the different steps of leukocyte migration across the endothelium in inflammatory responses, has been a major goal of this lab. Through bioactivity-guided fractionation, five saikosaponins were subsequently isolated from the methanol extracts of the roots of Bupleurumfalcatum L. Their structures were elucidated by spectroscopic analysis (~1H-, ~(13)C-NMR and 2D-NMR), as follows, saikosaponins: A (1); D (2); C (3); B3 (4); B4 (5). Compounds 1 and 2 inhibited interaction of sVCAM-1 and VLA-4 ofTHP-1 cells with respective IC_(50) values of 7.8 and 1.7 μM. The aglycone structure of 2 also showed cell adhesion inhibitory activity with an IC_(50) value of 21.1 μM. With these results, we suspect these two saikosaponins from the Bupleurumfalcatum L. roots to be prime candidates for therapeutic strategies towards inflammation.