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

Discovery and isolation of compounds capable of blocking the interactions between VCAM-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 Bupleurum falcatum L. Their structures were elucidated by spectroscopic analysis (1H-, 13C-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 of THP-1 cells with respective IC50 values of 7.8 and 1.7 μM. The aglycone structure of 2 also showed cell adhesion inhibitory activity with an IC50 value of 21.1 μM. With these results, we suspect these two saikosaponins from the Bupleurum falcatum L. roots to be prime candidates for therapeutic strategies towards inflammation. KCI Citation Count: 2