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

Abstract

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 (<TEX>$^1H-$</TEX>, <TEX>$^{13}C$</TEX>-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 <TEX>$IC_{50}$</TEX> values of 7.8 and 1.7 <TEX>${\mu}M$</TEX>. The aglycone structure of 2 also showed cell adhesion inhibitory activity with an <TEX>$IC_{50}$</TEX> value of 21.1 <TEX>${\mu}M$</TEX>. With these results, we suspect these two saikosaponins from the Bupleurum falcatum L. roots to be prime candidates for therapeutic strategies towards inflammation.