Pentacyclic Triterpenes from the resin of Liquidambar formosana have anti-angiogenic properties

Abstract

Phytochemical investigation of the resin of Liquidambar formosana Hanc led to the separation and identification of five undescribed pentacyclic triterpenoids, including two lupane type, one taraxerane type, and two oleanane type triterpenoids, in addition to ten known analogues. Structures and relative or absolute configurations were elucidated by intensive spectroscopic methods, and single-crystal X-ray diffraction analysis. All isolated compounds were evaluated for their anti-angiogenic effects in vitro against VEGF-induced endothelial cell proliferation and migration in HUVECs. Among them, (5R, 8R, 9R, 10R, 13S, 14R, 17R, 18R, 19S)-17,18-epoxy-17,18-seco-28-norlupa-17- hydroxy-20 (29) -ene-3-one, (5R, 8R, 9R, 10R, 13S, 14R, 17S, 18S, 19S, 20S)-17, 20-peroxy-28- norlupa -29 -hydroxy- 3-one, 11α,12α:13β,28-diepoxyoleanane- 3-one, 28-norlup-20 (29)-ene- 3β,17β-diol, liquidambaric lactone and 13,28-epoxy-11- oleanene- 3-one significantly inhibited VEGF-induced HUVECs proliferation with IC₅₀ values ranging from 1.64 ± 0.36 to 7.06 ± 0.28 μM. In addition, they also effectively decreased VEGF-induced cell migration with IC₅₀ values ranging from 1.57 ± 0.60 to 4.77 ± 0.62 μM. The structure-activity relationship of these compounds is discussed. The anti-angiogenic property of (5R, 8R, 9R, 10R, 13S, 14R, 17R, 18R, 19S)-17,18-epoxy-17,18-seco-28-norlupa-17- hydroxy-20 (29) -ene-3-one is mediated by the VEGFR2 - AKT signaling pathway.

Keywords: Altingiaceae; Anti-angiogenic effect; Liquidambar formosana Hance; Pentacyclic triterpene.