Anti-adipogenic 18,19-seco-ursane stereoisomers and oleane-type saponins from Ilex cornuta leaves

Abstract

Three undescribed seco-ursane stereoisomers, ilexcornutosides A–C, two undescribed triterpenoid saponins, ilexcornutosides D–E, and 11 known triterpenoids were isolated from the leaves of Ilex cornuta Lindl. & Paxton. Ilexcornutosides A–C and F with the same planar structures are unique 13(18)-ene-18,19-seco-ursane skeleton triterpenoids, identified as (3S,12R)-3-O-[β-d-glucopyranosyl-(1 → 2)-α-l-arabinopyranosyl]-12-hydroxyl-19-oxo-18,19-secours-13(18)-en-28,21-lactone. Among them, ilexcornutosides A and F (or ilexcornutosides B and C) are a pair of diastereomers at the C-20 position; ilexcornutosides A and C (or ilexcornutosides B and F) are a pair of diastereomers with epimerization at the C-21. Their structures were established by extensive spectroscopic (IR, 1D and 2D NMR, and HR-ESI-MS) and chemical analyses. The absolute configurations of ilexcornutosides A, B, D and F were determined by a single crystal X-ray diffraction analysis with a Cu Kα radiation. The inhibitory effect of ilexcornutosides A–F on the PPARγ expression was assessed in the 3T3-L1-Lenti-PPARγ-Luc cells using a single luciferase reporter assay. Ilexcornutosides A and C showed a comparable activity in decrease of the PPARγ expression to the positive control (T0070907) at 5 μM.