Dammarane triterpenoids with anti-inflammatory and promoting glucose uptake activities from the leaves of Cyclocarya paliurus

Abstract

Fourteen triterpenoids, namely eight undescribed dammarane triterpenoid saponins (1–8, named cypaliurusides S–Z₇) and six known analogues (9–14), were isolated from the leaves of Cyclocarya paliurus. The undescribed compounds exhibited diverse side-chain modifications, including conjugated double bonds, multiple hydroxyl groups and a five-member oxygen ring formed via 20,24-diol dehydration. Their structures were elucidated through comprehensive nuclear magnetic resonance (NMR) (1D/2D) and high-resolution electrospray ionisation mass spectrometry data analysis, with absolute configurations determined by dimolybdenum tetraacetate induced circular dichroism spectra and density functional theory gauge-independent atomic orbital ¹³C-NMR calculation. Bioactivity evaluation revealed that cypaliurusides T (2) and U (3) exhibited potent anti-inflammatory activity [half-maximal inhibitory concentration (IC₅₀) = 7.6 and 8.1 μM, respectively], surpassing that of the positive control dexamethasone (IC₅₀ = 9.2 μM). Additionally, cypaliurusides S (1), T (2), U (3), X (5) and Y (6) showed a dose-dependent enhancement of insulin-stimulated glucose uptake in 3T3-L1 adipocytes at concentrations of 2.5–10 μM. Structure–activity relationship analysis indicated that C-24/C-25 dihydroxylation is critical for anti-inflammatory activity, while the C-25 hydroxyl group is essential for enhancing glucose uptake. These findings may contribute to the discovery of antidiabetic agents.