New dammarane triterpenoid saponins from the leaves of Cyclocarya paliurus
Abstract Three new dammarane triterpenoid saponins, cyclocariosides O-Q (1–3), were isolated from the ethanolic extracts of the leaves of Cyclocarya paliurus. The structures of these compounds were elucidated by spectroscopic methods.
Bioactive dammarane triterpenoid saponins from the leaves of Cyclocarya paliurus.
Thirteen undescribed dammarane triterpenoid saponins (cypaliurusides A-M), including eleven seco-dammarane type triterpenoids, were isolated from Cyclocarya paliurus. Each of these compounds has the unique feature of having a monosaccharide attached to C-11, rather than C-12, compared to the same type of saponins found in this plant. The structures of them were determined by comprehensive analysis of 1D, 2D NMR and HRESIMS data. Cypaliuruside J showed significant α-glucosidase inhibitory effect with IC50 value of 2.22 ± 0.13 μM. In addition, Cypaliurusides F and K exhibited modest cytotoxic activities against selected human cancer cell lines in vitro, with IC50 values ranging from 4.61 ± 0.13 to 15.23 ± 3.88 μM.
Deciphering Molecular Mechanism Underlying Hypolipidemic Activity of Echinocystic Acid
Our previous study showed that a triterpene mixture, consisting of echinocystic acid (EA) and oleanolic acid (OA) at a ratio of 4 : 1, dose-dependently ameliorated the hyperlipidemia and atherosclerosis in rabbits fed with high fat/high cholesterol diets. This study was aimed at exploring the mechanisms underlying antihyperlipidemic effect of EA. Molecular docking simulation of EA was performed using Molegro Virtual Docker (version: 4.3.0) to investigate the potential targets related to lipid metabolism. Based on the molecular docking information, isotope labeling method or spectrophotometry was applied to examine the effect of EA on the activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, acyl-CoA:cholesterol acyltransferase (ACAT), and diacylglycerol acyltransferase (DGAT) in rat liver microsomes. Our results revealed a strong affinity of EA towards ACAT and DGAT in molecular docking analysis, while low binding affinity existed between EA and HMG-CoA reductase as well as between EA and cholesteryl ester transfer protein. Consistent with the results of molecular docking, in vitro enzyme activity assays showed that EA inhibited ACAT and DGAT, with IC50 values of 103 and 139 μM, respectively, and exhibited no significant effect on HMG-CoA reductase activity. The present findings suggest that EA may exert hypolipidemic effect by inhibiting the activity of ACAT and DGAT.