Inhibition of 11b-HSD1 by Tetracyclic Triterpenoids from Euphorbia kansui

Abstract

The roots of Euphorbia kansui are considered an important traditional folk medicine. In this study the ethanol extracts of E. kansui were investigated. A new tetracyclic triterpenoid, euphane-3b,20-dihydroxy-24-ene, in addition to five known triterpenoids with euphane skeletons were isolated. Their structures were elucidated on the basis of physical and spectral techniques (1D-, 2D-NMR and MS, respectively). Furthermore, these compounds 1–6 exhibited strong inhibitory activity against human 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1), with IC50 values of 34.86 nM, 1.115 mM, 16.08 nM, 2.815 nM, 26.47 nM, 15.99 nM, and 41.86 nM, respectively. The docking results show that the ring part of compounds can insert into the hydrophobic core of h11b-HSD1 and the alkane chain orientates toward the outside. The results presented herein provide a scientific explanation for the usage of the E. kansui in clinical treatment of diabetes.

Keywords

• tetracyclic triterpenoids
• Euphorbia kansui
• inhibition of 11b-HSD1
• docking