Inhibition of 11β-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-3β,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 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), with IC 50 values of 34.86 nM, 1.115 μ M, 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 h11β-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. © 2012 by the authors; licensee MDPI, Basel, Switzerland.