Anti-Diabetic Effects of Cucurbitacins from Ibervillea lindheimeri on Induced Mouse Diabetes

Abstract

Mexico has a great tradition of using medicinal plants against diabetes. For example, species from the genus Ibervillea traditionally known as “wereque” in Mexican popular medicine have a long ethnobotanical history as anti-diabetic agents. Previous studies by our group indicated that ethyl acetate extract from Ibervillea lindheimeri (I. lindheimeri) roots reduced glucose in mice with chemically induced diabetes. In this work, the primary metabolites of the ethyl acetate extract of I. lindheimeri; 23,24-dihydrocucurbitacin D (1); 2-O-β glucopyranosyl-23,24-dihydrocucurbitacin D (2), and acetylated compounds (3) and (4) obtained from 1 and 2, respectively, were evaluated as anti-hyperglycemic agents in a murine model of chemically induced diabetes. Our results showed that cucurbitacins 1, 2, and 4 reduced glycemia in diabetic CD1 mice compared to the control diabetic group. In addition, the results suggest that compounds 1, 2, and 4 promote glucose transporter type 4 (Glut4) translocation to the plasma membrane (PM) mainly in epididymal adipose tissue (EAT), AMP-activated protein kinase (AMPK) activation in soleus muscle (SM) or dual activation of AMPK, and protein kinase B (AKT) in EAT in an insulin-independent manner when compared to controls. All results together indicate that the isolated cucurbitacins are responsible for the anti-diabetic properties of I. lindheimeri acting predominantly on adipose tissue and call attention to this species as a new source of anti-diabetic compounds.