Enhancement of glucose uptake by steroidal alkaloids from Veratrum nigrum

Chemical investigation of the roots and rhizomes of Veratrum nigrum led to the isolation of five new steroidal alkaloids jervine-3-yl formate (1), veramarine-3-yl formate (2), jerv-5,11-diene-3β,13β-diol (3), (1β,3β,5β)-1,3-dihydroxyjervanin-12(13)-en-11-one (4), and veratramine-3-yl acetate (5). Compounds 1 and 5 exhibited potent inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Based on their PTP1B inhibitory activity, the compounds were evaluated for their potential to enhance glucose uptake in C2C12 skeletal muscle cells. The insulin-stimulated glucose uptake was enhanced upon treatment with compounds 1 and 5 (10 µM) by 49.9 ± 6.5% and 56.0 ± 9.7%, respectively. Our results suggest that steroidal alkaloids serve as practical anti-diabetes mellitus leads capable of enhancing glucose uptake.