Constituents of the stem of Cucurbita moschata exhibit antidiabetic activities through multiple mechanisms

Pumpkin has been suggested to have an antidiabetic effect, but the bioactives involved and molecular mechanisms mediating its hypoglycaemic activity are not clear. This study characterized some of the hypoglycaemic constituents in the crude extract of the Cucurbita moschata stem and investigated the mechanisms of their action. The C. moschata stem extract showed a hypoglycaemic effect in vivo in streptozotocin-induced diabetic mice. Several hypoglycaemic fractions of the extract were identified via cell-based screening, and two of them were confirmed to have hypoglycaemic activities in vivo. Ten compounds were afforded from the 2 fractions. Compounds 9 [(22E,24R)-24-methyl-6β-methoxy-5α-cholesta-7,22-diene-3β,5-diol] and 10 [3β-hydroxy-(22E,24R)-ergosta-5,8,22-trien-7-one] showed an insulin-like activity in normal cells that may be mediated by AMP-activated protein kinase. Compounds 4 (ferulic acid), 8 (syringaresinol) and 9 exhibited an insulin sensitizing and/or insulin substitution function in insulin-resistant cells. Thus, the C. moschata stem contains compounds with potential for managing type 1 or type 2 diabetes.