Polyacetylenes from carrots with potential anti-diabetic effects

In our continuous search for bioactive compounds with anti-diabetic effects, plant extracts were tested in a screening platform consisting of a series of bioassays: PPARγ transactivation, adipocyte differentiation, and glucose uptake. One promising extract was the dichloromethane extract of carrots (Daucus carota) that significantly activated PPARγ with a fold activation of 11.6% at 100mg/mL compared to the vehicle (DMSO) with no or little effect on adipocyte differentiation and stimulated insulin-dependent glucose uptake. Carrots contain highly bioactive aliphatic polyacetylenes, which are also present in related vegetables of the Apiaceae family. These polyacetylenes are very similar in chemical structure to endogenous ligands for PPARγ and hence, may have important PPARγ activating properties. A bioassay-guided fractionation of the extract yielded several polyacetylene-rich fractions, which were all tested in the screening platform and found to be active. Individual polyacetylenes from the active fractions were isolated by a combination of flash CC and semi-preparative HPLC, and characterized by LC-PDA-APCI-MS/MS and NMR spectroscopy. The most bioactive polyacetylenes were falcarinol and falcarindiol, which were able to explain most of the observed bioactivity of the carrot extract.