Department of Chemical Engineering, Biotechnology and Environmental Technology, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark.
Food Funct. 2015 Jul;6(7):2135-44. doi: 10.1039/c5fo00223k.
A dichloromethane (DCM) extract of carrot roots was found to stimulate insulin-dependent glucose uptake (GU) in adipocytes in a dose dependent manner. Bioassay-guided fractionation of the DCM extract resulted in the isolation of the polyacetylenes falcarinol and falcarindiol. Both polyacetylenes were able to significantly stimulate basal and/or insulin-dependent GU in 3T3-L1 adipocytes and porcine myotube cell cultures in a dose-dependent manner. Falcarindiol increased peroxisome proliferator-activated receptor (PPAR)γ-mediated transactivation significantly at concentrations of 3, 10 and 30 μM, while PPARγ-mediated transactivation by falcarinol was only observed at 10 μM. Docking studies accordingly indicated that falcarindiol binds to the ligand binding domain of PPARγ with higher affinity than falcarinol and that both polyacetylenes exhibit characteristics of PPARγ partial agonists. Falcarinol was shown to inhibit adipocyte differentiation as evident by gene expression studies and Oil Red O staining, whereas falcarindiol did not inhibit adipocyte differentiation, which indicates that these polyacetylenes have distinct modes of action. The results of the present study suggest that falcarinol and falcarindiol may represent scaffolds for novel partial PPARγ agonists with possible antidiabetic properties.
胡萝卜根的二氯甲烷（DCM）提取物被发现以剂量依赖的方式刺激脂肪细胞中胰岛素依赖性葡萄糖摄取（GU）。DCM 提取物的基于生物测定的馏分分离得到多炔化合物 falcarinol 和 falcarindiol。这两种多炔化合物都能够以剂量依赖的方式显著刺激 3T3-L1 脂肪细胞和猪肌管细胞培养物中的基础和/或胰岛素依赖性 GU。Falcarindiol 在 3、10 和 30 μM 的浓度下显著增加过氧化物酶体增殖物激活受体（PPAR）γ 介导的转录激活，而 falcarinol 仅在 10 μM 时观察到 PPARγ 介导的转录激活。对接研究表明，falcarindiol 与 PPARγ 的配体结合域的结合亲和力高于 falcarinol，并且这两种多炔化合物都表现出 PPARγ 部分激动剂的特征。基因表达研究和油红 O 染色表明，falcarinol 可抑制脂肪细胞分化，而 falcarindiol 不抑制脂肪细胞分化，这表明这些多炔化合物具有不同的作用模式。本研究的结果表明，falcarinol 和 falcarindiol 可能代表具有潜在抗糖尿病特性的新型部分 PPARγ 激动剂的支架。
