Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Bioorg Med Chem. 2011 May 1;19(9):2835-41. doi: 10.1016/j.bmc.2011.03.040. Epub 2011 Apr 13.
To search for a new class of antidiabetic compounds, effects of 44 flavonoids on the adipogenesis of 3T3-L1 cells were examined. Among them, 3,4',7-trimethylkaempferol, tetramethylkaempferol, and pentamethylquercetin concentration-dependently enhanced the accumulation of triglyceride, a marker of adipogenesis. With regard to structural requirements of flavonoids for the activity, it was fond that: (1) most flavonoids having hydroxy groups lacked the effect; (2) flavonols with methoxy groups showed stronger effects particularly those with a methoxy group at the 3-position; and (3) a methoxy group of flavonols at the B ring was also important. 3,4',7-Trimethylkaempferol, tetramethylkaempferol, and pentamethylquercetin significantly increased the amount of adiponectin released into the medium and the uptake of 2-deoxyglucose into the cells. Furthermore, tetramethylkaempferol and pentamethylquercetin also increased mRNA levels of adiponectin, glucose transporter 4 (GLUT4), and fatty acid-binding protein (aP2). Both compounds also increased the mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ2 and CCAAT/enhancer-binding protein (C/EBP)α, β, and/or δ, although, different from troglitazone, they did not activate PPARγ directly in a nuclear receptor cofactor assay.
为了寻找新型抗糖尿病化合物，研究了 44 种类黄酮对 3T3-L1 细胞脂肪生成的影响。其中，3,4',7-三甲基山奈酚、四甲基山奈酚和五甲基槲皮素浓度依赖性地增强了脂肪生成的标志——甘油三酯的积累。关于类黄酮活性的结构要求，发现：（1）大多数具有羟基的类黄酮缺乏这种作用；（2）具有甲氧基的黄酮醇表现出更强的作用，特别是在 3 位具有甲氧基的黄酮醇；（3）B 环上的黄酮醇的甲氧基也很重要。3,4',7-三甲基山奈酚、四甲基山奈酚和五甲基槲皮素显著增加了细胞培养基中脂联素的释放量和 2-脱氧葡萄糖的摄取量。此外，四甲基山奈酚和五甲基槲皮素还增加了脂联素、葡萄糖转运蛋白 4（GLUT4）和脂肪酸结合蛋白（aP2）的 mRNA 水平。这两种化合物还增加了过氧化物酶体增殖物激活受体（PPAR）γ2 和 CCAAT/增强子结合蛋白（C/EBP）α、β 和/或δ 的 mRNA 水平，尽管与曲格列酮不同，它们在核受体辅因子测定中并没有直接激活 PPARγ。
