Diosgenin, the Main Aglycon of Fenugreek, Inhibits LXRα Activity in HepG2 Cells and Decreases Plasma and Hepatic Triglycerides in Obese Diabetic Mice
Diosgenin, the Main Aglycon of Fenugreek, Inhibits LXRα Activity in HepG2 Cells and Decreases Plasma and Hepatic Triglycerides in Obese Diabetic Mice
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DOI：
10.3945/jn.110.125591
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发表时间：
2011-01-01
影响因子：
4.2
通讯作者：
Kawada, Teruo
中科院分区：
文献类型：
--
作者：
Uemura, Taku;Goto, Tsuyoshi;Kawada, Teruo
胡芦巴具有改善血脂紊乱的作用，但具体作用机制尚不清楚。在这项研究中，我们研究了胡芦巴对糖尿病肥胖KK-Ay小鼠肝脏脂质代谢的影响，特别是脂肪生成，这在肥胖和糖尿病中得到加强。KK-Ay小鼠饲喂高脂饲料(HFD，60%能量为脂肪)(C组)或含0.5%和2%胡芦巴的高脂饲料(0.5F和2.0F组)4wk。在4wk时，2.0F组大鼠肝脏和血浆中成脂基因的TG和mRNA表达水平均低于C组(P<；0.05)，而0.5F组大鼠肝脏和血浆中的成脂基因表达水平与C组无明显差异。胡芦巴中总皂苷的水解组分，而不是总皂苷组分本身，能抑制细胞内TG的积累。用高效液相色谱法将水解液中的皂苷分离成15个组分，并检测了这些组分对人肝癌细胞系HepG2细胞中甘油三酯积累的影响。组分11抑制甘油三酯在肝癌细胞中的积聚，我们用高效液相色谱-串联质谱法测定了组分11的活性物质S薯蓣皂苷元。薯蓣皂苷元(5和10mU/L)可抑制细胞内甘油三酯的积聚和成脂基因的表达。此外，通过荧光素酶检测系统和凝胶迁移率改变分析，薯蓣皂苷元抑制了肝X受体α的反式激活。这些结果表明，胡芦巴通过降低糖尿病小鼠的肝脏脂质含量来改善血脂异常，其作用是通过薯蓣皂苷元介导的。胡芦巴含有薯蓣皂苷元，可能对治疗糖尿病相关的肝脏血脂紊乱有用。J.Nutr.141：17-23,2011。
Trigonella foenum-graecum (fenugreek) can ameliorate dyslipidemia, but the detailed mechanism is unclear. In this study, we examined the effects of fenugreek on hepatic lipid metabolism, particularly lipogenesis, which is enhanced in obesity and diabetes, in diabetic obese KK-Ay mice. KK-Ay mice were fed a control high-fat diet (HFD; 60% of energy as fat) (C group) or an HFD containing 0.5% or 2% fenugreek (0.5F and 2.0F groups, respectively) for 4 wk. Hepatic and plasma TG and mRNA expression levels of lipogenic genes were lower in the 2.0F group at 4 wk (P < 0.05), but not in the 0.5F group, than in the C group. The hydrolyzed saponin fraction, but not the saponin fraction per se, in fenugreek inhibited the accumulation of TG in HepG2 cells. We fractionated the hydrolyzed saponin into 15 fractions by HPLC and examined the effect of these fractions on TG accumulation in HepG2 cells. Fraction 11 inhibited TG accumulation in HepG2 cells and we determined by liquid chromatography tandem MS that the active substance contained in fraction 11 s diosgenin. Diosgenin (5 and 10 mu mol/L) inhibited the accumulation of TG and the expression of lipogenic genes in HepG2 cells. Moreover, diosgenin inhibited the transactivation of liver-X-receptor-alpha, as measured using a luciferase assay system and by gel mobility shift assay. These findings suggest that fenugreek ameliorates dyslipidemia by decreasing the hepatic lipid content in diabetic mice and that its effect is mediated by diosgenin. Fenugreek, which contains diosgenin, may be useful for the management of diabetes-related hepatic dyslipidemias. J. Nutr. 141: 17-23, 2011.