Department of Food and Nutrition, Korea University, Seoul 136-703, Republic of Korea.
Food Chem Toxicol. 2013 Jul;57:84-90. doi: 10.1016/j.fct.2013.03.010. Epub 2013 Mar 21.
We aimed to test whether fisetin could modulate cholesterol homeostasis in rats with diet-induced hypercholesterolemia, and further investigated the underlying mechanisms by which fisetin exerts its cholesterol lowering effect. Blood lipid profile, hepatic cholesterol content, as well as gene expressions in cholesterol metabolism were examined. Elevated levels of total cholesterol and LDL-cholesterol, along with hepatic cholesterol content in a high fat group were found to be significantly reduced by fisetin. The high fat diet significantly decreased hepatic mRNA levels of LDLR, SREBP2, HMGCR and PCSK9 in comparison to the control diet, however, fisetin did not further elicit any changes in mRNA levels of the same genes. The high fat diet dramatically increased the transcript levels of CYP7A1, which was subsequently reversed by the fisetin. In HepG2 cells, fisetin was found to increase the levels of a nuclear form of SREBP2 and LDLR. In conclusion, fisetin supplementation displayed hypocholesterolemic effects by modulating the expression of genes associated with cholesterol and bile acid metabolism.
我们旨在测试非瑟酮是否可以调节饮食诱导的高胆固醇血症大鼠的胆固醇稳态，并进一步研究非瑟酮降低胆固醇作用的潜在机制。检测了血脂谱、肝胆固醇含量以及胆固醇代谢相关基因的表达。结果发现，非瑟酮可显著降低高脂肪组大鼠的总胆固醇和 LDL-胆固醇水平以及肝胆固醇含量。与对照饮食相比，高脂肪饮食显著降低了 LDLR、SREBP2、HMGCR 和 PCSK9 的肝 mRNA 水平，但非瑟酮并未进一步改变这些基因的 mRNA 水平。高脂肪饮食显著增加了 CYP7A1 的转录水平，而非瑟酮则逆转了这一现象。在 HepG2 细胞中，非瑟酮被发现增加了核形式的 SREBP2 和 LDLR 的水平。综上所述，非瑟酮通过调节与胆固醇和胆汁酸代谢相关的基因表达，表现出降胆固醇作用。
