Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China.
J Pharm Pharmacol. 2017 Oct;69(10):1409-1417. doi: 10.1111/jphp.12778. Epub 2017 Jul 19.
In our previous studies, Dendrobium nobile Lindl. alkaloids (DNLA) has been shown to have glucose-lowering and antihyperlipidaemia effects in diabetic rats, in rats fed with high-fat diets, and in mice challenged with adrenaline. This study aimed to examine the effects of DNLA on the expression of glucose and lipid metabolism genes in livers of mice.
Mice were given DNLA at doses of 10-80 mg/kg, po for 8 days, and livers were removed for total RNA and protein isolation to perform real-time RT-PCR and Western blot analysis.
Dendrobium nobile Lindl. alkaloids increased PGC1α at mRNA and protein levels and increased glucose metabolism gene Glut2 and FoxO1 expression. DNLA also increased the expression of fatty acid β-oxidation genes Acox1 and Cpt1a. The lipid synthesis regulator Srebp1 (sterol regulatory element-binding protein-1) was decreased, while the lipolysis gene ATGL was increased. Interestingly, DNLA increased the expression of antioxidant gene metallothionein-1 and NADPH quinone oxidoreductase-1 (Nqo1) in livers of mice. Western blot on selected proteins confirmed these changes including the increased expression of GLUT4 and PPARα.
DNLA has beneficial effects on liver glucose and lipid metabolism gene expressions, and enhances the Nrf2-antioxidant pathway gene expressions, which could play integrated roles in regulating metabolic disorders.
在我们之前的研究中,已经证实铁皮石斛生物碱(DNLA)在糖尿病大鼠、高脂肪饮食喂养的大鼠和肾上腺素刺激的小鼠中具有降血糖和抗高血脂作用。本研究旨在研究 DNLA 对小鼠肝脏葡萄糖和脂质代谢基因表达的影响。
小鼠给予 DNLA 剂量为 10-80mg/kg,po,连续 8 天,取出肝脏进行总 RNA 和蛋白质分离,进行实时 RT-PCR 和 Western blot 分析。
铁皮石斛生物碱在 mRNA 和蛋白质水平上增加了 PGC1α 的表达,并增加了葡萄糖代谢基因 Glut2 和 FoxO1 的表达。DNLA 还增加了脂肪酸β氧化基因 Acox1 和 Cpt1a 的表达。脂质合成调节剂 Srebp1(固醇调节元件结合蛋白-1)减少,而脂肪分解基因 ATGL 增加。有趣的是,DNLA 增加了小鼠肝脏抗氧化基因金属硫蛋白-1 和 NADPH 醌氧化还原酶-1(Nqo1)的表达。对选定蛋白质的 Western blot 证实了这些变化,包括 GLUT4 和 PPARα 的表达增加。
DNLA 对肝脏葡萄糖和脂质代谢基因表达具有有益的影响,并增强了 Nrf2 抗氧化途径基因的表达,这可能在调节代谢紊乱中发挥综合作用。