Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji School of Pharmaceutical Sciences, Huazhong University of Science and Technology, Hangkong Road 13#, Wuhan 430030, China.
Phytomedicine. 2010 Jun;17(7):533-9. doi: 10.1016/j.phymed.2009.10.007. Epub 2009 Dec 3.
In this study, we continued to investigate the hypoglycemic activity of Swertia punicea Helmsl., the hypoglycemic and hypolipidemic effects of methylswertianin and bellidifolin from the active ethyl acetate (EtOAc) fraction, and the potential mechanism(s) underlying the improvement of insulin resistance. Streptozotocin (STZ)-induced type 2 diabetic male BABL/c mice treated with methylswertianin and bellidifolin at different doses (orally, 200 and 100mg/kg body wt./day) for 4 weeks were analyzed in comparison to untreated mice. The results proved that methylswertianin and bellidifolin significantly reduced fasting blood glucose (FBG). The administration of both compounds also improved the oral glucose tolerance and lowered fasting serum insulin (FINS). Moreover, post-administration evaluation revealed lower serum total cholesterol (TC), low density lipoprotein cholesterol (LDL) and triglyceride (TG) levels and increased relative high density lipoprotein cholesterol (HDL) concentrations (HDL/TC). Methylswertianin and bellidifolin appeared to improve insulin resistance by enhancing insulin signaling. The expression levels of insulin-receptor alpha subunit (InsR-alpha), insulin-receptor substrate-1 (IRS-1), and phosphatidylinositol 3-kinase (PI3K) were also increased after administration. Meanwhile, methylswertianin and bellidifolin increased hepatic glycogen content, decreased glucokinase (GK) activities and increased glucose-6-phosphatase (G6Pase) activities. In conclusion, these result indicated that methylswertianin and bellidifolin could be useful for treating type-2 diabetes, likely via the improvement of insulin resistance (IR).
在这项研究中，我们继续研究獐牙菜苦苷的降血糖活性，以及从活性乙酸乙酯（EtOAc）部分中提取的甲基当药宁和bellidifolin 的降血糖和降血脂作用，以及改善胰岛素抵抗的潜在机制。用不同剂量（口服，200 和 100mg/kg 体重/天）的甲基当药宁和bellidifolin 处理 4 周的链脲佐菌素（STZ）诱导的 2 型糖尿病雄性 BABL/c 小鼠，并与未处理的小鼠进行比较。结果证明，甲基当药宁和bellidifolin 显著降低空腹血糖（FBG）。这两种化合物的给药还改善了口服葡萄糖耐量，降低了空腹血清胰岛素（FINS）。此外，给药后的评估显示血清总胆固醇（TC）、低密度脂蛋白胆固醇（LDL）和甘油三酯（TG）水平降低，相对高密度脂蛋白胆固醇（HDL）浓度升高（HDL/TC）。甲基当药宁和bellidifolin 通过增强胰岛素信号来改善胰岛素抵抗。给药后胰岛素受体α亚基（InsR-α）、胰岛素受体底物-1（IRS-1）和磷酸肌醇 3-激酶（PI3K）的表达水平也增加。同时，甲基当药宁和bellidifolin 增加肝糖原含量，降低葡萄糖激酶（GK）活性，增加葡萄糖-6-磷酸酶（G6Pase）活性。总之，这些结果表明，甲基当药宁和bellidifolin 可能对治疗 2 型糖尿病有用，可能是通过改善胰岛素抵抗（IR）。
