麦冬提取物治疗2型糖尿病小鼠的血清代谢组学研究*

目的:采用代谢组学方法研究麦冬对2型糖尿病(T2DM)小鼠内源性代谢物的影响。方法: 腹腔注射链脲佐菌素建立T2DM小鼠模型。连续4周灌胃给予麦冬水提物后,检测血清中糖尿病相关指标,且以超高效液相色谱-飞行时间质谱联用(UPLC-Q/TOF-MS)技术,研究麦冬对T2DM小鼠血清中代谢物质的影响,分析相关代谢通路。结果: 与正常对照组相比,模型组血清的空腹葡萄糖、总胆固醇、甘油三酯、低密度脂蛋白胆固醇含量显著升高,高密度脂蛋白胆固醇含量显著降低;灌胃给予麦冬水提物后,T2DM小鼠血清中以上指标均明显改善。代谢组学结果显示,正常组与模型组共有43个差异代谢物,富集于18条通路;麦冬提取物明显降低T2DM小鼠的甘油酸、丙二酸半醛和4-羟基苯基丙酮酸含量,差异代谢物富集于泛醌和其他萜类醌生物合成代谢等7条通路。结论: 麦冬水提物具有降低T2DM小鼠血糖和血脂的药效作用,且可能与泛醌和其他萜类醌生物合成等通路有关。

Serum Metabolomics of Ophiopogon japonicus Extract Against Type 2 Diabetes in Mice

Objective: To study the protective mechanism of Ophiopogon japonicus extract on Type 2 diabetes mellitus (T2DM) based on metabolomics. Methods: The T2DM mouse model was established by intraperitoneal injection of streptozotocin. Mice were orally administrated with the aqueous extract of Ophiopogon japonicu for 4 weeks. The diabetic phenotypes in serum were measured. Changes in serum metabolites were determined by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). Results: Compared with the control group, the fasting glucose, total cholesterol, triglyceride, and low-density lipoprotein cholesterol were increased in the model group, while the high-density lipoprotein cholesterol decreased significantly, and the above indexes were reversed after treatment of Ophiopogon japonicus extract. The metabonomic results showed that 43 differential metabolites were found between the control group and the model group. These metabolites were enriched in 18 pathways. Ophiopogon japonicus extract significantly decreased the content of glyceric acid, malonic semialdehyde, and 4-hydroxyphenylpyruvic acid in T2DM mice. Ophiopogon japonicus extract could regulate 7 pathways, such as ubiquinone and other terpenoid-quinone biosynthesis. Conclusion: The hypoglycemic and lipid-lowering effect of Ophiopogon on T2DM may be related to ubiquinone and other terpenoid-quinone biosynthesis.