Fenugreek is a well-known medicinal plant used for treatment of diabetes. In this study, the antidiabetic effect of fenugreek flavonoids was investigated by metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Fenugreek flavonoids were purified using polyamide resin and D101 macroporous adsorption resin, characterized by UPLC-Q-TOF-MS, and administered to streptozotocin (STZ)-induced diabetic rats for 28 days. Pharmacological study results indicated that fenugreek flavonoids exerted a strong antidiabetic effect characterized by significant reduction of fasting blood glucose (P < 0.01), increase in serum insulin level (P < 0.01) and liver glycogen content (P < 0.01), attenuation of weight loss, and improvement of pancreatic islet and kidney conditions. The antidiabetic effect of fenugreek flavonoids was further analyzed by metabonomics. Serum samples of health and diabetic rats treated or not with fenugreek flavonoids were evaluated by UPLC-Q-TOF-MS, followed by principal component analysis (PCA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA). The PCA model revealed significant differences among the animal groups, and OPLS-DA identified fenugreek flavonoids-induced changes of 11 potential biomarkers involved in lipid metabolism (docosahexaenoic acid, arachidonic acid, sphinganine, sphingosine‑1‑phosphate, and lysophosphatidylcholines 20:4, 18:2, 16:0, and 20:2), amino acid metabolism (hippuric acid and tryptophan), and kidney function-related metabolism (2‑phenylethanol glucuronide). Our study demonstrates that flavonoids are bioactive components of fenugreek with potent antidiabetic activity, which exert their therapeutic effects by multiple mechanisms, including reducing insulin resistance, improving gluconeogenesis, and protecting islet cells and kidneys from damage.

胡芦巴是一种著名的药用植物，用于治疗糖尿病。在这项研究中，胡芦巴类黄酮的抗糖尿病作用是通过基于超高效液相色谱和四极杆飞行时间质谱（UPLC-Q-TOF-MS）的代谢组学研究的。使用聚酰胺树脂和D101大孔吸附树脂纯化葫芦巴类黄酮，以UPLC-Q-TOF-MS为特征，并对链脲佐菌素（STZ）诱导的糖尿病大鼠给药28天。药理研究结果表明，胡芦巴黄酮具有较强的抗糖尿病作用，其特征是空腹血糖明显降低（P  <0.01），血清胰岛素水平升高（P  <0.01）和肝糖原含量（P <0.01），减轻体重减轻，改善胰岛和肾脏疾病。胡芦巴类黄酮的抗糖尿病作用通过代谢组学进一步分析。通过UPLC-Q-TOF-MS对健康和糖尿病大鼠的血清样品进行了处理，方法是用UPLC-Q-TOF-MS进行评估，然后进行主成分分析（PCA）和正交投影到潜在结构的平方判别分析（OPLS-DA）。PCA模型揭示了动物组之间的显着差异，OPLS-DA确定了胡芦巴类黄酮诱导的11种潜在的与脂质代谢有关的生物标记物的变化（二十二碳六烯酸，花生四烯酸，鞘氨醇，鞘氨醇-1-磷酸和溶血磷脂酰胆碱20：4， 18：2、16：0和20：2），氨基酸代谢（马尿酸和色氨酸），与肾脏功能有关的新陈代谢（2-苯乙醇葡糖醛酸）。我们的研究表明，类黄酮是胡芦巴具有抗糖尿病活性的生物活性成分，它们通过多种机制发挥治疗作用，包括降低胰岛素抵抗，改善糖异生和保护胰岛细胞和肾脏免受损害。