Inhibition Mechanism of Mulberry Prenylated Flavonoids Sanggenone D/Kuwanon G Against α-Glucosidase and the Regulation of Glucose via GLUT4 Pathway

文献类型： 外文期刊

第一作者： Wu, Erwen

作者： Wu, Erwen;Zhu, Yanqing;Zou, Yuxiao;Liu, Fan;Li, Qian;Wu, Erwen;Wei, Qingyi;Lu, Huijie;Li, Qian

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关键词： alpha-glucosidase; inhibition mechanisms; molecular docking; Western blotting; structure-activity relationship

期刊名称：NUTRIENTS （ 影响因子：5.0； 五年影响因子：6.0 ）

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年卷期： 2025 年 17 卷 9 期

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收录情况： SCI

摘要： Background: Inhibition of alpha-glucosidase activity is recognized as an effective strategy for managing type 2 diabetes. Methods: The inhibitory mechanisms of two kinds of mulberry flavonoids, namely sanggenone D and kuwanon G, on alpha-glucosidase were investigated and the hypoglycemic pathways were explored in the current study. Results: The outcomes indicate that sanggenone D (IC50: 4.51 x 10-5 mol/L) and kuwanon G (IC50: 3.83 x 10-5 mol/L) inhibited alpha-glucosidase activity by non-competition/anti-competition mixed inhibition and competitive inhibition, respectively. Moreover, the secondary structure of alpha-glucosidase was altered by static quenching and exhibited a decrease in alpha-helix and beta-antiparallel content, and an increase in beta-sheet content. Furthermore, the interaction forces between sanggenone D/kuwanon G and alpha-glucosidase were hydrophobic interactions and hydrogen bonds, as evidenced by molecular docking. The binding affinity, stability, and binding energy aligned with the results of IC50. Notably, the cyclization in sanggenone D structure resulted in a decrease in the number of phenolic hydroxyl groups and thus a reduction in the formation of hydrogen bonds, which ultimately diminished the binding affinity of sanggenone D to alpha-glucosidase. In addition, Western blot analysis further indicated that sanggenone D and kuwanon G regulated glucose metabolism by activating the GLUT4 pathway. Conclusions: The results provided useful reference for the application of sanggenone D and kuwanon G in hypoglycemic functional components.

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