济南大学生物学院张华教授团队在Journal of Agricultural and Food Chemistry发表题目为“Structurally Diverse Stilbenoids as Potent α-Glucosidase Inhibitors with Antidiabetic Effect from Morus alba”研究论文（桑树中结构多样的芪类化合物是具有抗糖尿病作用的强效 α-葡萄糖苷酶抑制剂）。摘要： 从著名的经济作物桑树中分离得到 15 种具有不同骨架的芪类衍生物，包括 5 种以前未描述的衍生物（阿尔巴酚 A–E、1–5）。通过详细解释光谱数据以及核磁共振 (NMR) 和电圆二色性 (ECD) 的量子化学计算分析，充分表征了它们的结构（包括绝对立体化学）。阿尔巴酚 A （1）具有前所未有的重排碳骨架，包含新颖的 2-氧杂螺[双环[3.2.1]辛烷-6,3′-呋喃]基序；阿尔巴酚 C （3）很可能是通过有趣的分子内酯交换反应由共代谢物衍生而来的；阿尔巴酚 E （5）通过二氧杂环己烷环带有裂解-重联支架。所有化合物均对糖尿病靶标 α-葡萄糖苷酶表现出显著抑制作用，IC50 值低至亚微摩尔（0.70–8.27 μM），并通过荧光猝灭、动力学和分子对接实验进一步研究了所选分子与酶的结合模式。在糖尿病小鼠体内进一步评估了活性最高、含量最丰富的桑树呋喃 G (6) 的抗糖尿病作用，结果显示其具有强效的抗高血糖活性，抗糖尿病功效可与临床药物阿卡波糖相媲美。研究结果：Figure 1. Chemical structures of compounds 1–15.3.1. 新的和已知的二苯乙烯类衍生物的鉴定Figure 2. 2D NMR correlations of compounds 1–5.Figure 3. Comparison of the experimental 13C NMR data for 1 (A, B) and 4 (C, D) with the calculated data for their two possible stereoisomers.Figure 4. Experimental and calculated ECD spectra for 1–5 and 11.Figure 5. Comparison of the experimental 13C NMR data for 5 with the calculated data for the four possible stereoisomers.Figure 6. Proposed biosynthetic pathways for compounds 1 and 4.3.2. 生物学评价3.2.2. 荧光猝灭实验Figure 7. Fluorescence emission spectra of α-glucosidase without or with varying concentrations of 1 (A), 3 (B), and 6 (C) (upper graphs) and the corresponding Stern–Volmer plots for the quenching of α-glucosidase in a concentration-dependent manner (lower graphs).3.2.3. 6对α-葡萄糖苷酶的抑制动力学Figure 8. Lineweaver–Burk reciprocal plot (left side) of compound 6 against α-glucosidase, the secondary plot of slope (middle side) and intercept (right side) versus the concentrations of 6.3.2.4. 分子对接分析Figure 9. Binding mode of compound 6 with α-glucosidase from molecular docking. α-Glucosidase and 6 are shown as surface (A) and sticks (B), respectively. (C) Interactions between 6 and α-glucosidase.3.2.5. 评估 6 在正常小鼠中的抗高血糖潜力3.2.6. 6 对糖尿病小鼠的降血糖作用评价3.2.7. 6对糖尿病小鼠治疗效果的评价Figure 10. Compound 6 showed good in vivo antihyperglycemic effect.3.2.8. 6对糖尿病小鼠主要器官的影响3.2.9. 6对糖尿病小鼠生理生化指标的影响Figure 11. Influence of compound 6 on major organs and other physiological indicators of diabetic mice.原文链接：https://doi.org/10.1021/acs.jafc.4c01681
