Poncirin, a natural flavanone glycoside present abundantly in many citrus fruits, contains an extensive range of biological activities. However, the antidiabetic mechanism of poncirin is unexplored yet. In this study, we examined the anti-diabetic prospective of poncirin by evaluating its ability to inhibit protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, human recombinant AR (HRAR), rat lens aldose reductase (RLAR), and advanced glycation end-product (AGE) formation (IC₅₀ = 7.76 ± 0.21, 21.31 ± 1.26, 3.56 ± 0.33, 11.91 ± 0.21, and 3.23 ± 0.09 µM, respectively). Kinetics data and docking studies showed the lowest binding energy and highest affinity for the mixed and competitive type of inhibitors of poncirin. Moreover, the molecular mechanisms underlying the antidiabetic outcomes of poncirin in insulin resistant C2C12 skeletal muscle cells were explored, which significantly increased glucose uptake and decreased the expression of PTP1B in C2C12 cells. Consequently, poncirin increased GLUT-4 expression level by activating the IRS-1/PI3K/Akt/GSK-3 signaling pathway. Moreover, poncirin (0.5–50 µM) remarkably inhibited the formation of fluorescent AGE, nonfluorescent CML, fructosamine, and β-cross amyloid structures in glucose-fructose-induced BSA glycation during 4 weeks of study. Poncirin also notably prevented protein oxidation demonstrated with decreasing the protein carbonyl and the consumption of protein thiol in the dose-dependent manner. The results clearly expressed the promising activity of poncirin for the therapy of diabetes and its related complications.

庞西林是大量存在于许多柑橘类水果中的天然黄烷酮糖苷，具有广泛的生物活性。然而，尚未开发出poncirin的抗糖尿病机制。在这项研究中，我们通过评估其对蛋白酪氨酸磷酸酶1B（PTP1B），α-葡萄糖苷酶，人重组AR（HRAR），大鼠晶状体醛糖还原酶（RLAR）和晚期糖基化末端的抑制能力，研究了poncirin的抗糖尿病前景。产品（AGE）的形成（IC ₅₀ 分别为7.76±0.21、21.31±1.26、3.56±0.33、11.91±0.21和3.23±0.09 µM。动力学数据和对接研究表明，对于混合型和竞争性类型的poncirin抑制剂，结合能最低，亲和力最高。此外，探索了poncirin在胰岛素抵抗性C2C12骨骼肌细胞中抗糖尿病作用的分子机制，该机制显着增加了葡萄糖的摄取并降低了C2C12细胞中PTP1B的表达。因此，poncirin通过激活IRS-1 / PI3K / Akt / GSK-3信号通路提高了GLUT-4表达水平。此外，在4周的研究中，poncirin（0.5–50 µM）显着抑制了葡萄糖-果糖诱导的BSA糖基化过程中荧光AGE，非荧光CML，果糖胺和β-交叉淀粉样蛋白结构的形成。庞西林还显着地防止了蛋白质氧化，这是通过减少蛋白质羰基和减少蛋白质硫醇的剂量依赖性实现的。结果清楚地表明了poncirin在治疗糖尿病及其相关并发症方面的有希望的活性。