Zhang Wenjie, Zhang Yongxiang, Lv Wenshan, Kong Zili, Wang Fang, Wang Yangang
Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, China; Qingdao Key Laboratory of Thyroid Diseases, Medical Research Cente, Qingdao, China.
Department of Rehabilitation Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.
Biochem Biophys Res Commun. 2025 Jan;744:151142. doi: 10.1016/j.bbrc.2024.151142. Epub 2024 Dec 6.
Diabetic nephropathy (DN) is one of the most severe kidney complications and the primary contributor to end-stage renal disease on a global scale. It exacerbates the morbidity, mortality, and financial burden for individuals with diabetes. Isoquercitrin, a natural compound found in various plants, has demonstrated potential as an antidiabetic agent. However, it remains uncertain whether isoquercitrin exerts a protective effect on DN. Therefore, the objective of this study was to explore whether isoquercitrin confers a protective effect on DN and its potential mechanism. In vivo, a mouse model of DN induced by streptozotocin was established in the study. The hypoglycemic effect of isoquercitrin was assessed by measuring fasting blood glucose levels, insulin tolerance tests, and glucose tolerance test in animals. Urinary albumin creatinine ratio, serum lipid levels, and pathological changes in renal tissues were measured to evaluate the protective effect of isoquercitrin against DN. The expression of Sodium glucose co-transporter-2(SGLT2) was analyzed using real-time quantitative PCR and immunohistochemistry. The studies suggest that isoquercitrin significantly reduces fasting blood glucose levels, enhances the body's capacity to regulate blood glucose and insulin resistance, and facilitates renal pathology and renal function. Simultaneously, it can lower blood lipids (total cholesterol and triglyceride) and improve the risk factors of DN. Meanwhile, isoquercitrin suppressed the expression of SGLT2 in renal tissues of DN mouse models. In vitro, real-time quantitative PCR and Western blot were used to detect the expression of SGLT2 in the human renal tubular epithelial (HK-2) cells. The effects of isoquercitrin on the survival rate and glucose uptake capacity of HK-2 cells were determined by Cell-Counting-Kit-8 and glucose uptake methods. The results demonstrate that isoquercitrin suppressed the up-regulation of SGLT2 mRNA and protein in high-glucose-induced HK-2 cells. Additionally, isoquercitrin inhibited glucose uptake in HK-2 cells and mitigated high-sugar-induced damage. Thus, this study has concluded that isoquercitrin exhibits hypoglycemic and renal protective effects by inhibiting the SGLT2 pathway, indicating its potential as a promising anti-DN drug deserving further clinical investigation.
糖尿病肾病（DN）是最严重的肾脏并发症之一，也是全球范围内终末期肾病的主要病因。它加剧了糖尿病患者的发病率、死亡率和经济负担。异槲皮苷是一种存在于多种植物中的天然化合物，已显示出作为抗糖尿病药物的潜力。然而，异槲皮苷是否对DN具有保护作用仍不确定。因此，本研究的目的是探讨异槲皮苷是否对DN具有保护作用及其潜在机制。在体内实验中，本研究建立了链脲佐菌素诱导的DN小鼠模型。通过测量动物的空腹血糖水平、胰岛素耐量试验和葡萄糖耐量试验来评估异槲皮苷的降血糖作用。测量尿白蛋白肌酐比值、血脂水平和肾组织病理变化，以评估异槲皮苷对DN的保护作用。使用实时定量PCR和免疫组织化学分析钠-葡萄糖协同转运蛋白2（SGLT2）的表达。研究表明，异槲皮苷可显著降低空腹血糖水平，增强机体调节血糖和胰岛素抵抗的能力，并改善肾脏病理和肾功能。同时，它可以降低血脂（总胆固醇和甘油三酯），改善DN的危险因素。此外，异槲皮苷抑制了DN小鼠模型肾组织中SGLT2的表达。在体外实验中，使用实时定量PCR和蛋白质印迹法检测人肾小管上皮（HK-2）细胞中SGLT2的表达。通过细胞计数试剂盒-8和葡萄糖摄取方法测定异槲皮苷对HK-2细胞存活率和葡萄糖摄取能力的影响。结果表明，异槲皮苷抑制了高糖诱导的HK-2细胞中SGLT2 mRNA和蛋白的上调。此外，异槲皮苷抑制HK-2细胞对葡萄糖的摄取，并减轻高糖诱导的损伤。因此，本研究得出结论，异槲皮苷通过抑制SGLT2途径发挥降血糖和肾脏保护作用，表明其作为一种有前景的抗DN药物具有进一步临床研究的潜力。
