Failing pancreas and subsequent loss of pancreatic β cells worsen diabetic conditions which are further alleviated by the mounting up of glucose levels. Inhibition of sodium glucose cotransporter 2 (SGLT2) in the kidney responsible for glucose reabsorption strikingly reduces blood glucose levels. Bioactive swertisin showed a promising glucose-lowering effect. Hence, we aimed to mechanistically dissect the glucose lowering property of swertisin. A systematic in silico, in vitro, and in vivo approach was directed for target analysis of swertisin. Molecular docking was performed with Swertisn-hSGLT2 complex. Glucose uptake assay and protein expression for SGLT2 and regulatory proteins were performed under swertisin effect. Various physiological and metabolic parameters were evaluated in STZ induced BALB/c mice using swertisin treatment. SGLT2 expression was evaluated in the kidney tissue of mice. Swertisn-hSGLT2 molecularly docked complex showed similar binding energy compared to the Canagliflozin-hSGLT2 complex. Swertisin inhibited glucose uptake and decreased expression of SGLT2 in HEK293 cells. Swertisin does not affect GLUT mediated glucose transport. Swertisin treated diabetic mice demonstrated remarkable improvement in overall glucose homeostasis. Reduced expression of SGLT2 was found in kidney tissue along with reduced PKC expression which is one of the key regulators of SGLT2. Our study explored SGLT2 as a selective target of swertisin for its swift glucose-lowering action which not only inhibits SGLT2 but also reduces its expression in diabetic condition. Thus, the potential property of swertisin as a glucose-lowering agent is remarkable which points towards the likelihood of a wider avenue of diabetes therapy.

失败的胰腺和随后的胰腺 β 细胞丢失会加重糖尿病病情，而随着血糖水平的升高，这种情况会进一步缓解。抑制肾脏中负责葡萄糖重吸收的钠葡萄糖协同转运蛋白 2 (SGLT2) 可显着降低血糖水平。生物活性 swertisin 显示出有希望的降糖作用。因此，我们旨在从机制上剖析 swertisin 的降糖特性。一个系统的计算机、体外和体内方法是针对swertisin的目标分析。用 Swertisn-hSGLT2 复合物进行分子对接。SGLT2 和调节蛋白的葡萄糖摄取测定和蛋白质表达在 swertisin 作用下进行。使用 swertisin 处理在 STZ 诱导的 BALB/c 小鼠中评估了各种生理和代谢参数。在小鼠的肾组织中评估了 SGLT2 表达。与 Canagliflozin-hSGLT2 复合物相比，Swertisn-hSGLT2 分子对接复合物显示出相似的结合能。Swertisin 抑制葡萄糖摄取并降低 HEK293 细胞中 SGLT2 的表达。Swertisin 不影响 GLUT 介导的葡萄糖转运。Swertisin 治疗的糖尿病小鼠表现出整体葡萄糖稳态的显着改善。在肾组织中发现 SGLT2 表达降低以及 PKC 表达降低，PKC 是 SGLT2 的关键调节因子之一。我们的研究探索了 SGLT2 作为 swertisin 的选择性靶标，因为它具有迅速的降糖作用，不仅可以抑制 SGLT2，还可以降低其在糖尿病条件下的表达。因此，swertisin 作为降糖剂的潜在特性是显着的，这表明可能有更广泛的糖尿病治疗途径。