Abstract:

This study investigates the pharmacodynamic material basis of Qizhi Yishen Capsules (QYC) against diabetic kidney disease (DKD) by focusing on the constituents absorbed into blood,integrating network pharmacology and experimental validation.The constituents absorbed into blood of QYC were identified using UPLC-Q-Exactive-Orbitrap MS/MS technology.Key pharmacodynamic compounds and core targets associated with the anti-DKD effects of QYC were screened through network pharmacology.Additionally,molecular docking techniques were employed to analyze the binding affinity between these key pharmacodynamic compounds and their core targets.This study established two models to further validate the activity of the selected pharmacodynamic compounds.The first model was constructed by inducing injury in human renal cortex proximal tubular epithelial cells (HK-2) via high-glucose stimulation,thereby simulating the cytopathological state characteristic of DKD.The second model was established using a combination of a high-fat and high-sugar diet along with streptozotocin to induce a DKD rat model.The key pharmacodynamic compounds were verified by these two models.In conclusion,a total of 23 constituents absorbed into blood were identified in QYC.Network pharmacology was employed to analyze these components.The results revealed that nine key pharmacodynamic components,including rhein,astragaloside Ⅳ,emodin,and catalpol were screened,and five core targets,such as EGFR and HSP90AA1 were identified.The results of the molecular docking between the components and the targets were satisfactory.Subsequent cell and animal experiments demonstrated that these pharmacodynamic components could significantly ameliorate HK-2 cell damage induced by high glucose and improve renal injury in DKD rats.This study elucidated the key pharmacodynamic substances of QYC anti-diabetic nephropathy,laying a foundation for further developing quality standards and clinical application promotion.

Key words:

"> Qizhi Yishen capsules, diabetic kidney disease, UPLC-Q-Exactive-Orbitrap MS/MS, network pharmacology, pharmacodynamic material basis