Exploration of the molecular mechanisms of Yishen Qingzhuo oral liquid in regulating lipid metabolism in diabetic Kidney Disease Based on Liquid Chromatography – Mass Spectrometry, Molecular Docking, and Molecular Dynamics Simulation

Abstract

This study investigated the molecular mechanisms by which Yishen Qingzhuo oral liquid regulates lipid metabolism in diabetic kidney disease (DKD) using liquid chromatography–mass spectrometry (LC-MS) combined with network pharmacology, molecular docking, and molecular dynamics simulation. LC-MS, in conjunction with the BATMAN-TCM database, identified 35 active components of the drug and 1275 associated targets. DKD-related targets were screened using the GeneCards and OMIM databases, yielding 2120 targets. Venny 2.1 analysis revealed 325 potential overlapping targets between drug and disease. The potential targets were imported into the STRING database to construct a protein–protein interaction network and identify core targets and components. Gene Ontology enrichment analysis revealed the potential involvement of responses to oxidative stress, regulation of apoptotic processes, fatty acid homeostasis, regulation of autophagy and fatty acid metabolic. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis illustrated that the drug improves DKD by targeting pathways related to lipids and atherosclerosis, apoptosis, autophagy, and fatty acid degradation. Molecular docking revealed strong binding activity between core targets and active components, which was further validated by molecular dynamics simulations, demonstrating stable and tight binding. These findings suggested that Yishen Qingzhuo oral liquid regulates lipid metabolism in DKD through multiple components and targets.