Unraveling the Immunomodulatory Mechanisms of Quan-du-zhong Capsule in Diabetic Kidney Disease via Integrated Network Pharmacology and Experimental Validation.

Abstract

Introduction: Quan-du-zhong capsule (QDZ), derived from Eucommia ulmoides Oliv, is clinically utilized for diabetic kidney disease (DKD) management due to its renoprotective effects. Recent studies have demonstrated that QDZ ameliorates proteinuria and attenuates the decline in glomerular filtration rate (GFR) in DKD patients; however, the underlying mechanisms remain unclear.

Methods: To elucidate the active components of QDZ and their potential association with immune cell modulation, we conducted bioinformatics analyses using GEO datasets and CIBERSORT to assess immune cell infiltration. Furthermore, molecular docking experiments and experimental validation were performed to verify the interactions between QDZ and potential immunotherapeutic targets.

Results: Network pharmacology analysis identified the main active components of QDZ, including Quercetin, Kaempferol, β-carotene, β-sitosterol, and Syringetin. Furthermore, bioinformatics and molecular docking studies demonstrated that the FOS gene and the MAPK signaling pathway exhibit differential expression in DKD patients and were significantly correlated with immune cell activity. Notably, the active components-particularly Quercetin, Kaempferol, and Syringetin- displayed strong binding affinities to key targets. In addition, QDZ significantly upregulated FOS and MAPK expression and enhanced glucose uptake in HG-induced HEK-293 cells, suggesting its role in improving insulin sensitivity.

Conclusions: This study illustrates the mechanism by which QDZ upregulates FOS expression and modulates the MAPK signaling pathway, thereby regulating immune cell function in DKD. These findings provide novel insights to inform future research and development of QDZ-based DKD therapies.