Exploring the anti-inflammatory targets of Gui-qi-yi-shen granules in diabetic nephropathy: insights from network pharmacology, transcriptomics, and experimental verification
TL;DR
Results indicate that GQYS treats DN mainly through the anti-inflammatory effects, providing a potential theoretical basis for its clinical application and demonstrating the reliability of the integrative strategy.
Abstract
Clinical and animal experiments have shown that Gui-qi-yi-shen (GQYS) granules, a traditional Chinese medicine formula, exhibited considerable therapeutic efficacy in the treatment of diabetic nephropathy (DN). However, the underlying pharmacological mechanisms remain unknown. To address this, we investigated the potential mechanisms of GQYS against DN using an integrated strategy combining network pharmacology and transcriptomics, followed by molecular docking and in vivo validation in db/db mice. A total of 64 unique active compounds and 670 potential targets of GQYS were identified. 213 candidate targets for GQYS-DN were further defined at the intersection of active compound targets of GQYS and disease targets of DN. 53 core targets were identified through network analysis. Integration of network pharmacology with transcriptomics identified 11 hub targets. The enriched signaling pathways mainly focus on inflammatory signaling pathways, including the TNF signaling pathway, IL-17 signaling pathway, and toll-like receptor signaling pathway. Molecular docking and molecular dynamics simulations suggested stable complexes of IL1β-quercetin, Cdkn1a-quercetin, Jun-quercetin, and Jun-β-sitosterol. The docking results, along with in vivo experiments supported the main targets and relevant signaling pathways, thereby demonstrating the reliability of the integrative strategy. Collectively, our results indicate that GQYS treats DN mainly through the anti-inflammatory effects, providing a potential theoretical basis for its clinical application.