ArticleFrontiers in molecular biosciences2025
Investigating potential targets of Wulingsan in diabetic nephropathy through network pharmacology and experimental validation.
Article in Frontiers in molecular biosciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Zhuangyang Bushen Pill Attenuates Renal Injury in Chronic Glomerulonephritis by Suppressing the MAPK Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Chemical Profiling and Mechanistic Insights into Stichopodidae Viscus Extract for Ulcerative Colitis via UPLC-IMS-Q-TOF-HDMSPharmaceuticals (Basel, Switzerland) · 2026Article
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3 authors.
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Abstract
Background: Diabetic Nephropathy (DN), a major microvascular complication of diabetes, poses challenges for current treatments to effectively delay its progression. Wulingsan (WLS), a traditional Chinese medicine formula, possesses potential for regulating water-fluid metabolism, and exhibits anti-inflammatory and antioxidant properties, yet its multi-target mechanism in treating DN remains unclear. This study aims to systematically elucidate the molecular mechanisms of WLS in the treatment of DN through network pharmacology, molecular docking, and Methods: Active ingredients of WLS and their targets were screened using the TCMSP database, while DN-related targets were obtained from the GeneCards and OMIM databases to construct an "ingredient-target-disease" network. GO and KEGG pathway enrichment analyses were performed using DAVID to identify key biological processes and signaling pathways. A protein-protein interaction (PPI) network was constructed via the STRING database, and key targets were screened using the CytoHubba plugin. Subsequently, molecular docking and molecular dynamics simulations were conducted to validate the binding affinity and stability of active ingredients with key targets. Results: The study screened and identified SRC, AKT1, TNF, ESR1, and HSP90AA1 as key targets for the treatment of DN. KEGG enrichment analysis revealed that WLS primarily regulates signaling pathways such as PI3K-Akt and MAPK, which are closely associated with inflammation, oxidative stress, and fibrosis. Molecular docking indicated that active ingredients (β-caryophyllene, alisol C) exhibited binding energies below -5.0 kcal/mol with key targets (TNF, HSP90AA1), and molecular dynamics simulations further validated their binding stability. Conclusion: Wulingsan alleviates the progression of Diabetic Nephropathy by its multiple active ingredients acting synergistically on key targets such as SRC, AKT1, and TNF, thereby regulating PI3K-Akt and MAPK signaling pathways to inhibit inflammation, oxidative stress, and fibrosis. This research provides a theoretical basis for the clinical application of WLS, and its therapeutic efficacy warrants further verification through future
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