| 摘要 |
[Objectives] This study was conducted to explore the mechanisms of active components from Ganoderma lucidum against diabetic tubulopathy based on network pharmacology and molecular docking. [Methods] Small-molecule compounds of G. lucidum were screened from the TCMSP database (OB ≥ 55%, DL ≥ 2), and their targets were predicted via SwissTargetPrediction. Known molecular targets of G. lucidum polysaccharides (GLP) were obtained through literature review, and the two tracks were merged to obtain the drug target set. Disease-related targets of diabetic tubulopathy were retrieved from the GeneCards database (relevance score ≥ 30), and common targets were obtained by intersection with the drug targets. A PPI network was constructed using the STRING platform, and topological analysis was performed with Cytoscape software to screen key targets. GO and KEGG pathway enrichment analyses were conducted. Molecular docking was performed using AutoDock Vina to verify the binding affinity between key components and targets. [Results] A total of 17 active small molecules of G. lucidum were identified (4 steroids and 13 triterpenoids), yielding 168 unique targets. Literature mining of GLP provided 43 targets. The two tracks were merged, resulting in 200 drug targets. Intersection with 10 918 disease targets yielded 184 common targets. The PPI network comprised 182 nodes and 2 317 edges, and 47 hub genes were identified (degree ≥ 36). Among them, IL6, TNF, AKT1 and IL1B showed the highest degree values. hnRNPF exhibited only weak PPI connections with TNF, AKT1, and HIF1A (scores 0.154-0.186), suggesting its involvement in the disease network through post-transcriptional regulation. The AGE-RAGE signaling pathway was the most significantly enriched in the KEGG analysis (24 genes, FDR = 2.18 × 10-23). The results of molecular docking showed that Ganosporelactone B exhibited a binding energy of -10.22 kcal/mol with hnRNPF and of -13.27 kcal/mol with HIF1A, demonstrating a multi-target binding advantage. [Conclusions] The active components of G. lucidum exert anti-diabetic tubulopathy effects through multi-component, multi-target, and multi-pathway mechanisms, and the AGE-RAGE signaling pathway served as a central mechanistic hub. hnRNPF may be directly targeted by G. lucidum triterpenoids and participate in the disease process through post-transcriptional regulation. |
