Analysis of potential targets of 20S-protopanaxadiol on diabetic nephropathy based on network pharmacology, molecular docking, and experimental validation

Purpose: This study aims to investigate the protective effects and mechanisms of 20S-protopanaxadiol (PPD), a key component derived from ginseng folium, against diabetic nephropathy (DN).

Methods: Ingredients of ginseng folium were collected and screened using the TCMSP database. Therapeutic target genes for ginseng folium against DN were obtained, and protein-protein interaction (PPI) networks were constructed. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments were conducted on these targets. Furthermore, the results of network pharmacology were validated via molecular docking. Subsequently,the effects of PPD on TGF-β1/Smads signaling pathway were assessed in db/db mice and HK-2 cells using biochemical assays and Western blotting.

Results: A total of 246 target genes for ginseng folium against DN were identified. KEGG analysis revealed significant enrichment in AGE-RAGE signaling in diabetic complications, PI3K-AKT, MAPK, and TNF pathways. PPD intragastric administration improved renal function in db/db mice and significantly reduced the expression of TGF-β1, α-SMA, p-Smad3, and SMAD4 in renal tissue (p < 0.05). Furthermore, PPD decreased the expression of TGF-β1, p-Smad3, and SMAD4 in high glucose-induced HK-2 cells.

Conclusion: PPD potentially alleviates renal fibrosis in db/db mice and HK-2 cells by inhibiting the TGF-β1/Smads pathway, thereby delaying DN progression.

Ginseng folium; TGF-β1/Smads signaling pathway; diabetic nephropathy; network pharmacology; renal fibrosis.