Objective To explore the potential active components and mechanism of Polygonatum sibiricum polysaccharide in the treatment of alcohol-related liver disease (ALD) using network pharmacology and molecular docking technology.

Methods The repeating structural units of Polygonatum sibiricum polysaccharide were obtained through literature review and were drawn using KingDraw 3.0.2.20 software. The potential targets of these structural units were predicted using PharmMapper, SEA, SwissTargetPrediction and Super-PRED databases. Potential therapeutic targets for ALD were identified through GeneCards, OMIM, DrugBank and TTD databases. The "structural unit- disease - target" relationship network and protein-protein interaction (PPI) network of Polygonatum sibiricum polysaccharide were constructed using Cytoscape 3.8.0 software, and the core structural units and key targets of Polygonatum sibiricum polysaccharide with therapeutic effects were screened. Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DAVID database, and molecular docking verification was conducted between the core structural units of Polygonatum sibiricum polysaccharide and key targets.

Results 14 pieces of information on Polygonatum sibiricum polysaccharide structural units were obtained, including 7 linear structural units and 7 branched structural structures. The corresponding targets of Polygonatum sibiricum polysaccharide were 589, ALD-related targets were 2 879, and intersection targets of Polygonatum sibiricum polysaccharide and ALD were 271. The core structural units of Polygonatum sibiricum polysaccharide for the treatment of ALD were MOL3, MOL10, MOL1, MOL5, MOL11, MOL7 and MOL8 with branched structures, and the mechanism mainly involved key targets such as MTOR, CASP3, ALB, STAT3, AKT1, NFKB1 and HIF1A. The results of GO and KEGG analysis indicated that these key targets mainly exert therapeutic effects by regulating signaling pathways such as HIF-1, PI3K-Akt, Ras, and AGE-RAGE in diabetes complications. The molecular docking results showed that MOL3, MOL10, MOL1, MOL5, MOL11, MOL7 and MOL8 all had good affinities for the 7 key targets.

Conclusion Polygonatum sibiricum polysaccharide exerts therapeutic effects on ALD by regulating multiple targets and multiple pathways, providing a reference for in-depth exploration of the core active structure and molecular mechanism of Polygonatum sibiricum polysaccharide in the treatment of ALD.

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