Background: Ganoderma(Lingzhiin Chinese) has shown good clinical outcomes in the treatment of insomnia, restlessness, and palpitation. However, the mechanism by whichGanodermaameliorates insomnia is unclear. We explored the mechanism of the anti-insomnia effect ofGanodermausing systems pharmacology from the perspective of central-peripheral multi-level interaction network analysis.Methods: The active components and central active components ofGanodermawere obtained from the TCMIP and TCMSP databases, then screened to determine their pharmacokinetic properties. The potential target genes of these components were identified using the Swiss Target Prediction and TCMSP databases. The results were matched with the insomnia target genes obtained from the GeneCards, OMIM, DisGeNET, and TCMIP databases. Overlapping targets were subjected to multi-level interaction network analysis and enrichment analysis using the STRING, Metascape, and BioGPS databases. The networks analysed were protein-protein interaction (PPI), drug-component-target gene, component-target gene-organ, and target gene-extended disease; we also performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.Results: In total, 34 sedative-hypnotic components (including 5 central active components) were identified, corresponding to 51 target genes. Multi-level interaction network analysis and enrichment analysis demonstrated thatGanodermaexerted an anti-insomnia effect via multiple central-peripheral mechanisms simultaneously, mainly by regulating cell apoptosis/survival and cytokine expression through core target genes such as TNF, CASP3, JUN, and HSP90αA1; it also affected immune regulation and apoptosis. Therefore,Ganodermahas potential as an adjuvant therapy for insomnia-related complications.Conclusion: Ganodermaexerts an anti-insomnia effect via complex central-peripheral multi-level interaction networks.

Background: Polygonatum sibiricum (PS), a perennial herbaceous plant belonging to the Liliaceae family, is widely distributed in China and other East Asian countries. PS has been used as food and medicine for thousands of years, and its rhizomes are rich in Polygonatum sibiricum polysaccharides (PSP), which exhibit various bioactivities, yet their structural features and therapeutic mechanisms against ulcerative colitis (UC) remain unclear. Methods: A homogeneous polysaccharide, PSP-1b (57.45 kDa), was isolated from the rhizomes of PS via ion-exchange and gel filtration chromatography and structurally characterized using chromatographic and spectroscopic methods. In vivo, its effects were evaluated in a dextran sulfate sodium (DSS)-induced mouse model of UC, while in vitro mechanisms were explored using macrophages stimulated with lipopolysaccharide (LPS) and neutrophil extracellular traps (NETs). Results: PSP-1b was identified as a neutral polysaccharide with minimal branching. Its primary structural backbone was largely composed of →4)-β-D-Galp-(1→ residues. A portion of these backbone residues was substituted at the O-6 position by side chains primarily composed of β-D-Galp-(1→ units. In vivo, PSP-1b significantly alleviated DSS-induced colitis by reducing inflammatory cytokine secretion, suppressing colonic macrophage infiltration, and reversing neutrophil extracellular traps (NETs) deposition. In vitro, PSP-1b directly interacted with TLR4, inhibited the MAPK/NF-κB signaling pathway, and attenuated LPS- and NET-induced macrophage polarization and inflammation. Conclusions: PSP-1b as a promising candidate for functional foods or therapeutic agents targeting inflammatory bowel disease.