Predictive Analysis on the Mechanism of Dendrobium officinale Polysaccharides in Treating Hepatic Fibrosis via Network Pharmacology and Molecular Docking.

OBJECTIVE

The possible anti-liver fibrosis (LF) mechanism of Dendrobium officinale polysaccharides (DOP) has been explored, and the potential core targets of monosaccharides therein have been analyzed through network pharmacology and molecular docking techniques.

METHODS

High-performance anion-exchange chromatography (HPAEC) was performed to determine the monosaccharide components of DOP after extraction. In network pharmacology analysis, the TCMSP, SuperPred, SwissTargetPrediction, and PharmMapper databases (for the potential targets of monosaccharides), as well as the GeneCards and OMIM databases (for potential targets of LF), were used to predict the potential targets through which monosaccharides may reverse LF. The STRING database was used to construct a protein-protein interaction (PPI) network, which was visualized using the Cytoscape application. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for functional annotation and pathway analysis, respectively. In molecular docking, the AutoDock Vina application was used to predict the mechanism of major monosaccharides against LF.

RESULTS

The extracted DOP contains seven main monosaccharides: glucose (Glu), mannose (Man), xylose (Xyl), galactose (Gal), arabinose (Ara), galacturonic acid (Gal-UA), and rhamnose (Rha). The network pharmacology analysis revealed 15 core targets of DOP monosaccharides against LF. Functional annotation of 427 overlapping targets revealed primary enrichment in cell proliferation, inflammatory response, hypoxia and oxidoreductase activity, extracellular matrix disassembly, abnormal lipid metabolism and peroxidation, ERK1/2 cascade reaction, mitochondrion and ATP binding, and other aspects. At the same time, the signaling pathways involved in these targets are enriched in VEGF, EGFR, HIF-1, FoxO, MAPK, PI3K-Akt-mTOR, AMPK, JAK-STAT, NF-κB, apoptosis, and other pathways. Molecular docking demonstrated that several key-including MAPK3, MMP9, ALB, HSP90αB1, SRC, and NFKB1-exhibited good binding affinities.

CONCLUSION

DOP may exert anti-LF effects by affecting EGFR, STAT1, NF-κB, and MAPK pathways to regulate HSC activation, oxidative stress, lipid peroxidation, ferroptosis, and ECM deposition.