Anti-inflammatory mechanisms of Hedysarum polybotrys polysaccharide in endotoxin-induced uveitis: insights into candidate genes and pathways

To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide (HPS) in a rat model of endotoxin-induced uveitis (EIU).

EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide (LPS, 200 μg) and the rats were then randomly assigned to EIU group (n=5) and the HPS intervention group (n=5). HPS (400 mg/kg, intraperitoneally) or its carrier was administered 24h and 1h prior to EIU induction. Eyes were examined and enucleated 24h post-induction, and total RNA was extracted from the iris-ciliary body. Gene expression microarrays were used to identify differentially expressed genes (DEGs), followed by bioinformatics analyses, including gene ontology (GO) and pathway analysis. Key findings were not experimentally validated at the mRNA or protein level.

A total of 322 DEGs were identified, comprising 254 mRNA and 68 lncRNA genes. GO analysis revealed significant functional categories, including response to LPS. Pathway analysis identified key signaling pathways involved in uveitis, such as cytokine-cytokine receptor interactions. Notably, 16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.

HPS exerts its anti-inflammatory effects through coordinated signaling pathways, offering insights into potential therapeutic targets for managing uveitis.