Effects of Rehmanniae Radix Praeparata polysaccharides on LPS-induced immune activation in mice based on gut microbiota, metabolomics and transcriptomics.

This study explored the immunomodulatory effects of Rehmanniae Radix Praeparata polysaccharides (RP) on LPS-induced immune activation. RP, characterized as a heteropolysaccharide (6.34 kDa and 4.63 kDa) rich in galactose and glucose, was administered to LPS-challenged BALB/c mice at 25 mg/kg and 50 mg/kg doses. Results showed RP significantly reduced pro-inflammatory cytokines (TNF-α, IL-6), lowered oxidative stress (MDA), and boosted antioxidant enzymes (SOD, GSH-Px). It restored splenic structure, mitigated apoptosis, and suppressed the TNF-α/NF-κB/IL-6 pathway. Metabolomics linked RP to sphingolipid metabolism, while gut microbiota analysis revealed increased beneficial bacteria and elevated SCFAs. Transcriptomics confirmed RP's immune regulation via TNF signaling. These findings demonstrate RP's potential in alleviating immune overactivation by modulating inflammation, gut microbiota, and SCFA production, suggesting therapeutic promise for immune-related diseases.