Integrated network pharmacology and gut microbiota analysis to reveal the immunomodulatory mechanisms of Lonicerae Japonicae Flos polysaccharides

Cyclophosphamide (CTX) is a common anticancer drug that can cause immunosuppression and disrupt the intestinal microbiota when taken long-term or at high doses. Lonicerae Japonicae Flos polysaccharides (LJFP), identified as the principal bioactive constituents of L. Japonicae Flos, have emerged as promising immunomodulatory agents. Herein, we explored the molecular mechanisms through which LJFP alleviate CTX-induced immunosuppression in mice. As determined via gas chromatography (GC), LJFP contain arabinose, rhamnose, ribose, xylose, mannose, fructose, galactose, and glucose. LJFP mitigated the decline in body weight and immune organ indexes in CTX-induced mice, while promoting cytokine production. Moreover, LJFP stimulated immunity by reshaping the gut microbiota of mice, where Muribaculaceae and Alistipes played key roles. LJFP also increased short-chain fatty acid (SCFA) levels in the mouse colon and feces. Network pharmacology analyses identified 31 core targets and relevant signaling pathways implicated in the treatment of immunosuppression. Molecular docking indicated strong binding of the eight monosaccharide components to key targets EGFR, HSP90AA1, and IL2. Notably, fifteen of these targets specific to the gut further suggested that the mechanism through which LJFP ameliorates immunosuppression is intricately linked to the gut microbiota. The current findings highlight the potential of LJFP as a functional food or alternative therapeutic against immunosuppression.