Polysaccharides from Psoralea corylifolia alleviate CTX-induced immunosuppression in mice by modulating gut microbiota- metabolite-immune signaling.

INTRODUCTION

Although polysaccharides from Psoralea corylifolia L. (PPs) have been reported to possess immune-stimulatory effects, their precise mechanisms of action remain unclear.

METHODS

In this study, the potential mechanism of PPs in alleviating CTX-induced immunosuppression was investigated by analyzing the gut microbiota, metabolomics, and immune parameters in mice.

RESULTS

The results showed that PPs significantly alleviated CTX-induced immunosuppression, as evidenced by increased immune organ indices, improved intestinal mucosalintegrity, elevated serum levels of IL-6 and TNF-α, enhanced activities of ACP, LDH, SOD, and GSH-Px, and reduced MDA content. Western blot analysis indicated that PPs activated the NF-kB and MAPK signaling pathways and upregulated the expression of intestinal tight junction proteins (Claudin-1, Occludin, and ZO-1). Immunohistochemical results further revealed that PPs modulated the numbers of CD4+ and CD8+ T cells in the small intestine. Based on 16S rDNA sequencing and untargeted metabolomics analysis, PPs promoted the proliferation of Lachnospiraceae_NK4A136_group and Lactobacillus, while reducing the abundance of Prevotellaceae_UCG-001, f:Lachnospiraceae_Unclassified, and Alloprevotella, thereby ameliorating metabolic disorders and counteracting CTX-induced immunosuppression. Spearman's correlation coefficient analysis indicated significant associations among gut microbiota, serum metabolites, and immune as well as antioxidant indicators.

DISCUSSION: These results suggested that PPs enhanced the immune response in immunocompromised mice by boosting antioxidant capacity, improving the intestinal barrier, modulating gut microbiota structure, and correcting metabolic disturbances.