Astragalus Polysaccharides Alleviate Sepsis by Boosting Adrenal Hormone Synthesis and Repairing Microvascular Damage

Sepsis is a severe infection-related condition commonly seen in clinical practice, characterized by systemic inflammation and multi-organ dysfunction. Astragalus polysaccharides (APS), the primary bioactive compound from the traditional Chinese herb Astragalus, has shown significant anti-inflammatory, immunomodulatory, and antioxidant effects. This study aimed to explore APS's potential in alleviating sepsis by enhancing adrenal cortical hormone production and repairing adrenal microvascular damage, while uncovering the underlying molecular mechanisms. Using an SD rat model, sepsis was induced via cecal ligation and puncture (CLP) surgery. Rats were treated with APS at doses of 400, 600, or 800 mg/kg/day for 7 days. Survival rates, inflammatory cytokine levels, adrenal function, and molecular pathways were evaluated using techniques such as ELISA, HE staining, TUNEL assay, metabolomics, transcriptome sequencing, and validation. Results showed that APS significantly reduced sepsis-induced mortality, elevated serum cortisol levels, and lowered inflammatory cytokines IL-6 and TNF-α. Histological analysis revealed that APS protected the adrenal cortex from apoptosis and inflammatory infiltration. Metabolomic analysis identified 154 differentially regulated metabolites, including significant changes in steroid hormones. Transcriptomic sequencing indicated changes in gene expression, suggesting that APS may inhibit NF-κB activity and promote nitric oxide (NO) production, thus protecting endothelial cells. These findings suggest that APS improves adrenal function and mitigates sepsis-related damage, offering promising therapeutic avenues for sepsis treatment.