Abstract: Objective: To investigate the alleviative effect and mechanism of Polygonatum sibiricum polysaccharide (PSP) on cadmium (Cd)-induced pancreatic injury in rats. Methods: Twenty-four SPF-grade four-week-old female Sprague Dawley (SD) rats were divided into three groups: control (Con), cadmium-exposed (Cd), and PSP intervention (Cd + PSP) groups. The rats from the Cd group were exposed to cadmium chloride (50 mg/L) via drinking water to establish a model of pancreatic injury, while those from the Cd + PSP group received Cd exposure and PSP gavage (125 mg/(kg·d)) concurrently. After eight weeks of intervention, body mass, fasting blood glucose (FBG), pancreatic cadmium content, and histopathological changes were measured. The association between pancreatic metabolites and the gut microbiota were analyzed using metabolomics and 16S rRNA sequencing. Results: Compared with the Cd group, the Cd + PSP group showed a significant increase in body mass (P < 0.05) and a significant reduction in FBG and pancreatic cadmium content (P < 0.05). Hematoxylin-eosin staining revealed that PSP alleviated Cd-induced pancreatic islet atrophy and structural damage to ileal villi. Metabolomic analysis demonstrated that PSP ameliorated Cd-induced abnormal amino acid metabolism (e.g., phenylalanine metabolism). Gut microbiota analysis indicated that PSP enhanced alpha diversity (Chao1 and Shannon index) and beta diversity, reconstructed the probiotic interaction network, and suppressed pathogenic bacteria (Enterobacteriaceae). Conclusion: PSP significantly mitigates Cd-induced pancreatic injury in rats through multiple mechanisms including reducing cadmium accumulation, repairing the intestinal barrier, improving pancreatic metabolic disorders, and regulating gut microbiota balance. This study provides a theoretical basis for developing PSP-based functional products.

Key words: Polygonatum sibiricum polysaccharide; cadmium; pancreas; metabolomics; gut microbiota