Abstract: The objective of this study was to investigate the ameliorative effect and potential mechanism of Cistanche deserticola polysaccharides (CDPs) on diabetic nephropathy (DN) in mice. The DN mouse model was established by high-fat diet (HFD) feeding combined with intraperitoneal injection of streptozotocin (STZ). Thirty-six C57BL/6N male mice were randomly divided into six groups (n = 6 each). All groups were orally administered with distilled water (control and model), dapagliflozin or CDPs for 4 weeks. Changes in physiological indices, renal function, inflammatory factors and the intestinal microbiota were assessed. The results showed that CDPs significantly improved the general condition and attenuated the renal histopathological changes, and reduced the levels of blood glucose, urinary protein and inflammatory factors in DN mice. Additionally, CDPs affected the balance of intestinal microbiota, increased the abundance of beneficial bacteria and decreased potential pathogenic bacteria, which in turn improved intestinal barrier function. CDPs also inhibited the activation of the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway and reduced the release of lipopolysaccharide (LPS). In conclusion, CDPs exhibit an ameliorative effect on DN in mice by affecting the intestinal microbiota and inhibiting inflammatory signaling pathways. This finding offers new insights into the treatment of DN.

Key words: Cistanche deserticola polysaccharides; diabetic nephropathy; intestinal barrier; intestinal flora; Toll-like receptor 4; nuclear factor-κB