Effects of Cordyceps Polysaccharides on D-Galactose-induced Renal Senescence

Chronic kidney disease (CKD) poses a significant global health concern. Aging of renal tubular epithelial cells (RTECs) impairs kidney regeneration and repair and promotes CKD progression through the release of the senescence-associated secretory phenotype (SASP). Cordyceps sinensis, whose key bioactive constituents include Cordyceps polysaccharides (CCP), is incorporated into multiple clinical preparations for CKD and has demonstrated therapeutic benefits. To examine the role of CCP in renal aging, a D-galactose-induced renal senescence model was established in mice, with CCP administered as an intervention. Treatment outcomes were evaluated using senescence-related staining and assessments of renal function. A D-galactose-induced aging model in HK-2 cells was further established to investigate underlying cellular mechanisms. JC-1 staining and reactive oxygen species (ROS) detection were used to assess mitochondrial changes following CCP treatment under senescent conditions. Immunofluorescence, western blotting, and quantitative PCR (RT-PCR) were performed to evaluate the effects of CCP on MAPK phosphorylation, NF-κB nuclear translocation, and NLRP3 inflammasome activation. The results show that CCP attenuates tubulointerstitial cell senescence, renal injury, and fibrosis, while improving mitochondrial function in both cellular and animal models of D-galactose-induced senescence. These effects are associated with modulation of the ROS/MAPK/NF-κB/NLRP3 signaling pathway.