Abstract: Objective: To investigate the protective effects of Ganoderma atrum polysaccharides (GAP) against cadmium (Cd)-induced intestinal epithelial barrier injury in Caco-2 cells. Methods: A Caco-2 cell injury model was established by exposure to 3 μg/mL Cd for 12 h, followed by intervention with GAP. After the treatment, epithelial barrier permeability, oxidative stress, inflammation, mitochondrial function, and other related indices were measured. The mRNA expression of genes associated with intestinal barrier function, inflammation and mitochondrial function was determined by real-time quantitative polymerase chain reaction (real-time PCR). Results: Under exposure to 3 μg/mL Cd, the treatment with 320 μg/mL GAP increased Caco-2 cell viability, slowed the decline in transepithelial electrical resistance, elevated alkaline phosphatase activity and partially reversed the Cd-induced down-regulation of tight junction-related genes. GAP also enhanced superoxide dismutase and catalase activities, and reduced malondialdehyde, reactive oxygen species, tumor necrosis factor α and interleukin 6 levels. At the same time, GAP downregulated MyD88 and NF-κB p65 mRNA expression, thereby alleviating Cd-induced oxidative stress and inflammatory responses. GAP alleviated mitochondrial dysfunction, as shown by mitigation of mitochondrial membrane potential loss, ATP depletion, Ca2+ overload and mitochondrial fragmentation, together with upregulation of SIRT1, AMPKα1 and PGC-1α mRNA expression. These findings suggest that GAP may protect mitochondria via regulating the sirtuin 1/adenosine 5’-monophosphate-activated protein kinase α1/peroxisomeproliferator-activated receptor γ coactivator 1α signaling pathway. Conclusion: GAP alleviates Cd-induced intestinal epithelial barrier injury in Caco-2 cells, potentially by reducing oxidative stress and inflammation, improving mitochondrial function, and partially reversing the downregulation of tight junction-related gene expression.

Key words: Ganoderma atrum polysaccharides; cadmium; intestinal epithelial barrier; oxidative stress; mitochondrial function