Abstract:

This study aims to investigate the ameliorative effects and underlying mechanisms of Polygonatum cyrtonema Hua polysaccharide 1 (PCP1) on alcohol-related liver disease (ALD) in mice, with a focus on analyzing the regulatory role of the adenosine 5'-monophosphate-activated protein kinase α (AMPKα)/silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling pathway. An ALD mouse model was established using chronic alcohol feeding and acute alcohol gavage, with mice randomly assigned to a control group, model group, positive drug group, PCP1 low-dose group, and PCP1 high-dose group. Liver pathological changes were evaluated through HE staining, oil red O staining, and immunohistochemistry. Biochemical methods were used to measure liver function indicators such as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglyceride (TG) levels, while ELISA was employed to determine the levels of inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Western blot was used to analyze the expression of key proteins such as AMPKα, SIRT1, and PGC-1α. The results showed that PCP1 significantly ameliorated alcohol-induced liver damage. HE staining and oil red O staining revealed that PCP1 intervention reduced hepatic steatosis, inflammatory infiltration, hepatocyte ballooning, and necrotic foci. Serological analysis indicated that PCP1 significantly lowered ALT, AST, TC, and TG levels and reduced the secretion of IL-6 and TNF-α. PCP1 also significantly upregulated the expression of proteins related to the AMPKα/SIRT1/PGC-1α pathway. Additional experiments demonstrated that the AMPKα inhibitor compound C significantly attenuated the protective effects of PCP1, suggesting that PCP1's ameliorative effects may be achieved through activation of the AMPKα/SIRT1/PGC-1α signaling pathway. In conclusion, PCP1 improves alcoholic liver injury by regulating the AMPKα/SIRT1/PGC-1α signaling pathway, providing a potential therapeutic strategy for ALD.

Key words:

Polygonatum cyrtonema Hua polysaccharide 1, alcohol-related liver disease, AMPKα/SIRT1/PGC-1α signaling pathway, energy metabolism