Protective effects of Atractylodes macrocephala polysaccharides on acetaminophen-induced liver injury.

BACKGROUND

Drug-induced liver injury (DILI) is a major clinical concern due to its unpredictable nature and lack of effective therapeutic options.

METHODS

This study investigated the hepatoprotective effects of Atractylodes macrocephala polysaccharides (AMPs) in a mouse model of acetaminophen (APAP)-induced liver injury. Mice were pretreated with AMPs for 7 days prior to APAP challenge, and liver injury was evaluated through histopathology, serum biochemistry, molecular assays, and gut microbiota analysis.

RESULTS

AMPs treatment significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared to the APAP group ( < 0.05). Hepatic oxidative stress was alleviated, as indicated by increased levels of glutathione (GSH, < 0.05) and superoxide dismutase (SOD, < 0.05), and reduced malondialdehyde (MDA, < 0.05). AMPs also suppressed inflammatory cytokines, including , , , and ( < 0.05), and modulated apoptosis-related proteins by downregulating and upregulating and expression ( < 0.05). Furthermore, AMPs improved gut microbiota diversity and enriched beneficial genera such as , as revealed by 16S rDNA sequencing. Fecal microbiota transplantation from AMPs-treated mice replicated these hepatoprotective effects, highlighting the involvement of the gut-liver axis.

CONCLUSION

These findings support the therapeutic potential of AMPs as a multifaceted agent for DILI, exerting protective effects through modulation of oxidative stress, inflammation, apoptosis, and intestinal dysbiosis.