Arabinogalactan prevented APAP-induced acute liver injury by regulating the intestinal flora
Abstract
Background: This study aimed to explore the mechanism by which arabinogalactan (AG) inhibited N-acetyl-para-aminophenol (APAP)-induced acute liver injury in mice. The balance of the mouse intestinal flora and the relationship between AG treatment and the PI3K/AKT and NF-κB signaling pathways were evaluated to confirm a liver-gut interaction.
Methods: Mice were administered 2 different doses of AG (150 or 300 mg/kg body weight) by gavage for 7 days and liver injury was induced by a single injection of APAP (250 m/kg). Hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling, and Hoechst 33258 fluorescence staining of liver tissue were used to analyze liver damage. Western blots were used to evaluate expression of proteins related to PI3K/AKT and NF-κB signaling pathways, and changes in the hierarchical structure of the intestinal flora were determined.
Results: AG pretreatment increased the proportion of Lactobacillus and decreased the abundance of species from norank_o_Clostridiaceae and Prevotella in mouse feces compared with APAP-only treated mice. AG pretreatment reversed glutathione depletion and CYP2E1 overexpression, reduced the production of malondialdehyde and 4-hydroxynonenal, and decreased the levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α and interleukin-1β compared with the APAP-only treated mice. The levels of proteins related to the PI3K/AKT signaling pathway were similar between the AG and control groups. AG pretreatment significantly reduced APAP-induced hepatocyte apoptosis and necrosis and inflammatory infiltration into the liver.
Conclusion: PI3K/AKT pathway-mediated BAX expression and the NF-κB signaling cascade were inhibited by AG. AG protected the intestinal flora composition, which subsequently suppressed oxidative stress in the liver, improved the inflammatory response, and reduced hepatocyte apoptosis and necrosis.
