Structural characterization of Auricularia heimuer polysaccharide and its protection against drug-induced liver injury via AMPK/GSK3β, Nrf2/HO-1 signaling and gut microbiota modulation

Abstract

Excessive use of acetaminophen (APAP) significantly contributes to drug-induced liver injury (DILI). Auricularia heimuer polysaccharides have significant hepatoprotective potential, however their mode of action in mitigating DILI is not yet elucidated. This study isolated and purified a novel polysaccharide, Ahp-1, from the fruiting bodies of A. heimuer, with a molecular weight of 270.161 kDa. Structural analysis revealed that the principal glycosidic linkages in Ahp-1 are 6-Gal, 6-Glc, t-Fuc, and 2,6-Gal, which form dimers by cross-linking of polysaccharide chains. Animal studies indicated that Ahp-1 reduces oxidative stress, elevates the relative abundance of beneficial bacteria within the gut microbiota, regulates microbial balance, and promotes the synthesis of favorable metabolites like Trigonelline. Moreover, following fecal microbiota transplantation (FMT), Ahp-FMT augments tight junction proteins and short-chain fatty acids (SCFAs), thus restoring the intestinal barrier. This subsequently stimulates the AMPK/GSK3β and Nrf2/HO-1 signaling pathways to mitigate DILI. These results provide novel opportunities for using A. heimuer polysaccharides as functional foods or hepatoprotective agents.