epiglucan and Liver-Diseases--Alcoholic

Alcoholic liver disease (ALD) has become a health issue globally. Laminarin, a low molecular weight marine-derived β-glucan, has been identified with multiple biological activities. In this study, the ameliorative effect on ALD of laminarin isolated from brown algae was investigated. Phenotypic, pathological alterations and biochemical characteristics indicated that laminarin administration (100 mg/kg/day) significantly alleviated liver injury and improved liver function in the alcohol-induced mice. Gene chip results indicated that laminarin treatment caused 52 up-regulated and 13 down-regulated genes in the hepatic tissues of alcohol-induced damage mice, and most of these genes are associated with regulation of oxidative stress (such as CYP450/glutathione-dependent antioxidation), Wnt signaling pathway, retinol metabolism, and cAMP pathway based on GO and KEGG analysis. PPI network analysis indicated that the downstream target genes lied in the hub of the net. Our experiments also confirmed the changed expressions of some target genes. Taken together, these results suggest that laminarin can ameliorate alcohol-induced damage in mice and its molecular mechanism lies in modulating anti-oxidation pathway, WNT pathway, and cAMP pathway, which regulate the expressions of downstream target genes and alleviate alcohol-induced damage. Our study provides new clue to prevent alcohol-induced damage and will be benefit to develop functional foods. PRACTICAL APPLICATIONS: This study verified the positive effect on alcoholic liver disease (ALD) of laminarin, a water-soluble brown algae-derived β-glucan, linked by β-(1,3) glycosidic bonds with β-(1,6) branches. Laminarin significantly alleviated liver injury and improved liver function of ALD mice. Moreover, transcriptomics and bioinformatics analysis further revealed the gene expression patterns, hub targets, and signalings including CYP450/glutathione, Wnt, retinol metabolism, cAMP pathways regulated by laminarin. This research is the first evidence for hepatoprotective effect of laminarin against ALD and its molecular mechanism, which will be advantage to develop functional foods or adjuvant therapy of ALD.

Topics: Animals; beta-Glucans; Ethanol; Glutathione; Liver Diseases, Alcoholic; Mice; Vitamin A

Alcoholic liver disease (ALD) is caused by long-term consumption of alcohol and has become an important social and medical problem. Intestinal fungal flora (mycobiota) play an important role in ALD, so we used the mycobiota as an entry point to explore the mechanism of action of Paeonol against ALD. Here, we found that Paeonol is effective against ALD inflammatory lesions and relieves liver fat lesions. Furthermore, we found that after the treatment of Paeonol, the fungal dysbiosis is improved, and the fungal abundance is reduced, and the translocation of β-glucan to the liver and its mediated Dectin-1/IL-1β signaling pathway is blocked. Our study shows that paeonol ameliorated acute ALD-related inflammatory injury to the liver by alleviating intestinal fungal dysbiosis and inhibiting the mycobiota-mediated Dectin-1/IL-1β signaling pathway.

Topics: Acetophenones; Alanine Transaminase; Animals; Aspartate Aminotransferases; beta-Glucans; Caspase 1; Cholesterol; Cluster Analysis; Dysbiosis; Inflammation; Interleukin-1beta; Intestinal Mucosa; Kupffer Cells; Lectins, C-Type; Lipogenesis; Liver; Liver Diseases, Alcoholic; Male; Mice, Inbred C57BL; Mycobiome; NLR Family, Pyrin Domain-Containing 3 Protein; Proteoglycans; Signal Transduction; Triglycerides