Protective Effects of <i>Schizochytrium</i> Microalgal Fatty Acids on Alcoholic Liver Disease: A Network Pharmacology and <i>In Vivo</i> Study

<i>This study aimed to elucidate the hepatoprotective mechanisms of microalgal fatty acids (MFA) from <i>Schizochytrium</i> against alcoholic liver disease (ALD) through network pharmacology and <i>in vivo</i> analysis. Network pharmacology and molecular docking methodologies were employed to predict the potential mechanisms of MFA against ALD. To substantiate these predictions, an acute alcoholic liver injury mouse model was utilized to assess the impact of MFA on serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total protein (TP), and albumin (ALB). Additionally, liver histopathology and the expression levels of phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT) protein were evaluated. Seven active ingredients and 53 potential targets (including 7 core targets) for ALD treatment were identified in MFA. Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that these seven core targets are implicated in various biological pathways, notably those associated with cancer, viral infections, and the PI3K/AKT signaling pathway. Furthermore, molecular docking studies demonstrated that docosahexaenoic acid and docosapentaenoic acid in MFA exhibited strong binding affinity for these seven crucial targets. Animal experiments demonstrated that administration of MFA significantly decreased the levels of AST, ALT, and ALP, while increasing the levels of ALB and TP in mice with acute alcoholic liver injury. Moreover, MFA ameliorated liver tissue pathology and markedly down-regulated the expression of PI3K and AKT proteins in the liver. These results suggest that MFA may possess therapeutic potential for ALD by targeting multiple pathways, with its mechanisms likely involving the inhibition of the PI3K/AKT signaling pathway.</i>