Bioactive Metabolites from Lactobacillus acidophilus-Fermented Products Mitigate Carbon Tetrachloride-Induced Liver Injury: Biochemical and In Silico Insights.

BACKGROUND

Fermented products derived from Lactobacillus have demonstrated therapeutic potential in the management of metabolic disorders, particularly liver diseases.

OBJECTIVES

This study aimed to evaluate the hepatoprotective effects of Lactobacillus-fermented products in a carbon tetrachloride (CCl4)-induced murine model of liver damage, with a focus on analyzing the influence of bioactive compounds on key liver function biomarkers.

METHODS

Two Lactobacillus strains (Lactobacillus acidophilus LB-CARS1 and L. acidophilus ST-CARS2) were isolated from commercial yogurts, and milk was fermented using each strain. A total of 40 male Swiss Albino mice were allocated into 5 experimental groups: control, CCl4-only, CCl4 + silymarin, and 2 treatment groups receiving CCl4 plus 1 of the 2 lactic acid bacteria (LAB)-fermented products. After 6 wk, serum concentrations of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin, and creatinine were measured. A protein-protein network was constructed using the proteins responsible for hepatoprotection. The cellular pathways of these proteins were also visualized by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Molecular docking was performed to assess interactions between identified bioactive compounds and target proteins (superoxide dismutase, catalase, transforming growth factor-β 1, peroxisome proliferator-activated receptor γ, IL-6, and tumor necrosis factor-α).

RESULTS

Treatment with LAB-fermented products significantly reduced (P < 0.05) serum AST, ALT, ALP, bilirubin, and creatinine concentrations in the CCl4-treated mice. The 2 products reduced the liver enzymes, though their intensity was different. The interactive pathways of the protein network revealed the most common genes responsible for hepatoprotective activity. Molecular docking revealed strong binding affinities between bioactive compounds and proteins related to inflammation and oxidation. Furthermore, absorption, distribution, metabolism, excretion, and toxicity analysis suggested the potential drug candidates among the docked compounds.

CONCLUSIONS

The results indicate that LAB-fermented products contain bioactive compounds capable of attenuating liver injury, likely through anti-inflammatory and antioxidant mechanisms, highlighting their potential as functional food interventions in hepatoprotection.