Honey Lemon Alleviates Alcoholic Liver Disease via Multi-Target Synergistic Mechanisms: An Integrated Study of Network Pharmacology, Molecular Docking, and Animal Experiments

Honey lemon (H&L) is a traditional beverage known for its potential liver-protective effects, but its mechanisms against alcoholic liver disease (ALD) remain poorly understood. This study aimed to investigate the hepatoprotective properties of H&L and explore its multi-target mechanisms in alleviating ALD. Using network pharmacology and molecular docking, we identified 26 bioactive compounds in H&L and 335 potential targets associated with ALD. Pathway enrichment analysis revealed that H&L might exert its influence by regulating inflammation, oxidative stress and ethanol metabolism. Molecular docking further demonstrated strong binding interactions between key flavonoids (hesperidin, diosmin, and eriocitrin) and crucial targets, such as AKT1, SRC, STAT3, as well as ethanol-metabolizing enzymes like ADH, ALDH, and CYP2E1. In vivo experiments suggested that H&L alleviated liver injury and significantly improved selected indicators related to ethanol metabolism, oxidative stress, and inflammatory response. For several variables, including ALT/AST, ALDH, IL-6, and hepatic ethanol content, improvement trends were observed, although not all differences reached statistical significance. Overall, the results suggest that the protective effect of H&L against ALD may be associated with a multi-component, multi-target, and multi-pathway mode of action, supporting its potential for further investigation as a functional food candidate.