Objective To investigate the medication regularity of traditional Chinese medicine (TCM) for preventing and treating alcohol-related liver and brain injuries, and to explore the intervention mechanisms of Jiejiu Formula (JJF) with homology of medicine and food on alcoholic liver disease (ALD) and alcohol-related brain injury (ARBI) through network pharmacology and experimental validation. Methods Herbal formulas targeting ALD and ARBI were collected from TCM classics of the Tang, Song, Yuan, and Ming dynasties. Frequency analysis was performed on the constituent herbs to identify high-frequency ingredients. Their properties, flavors, meridian affinities, and dosages were analyzed. Association rule mining and cluster analysis were then applied to identify a core herbal combination for the JJF. Network pharmacology was used to screen the active components and potential targets of the JJF against ALD and ARBI. Core targets were subjected to gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. Molecular docking and molecular dynamics simulations were employed to validate the predicted mechanisms and binding stability. Subsequently, an alcohol-induced liver and brain injury mouse model was established to verify the findings in vivo. Results A total of 301 formulas containing 263 distinct herbs were identified. Herbs with a warm nature, pungent flavor, stomach meridian affinity, and heat-clearing functions were the most frequently used. The combination of “Gancao (Glycyrrhizae Radix et Rhizoma)-Chenpi (Citri Reticulatae Pericarpium)-Ganjiang (Zingiberis Rhizoma)” demonstrated the highest frequency and strongest association, and all three herbs are classified as medicinal food ingredients. Therefore, this combination was designated as the JJF. Network pharmacology identified 289 active components and 254 potential targets for the JJF against ALD/ARBI. Protein-protein interaction (PPI) network analysis revealed five core targets. KEGG enrichment analysis highlighted pathways related to endocrine resistance. Molecular docking suggested that 2-[(3R)-8,8-dimethyl-3,4-dihydro-2H-pyrano[6,5-f]chromen-3-yl]-5-methoxyphenol and phaseolinisoflavan have good binding affinity and stability with protein kinase B1 (AKT1), which was further confirmed by stable binding in MD simulations. In vivo experiments showed that the JJF alleviated alcohol-induced damage in liver and brain tissues to varying degrees. Conclusion JJF exerts preventive and therapeutic effects against ALD and ARBI. It potentially acts on key targets such as Src proto-oncogene tyrosine-protein kinase (SRC), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA), and AKT1, and modulates pathways like endocrine resistance. Furthermore, the JJF may accelerate alcohol metabolism, enhance anti-oxidative stress capacity, upregulate mRNA expression within the phosphatidylinositol-3-hydroxykinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway, and inhibit mitogen-activated protein kinase 3 (MAPK3) expression, thereby regulating cell proliferation, apoptosis, and inflammatory responses to achieve its protective effects.

data mining  /  homology of medicine and food  /  Glycyrrhizae Radix et Rhizoma-Citri Reticulatae Pericarpium-Zingiberis Rhizoma  /  alcoholic liver disease  /  alcohol-related brain injury