目的 探讨中医药防治酒精性肝、脑损伤的用药规律，利用网络药理学及实验验证方法阐释药食同源解酒方对酒精性肝损伤（alcoholic liver disease，ALD）、酒精性脑损伤（alcohol-related brain injury，ARBI）的干预作用机制。方法 筛选唐、宋、元、明时期方书中防治ALD、ARBI的方剂，对处方包含单味中药进行频次统计，分析高频中药的功效、性味归经和剂量，并进行关联规则及聚类分析，挖掘核心中药组合组成解酒方。应用网络药理学筛选解酒方防治ALD、ARBI的核心药物成分和作用靶点，利用基因本体论（gene ontology，GO）与京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）富集分析核心靶点，并辅以分子对接技术和分子动力学模拟验证解酒方防治ALD、ARBI的潜在作用机制。构建酒精性肝、脑损伤小鼠模型，开展体内实验验证。结果 共筛选301首防治ALD、ARBI的方剂，包含263味中药。其中，性温、味辛、归胃经和清热类中药应用频数最高。“甘草-陈皮-干姜”这一组合显示出最高的出现频率与关联强度，且三者均为经典的药食同源中药，将其确定为药食同源解酒方（简称解酒方）。通过网络药理学获得解酒方活性成分102个，防治ALD、ARBI的254个潜在作用靶点，进一步分析蛋白质相互作用（protein-protein interaction，PPI）网络获得5个核心靶点。KEGG通路分析主要集中在内分泌抵抗。分子对接结果提示，5ʹ-O-甲基光甘草定、菜豆异黄烷与蛋白激酶B1（protein kinase B1，AKT1）具有良好的结合能力和稳定性。分子动力学模拟证实菜豆异黄烷-AKT1复合物稳定且结合紧密。体内实验结果表明，解酒方能不同程度改善酒精诱导的小鼠肝、脑组织损伤。结论 解酒方可作用于非受体蛋白酪氨酸激酶（Src proto-oncogene tyrosine-protein kinase，SRC）、磷脂酰肌醇3-激酶催化亚基α亚型（phosphatidylinositol 3-kinase catalytic subunit alpha，PIK3CA）、AKT1等潜在靶点，并且通过内分泌抵抗等信号通路发挥防治ALD、ARBI的作用；同时能够加速酒精代谢、提高抗氧化应激能力以及增强磷脂酰肌醇-3-羟激酶（phosphatidylinositol-3-hydroxykinase，PI3K）/AKT/哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）信号通路的蛋白表达，抑制丝裂原活化蛋白激酶3（mitogen-activated protein kinase 3，MAPK3）表达调控细胞增殖、凋亡与炎症反应，从而发挥防治ALD、ARBI的作用。

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.

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国家中药材产业技术体系专项项目（CARS-21）；黑龙江省自然科学基金重点项目（ZL2024H015）；黑龙江省卫生健康委课题（20251313050527）；黑龙江省中医药科学院科研项目（ZY2025-JK004）