目的：本研究旨在评估茵栀黄（Yinzhihuang,YZH）对酒精性肝病（alcohol-associated liver disease,ALD）的影响,并结合网络药理学探究其对酒精诱导小鼠肝损伤的可能机制。方法：将4~6周龄雄性C57BL/6小鼠通过Lieber-DeCarli饮食^[1]喂养法构建慢性酒精性肝病小鼠模型,随机分为3组：（1）对照组（Pair-fed）;（2）酒精组（EtOH-fed）;（3）YZH给药组（EtOH-fed+YZH）。对照组每日给予等热量的对照饲料,酒精组每日给予5%（v/v）的酒精饲料,YZH给药组在酒精饲料喂养的基础上每日给予YZH（0.5 mL/kg）。通过血清谷丙转氨酶（alanine aminotransferase,ALT）、谷草转氨酶（aspartate transaminase,AST）水平和组织学评估肝损伤程度,qRT-PCR检测脂质代谢、合成和炎症因子mRNA水平变化。利用TCMSP数据库收集成分及预测靶点,运用TTD、OMIM、DRUGBANK数据库获取 ALD 疾病靶点,并经 Venny2.1.0 获得交集。使用STRING 数据库构建蛋白互相作用的PPI网络,通过Metascape数据库对交集靶点进行 GO功能与KEGG 通路富集。结果：与对照组相比,酒精组小鼠AST和TG水平升高,肿瘤坏死因子（tumor necrosis factor,TNF））-α、白细胞介素（interleukin,IL）-1β、SREBP-1c mRNA水平增加,PPAR-α mRNA水平降低,TNF-α、F4/80蛋白水平升高。YZH给药组可显著降低小鼠饮酒后血清中AST水平,改善酒精诱导的脂质堆积,血清TG水平显著降低,并在mRNA水平与蛋白水平明显减少免疫细胞的浸润和肝脏炎症。网络药理学揭示YZH中75种有效成分,其中槲皮素、芦荟大黄素可能为主要有效成分;可能作用于 95个与 ALD 相关的靶点,包括肿瘤坏死因子、白细胞介素-6、白蛋白、白细胞介素-1β、前列腺素内过氧化物合成酶2等ALD病理进程相关的关键靶点。主要涉及转录调控、脂质稳态、DNA 损伤凋亡等生物过程;KEGG 富集提示YZH调节ALD可能涉及 PI3K/Akt 信号等关键通路。结论：YZH可有效改善酒精诱导的肝损伤、脂质堆积及炎症反应。其关键活性成分槲皮素、芦荟大黄素等成分作用于多靶点,参与多通路的调控,通过抗炎、抑制氧化应激等通路发挥治疗ALD的作用。

Objective This research is intended to assess the influence of Yinzhihuang (YZH) in Alcohol-associated Liver Disease and explore its potential mechanisms in alcohol-induced liver injury in mice using network pharmacology. Methods A chronic alcoholic liver disease mouse model was constructed in 4- to 6-week-old male C57BL/6 mice using the Lieber-DeCarli diet feeding method. The mice were randomly divided into three groups: (1) the control group (Pair-fed); (2) the alcohol group (EtOH-fed); (3) the YZH treatment group (EtOH-fed+YZH). The control group was fed a calorie-matched control diet daily, the alcohol group was fed a diet containing 5% (v/v) ethanol daily, and the YZH treatment group was administered YZH (0.5 mL/kg) daily in addition to the ethanol diet. Liver injury was evaluated through serum ALT and AST levels and histological analysis, while changes in mRNA levels of lipid metabolism, synthesis, and inflammatory factors were measured using qRT-PCR. Components are collected and targets are predicted via the TCMSP database, while ALD disease targets are retrieved from TTD, OMIM, and DRUGBANK databases. Subsequently, the intersection is obtained using Venny2.1.0. The protein-protein interaction (PPI) network is constructed using the STRING database, and the intersecting targets are subjected to GO function and KEGG pathway enrichment analysis via the Metascape database. Results Compared with the control group, the levels of AST and TG in the alcohol group of mice were increased, and the mRNA levels of TNF-α, IL-1β, and SREBP-1c were elevated. Meanwhile, the mRNA level of PPAR-α was decreased, and the protein levels of TNF-α and F4/80 were increased. The YZH treatment group significantly reduced the serum AST levels in mice after alcohol consumption (P<0.05), alleviated alcohol-induced lipid accumulation, and significantly decreased serum TG levels. It also markedly reduced immune cell infiltration and liver inflammation at both the mRNA and protein levels. Pharmacological network analysis revealed 75 active components in YZH, among which quercetin and aloin may be the primary active components. These components may act on 95 targets related to Alcohol-associated Liver Disease (ALD), including tumor necrosis factor (TNF), interleukin-6 (IL-6), albumin (ALB), interleukin-1β (IL-1β), and prostaglandin-endoperoxide synthase 2 (PTGS2), which are key targets involved in the pathological process of ALD. The primary biological processes involved include transcriptional regulation, lipid homeostasis, and DNA damage-induced apoptosis. KEGG enrichment analysis suggests that the regulation of ALD by YZH may involve key pathways such as the PI3K/Akt signaling pathway. Conclusion YZH has been shown to effectively improve alcohol-induced hepatic injury, lipid accumulation, and inflammatory responses. This efficacy is attributed to its key active components, such as quercetin and aloin, which target multiple sites and participate in the regulation of multiple pathways. These components exert therapeutic effects on alcoholic liver disease (ALD) through anti-inflammatory and anti-oxidative stress pathways.