过量的非酯化脂肪酸（NEFA）会损害细胞代谢，并会在围产期期间诱导奶牛形成脂肪肝。黄芩苷是一种活性黄酮类化合物，在缓解脂质堆积和改善脂肪肝疾病的发展方面具有巨大的潜在功效。然而，其机制仍不清楚。在这里，利用网络药理学和体外实验探讨了黄芩苷在系统水平上的潜在机制。首先预测黄芩苷与脂肪肝疾病的作用靶点，然后构建蛋白质-蛋白质相互作用（PPI）网络。此外，京都基因和基因组百科全书 (KEGG)（q 值）途径富集是通过注释、可视化和集成发现数据库 (DAVID) 服务器进行的。最后验证了NEFA体外处理牛肝细胞的网络分析结果。结果显示，通过网络药理学预测黄芩苷治疗脂肪肝的33个相关靶点，并通过KEGG数据库提取前20个相关通路。黄芩苷处理可降低NEFA处理的牛肝细胞中甘油三酯(TAG)含量和脂滴积累，其机制与抑制脂质合成、促进脂质氧化有关。黄芩苷对脂肪肝的缓解作用可能与上调溶质载体家族成员4（SLC2A4）、下调AKT丝氨酸/苏氨酸激酶1（AKT1）、过氧化物酶体增殖物激活受体γ（PPARG）、表皮生长因子受体（EGFR）、肿瘤坏死因子（TNF）、白细胞介素6（IL-6）相关。这些结果表明，黄芩苷可以调节关键的炎症标志物和脂肪生成过程，以预防奶牛脂肪肝的发展。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Excessive nonesterified fatty acids (NEFA) impair cellular metabolism and will induce fatty liver formation in dairy cows during the periparturient. Baicalin, an active flavonoid, has great potential efficacy in alleviating lipid accumulation and ameliorating the development of fatty liver disease. Nevertheless, its mechanism remains unclear. Here, the potential mechanism of baicalin on system levels was explored using network pharmacology and in vitro experiments. Firstly, the target of baicalin and fatty liver disease was predicted, and then the protein-protein interaction (PPI) network was constructed. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) (q-value) pathway enrichment is performed through the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server. Finally, the results of the network analysis of the in vitro treatment of bovine hepatocytes by NEFA were confirmed. The results showed that 33 relevant targets of baicalin in the treatment of liver fatty were predicted by network pharmacology, and the top 20 relevant pathways were extracted by KEGG database. Baicalin treatment can reduce triglyceride (TAG) content and lipid droplet accumulation in NEFA-treated bovine hepatocytes, and the mechanism is related to inhibiting lipid synthesis and promoting lipid oxidation. The alleviating effect of baicalin on fatty liver may be related to the up-regulation of solute vector family member 4 (SLC2A4), Down-regulated AKT serine/threonine kinase 1 (AKT1), Peroxisome proliferator-activated receptor gamma (PPARG), Epidermal growth factor receptor (EGFR), tumor necrosis factor (TNF), Interleukin 6 (IL-6) were associated. These results suggested that baicalin may modulate key inflammatory markers, and lipogenesis processes to prevent fatty liver development in dairy cows.Copyright © 2024 Elsevier B.V. All rights reserved.