Zhang Shijiao, Su Yanding, Han Ao, Qi He, Zhao Jiade, Qiu Xiangjun
College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology, Luoyang 471023, China.
School of Nursing, Henan University of Science and Technology, Luoyang 471003, China.
Pharmaceuticals (Basel). 2025 Jul 25;18(8):1111. doi: 10.3390/ph18081111.
: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive disease that easily develops into cirrhosis and hepatocellular carcinoma, but its pathogenesis is not clear, and most therapeutic drugs have obvious limitations. However, Babao Dan (BBD) has a good therapeutic effect on liver disease, but its treatment mechanism is still to be studied. Therefore, we further investigated the mechanism of BBD in treating MASH. : We predicted BBD-related targets through network pharmacology and further verified the binding ability of BBD-related targets through molecular docking. We also detected relevant indicators before and after model treatment, as well as metabolomics analysis and identification of the mechanism of action of BBD on MASH. : Through network pharmacology methods, 158 key cross targets and the top 10 core targets were identified, and it was determined that the PI3K-AKT signaling pathway plays an important regulatory role in the treatment of MASH with BBD. The molecular docking results indicate that the representative compounds quercetin and 17 Beta Estradiol have good binding activity with five core targets. Metabolomics has identified four metabolic biomarkers, such as Piceid, and it is determined that the key pathway for BBD treatment of MASH is the bile secretion pathway. : BBD effectively treats MASH by modulating Piceid and other biomarkers, targeting ESR1 and other core proteins via quercetin and 17-beta-estradiol, and regulating the PI3K-AKT and bile secretion pathways to alleviate liver injury.
代谢功能障碍相关脂肪性肝炎（MASH）是一种渐进性疾病，易发展为肝硬化和肝细胞癌，但其发病机制尚不清楚，且大多数治疗药物有明显局限性。然而，八宝丹（BBD）对肝病有良好治疗效果，但其治疗机制仍有待研究。因此，我们进一步研究了BBD治疗MASH的机制。我们通过网络药理学预测BBD相关靶点，并通过分子对接进一步验证BBD相关靶点的结合能力。我们还检测了模型治疗前后的相关指标，以及进行代谢组学分析并鉴定BBD对MASH的作用机制。通过网络药理学方法，确定了158个关键交叉靶点和前10个核心靶点，并确定PI3K - AKT信号通路在BBD治疗MASH中起重要调节作用。分子对接结果表明，代表性化合物槲皮素和17β - 雌二醇与五个核心靶点具有良好的结合活性。代谢组学鉴定出了4种代谢生物标志物，如白藜芦醇苷，并确定BBD治疗MASH的关键途径是胆汁分泌途径。BBD通过调节白藜芦醇苷等生物标志物，经槲皮素和17 - β - 雌二醇靶向ESR1等核心蛋白，并调节PI3K - AKT和胆汁分泌途径来减轻肝损伤，从而有效治疗MASH。
