杨正小剂（YXC）在中国作为有效的中草药制剂广泛应用于肝细胞癌治疗，但其潜在的生物活性成分和机制仍未明确。本研究采用网络药理学和血清药理化学相结合的策略探究YXC在肝细胞癌治疗中的作用机制。我们利用HPLC-Q-TOF-MS/MS技术鉴定了正交移植肝肿瘤裸鼠模型组和YXC(H)组血清样品中的成分，然后进行了化合物靶点预测，并确定了YXC组中与肝细胞癌相关的致癌基因的重叠。通过使用Kyoto Encyclopedia of Genes and Genomes（KEGG）途径和Gene Ontology（GO）分析，创建了一个化合物-靶点-途径网络，研究了YXC的抗癌机制。我们还通过体外和体内评估了YXC的抗癌功效，并通过西方印迹检测评估了YXC在肝细胞癌治疗中的潜在预测靶点和途径。与其他模型相比，YXC(H)血清含有47种生物活性化合物，并鉴定出了173个特异性靶点基因。通过化合物-靶点-疾病网络，确定了141个可能的靶点基因。KEGG途径分析显示，与肝细胞癌相关的途径（炎症、免疫、凋亡和坏死生物过程）具有重要的富集。YXC在体外和体内显著抑制了肝细胞癌细胞的生长。YXC治疗后，西方印迹检测显示了p53/Bcl-2/Bax/Caspase-3和PI3K/Akt通路的改变。YXC通过多种成分、靶点和途径抑制肝细胞癌的发展和进展，尤其是通过诱导凋亡作用。版权所有 © 2023 Elsevier B.V. 发布。

The YangzhengXiaoji capsule (YXC) has a wide range of applications as effective traditional Chinese medicine (TCM) preparation for hepatocellular carcinoma (HCC) in China. However, the potential bioactive components and the mechanisms are yet unclear.The treatment mechanism of YXC on HCC using a network pharmacology integrated serum pharmacochemistry strategy to investigate associated targets and pathways.We utilised HPLC-Q-TOF-MS/MS technology to identify components of the serum samples from both the model group and the YXC(H) group serum, which were collected from nude mice with orthotopic liver tumours. Following this, we conducted compound-target prediction and identified the overlap between the target genes in the YXC group and the oncogenes associated with HCC. The anticancer mechanisms of XYC were investigated by creating a compound-target-pathway network using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis. The anticancer efficacy was evaluated in vitro and in vivo. Also, potential predictive targets and pathways associated with YXC in HCC treatment were assessed by western blotting.The YXC(H) serum had 47 bioactive compounds compared to other models, and identified 173 specific target genes. Using the compound-target-disease network, 141 possible target genes were identified. The KEGG pathway analysis revealed vital enrichment of pathways associated with HCC, including regulating Oncology related pathways of inflammation, immunity, apoptosis, and necrosis biological processes. YXC significantly inhibited HCC cell growth in vitro and in vivo. After YXC treatment, western blotting detected alterations in the p53/Bcl-2/Bax/Caspase-3 and PI3K/Akt pathways.YXC can inhibit HCC development and advancement by a variety of components, targets and pathways, especially apoptosis-induction.Copyright © 2023. Published by Elsevier B.V.