基于网络药理学的血清药物化学策略探索岩黄连治疗肝癌的作用机制。
A network pharmacology integrated serum pharmacochemistry strategy for uncovering efficacy of YXC on hepatocellular carcinoma.
机构信息
The First School of Clinical Medicine, Nanjing University of Chinese Medicine, 210023, Nanjing, China.
Yancheng Hospital of Traditional Chinese Medicine, 224000, Yancheng, China.
出版信息
J Ethnopharmacol. 2024 Jan 30;319(Pt 1):117125. doi: 10.1016/j.jep.2023.117125. Epub 2023 Sep 10.
ETHNOPHARMACOLOGICAL RELEVANCE
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.
AIM OF THE STUDY
The treatment mechanism of YXC on HCC using a network pharmacology integrated serum pharmacochemistry strategy to investigate associated targets and pathways.
MATERIALS AND METHODS
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 YXC 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.
RESULTS
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.
CONCLUSIONS
YXC can inhibit HCC development and advancement by a variety of components, targets and pathways, especially apoptosis-induction.
民族药理学相关性
扬征消积胶囊（YXC）作为一种有效的肝癌（HCC）中药制剂，在中国应用广泛。然而，其潜在的生物活性成分和作用机制尚不清楚。
研究目的
采用网络药理学整合血清药化学策略，研究 YXC 治疗 HCC 的作用机制及相关靶点和通路。
材料与方法
我们利用 HPLC-Q-TOF-MS/MS 技术鉴定了荷肝癌裸鼠模型组和 YXC（H）组血清中的成分，然后进行化合物-靶标预测，并鉴定 YXC 组靶基因与 HCC 相关癌基因的重叠。利用京都基因与基因组百科全书（KEGG）通路和基因本体论（GO）分析构建化合物-靶标-通路网络，研究 YXC 的抗癌机制。通过体外和体内实验评估 YXC 的抗癌效果。通过 Western blot 评估 YXC 治疗 HCC 中与潜在预测靶点和通路相关的作用。
结果
YXC（H）血清与其他模型相比有 47 种生物活性化合物，鉴定出 173 个特定的靶基因。利用化合物-靶标-疾病网络，鉴定出 141 个可能的靶基因。KEGG 通路分析显示，与 HCC 相关的关键通路包括炎症、免疫、细胞凋亡和坏死等生物学过程的调控，具有重要的富集作用。YXC 在体外和体内均显著抑制 HCC 细胞生长。YXC 治疗后，Western blot 检测到 p53/Bcl-2/Bax/Caspase-3 和 PI3K/Akt 通路的变化。
结论
YXC 可以通过多种成分、靶点和通路抑制 HCC 的发展和进展，特别是诱导细胞凋亡。
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