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.
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http://dx.doi.org/10.1016/j.jep.2023.117125 | DOI Listing |
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