Feng Zhong, Ou Ling, Li Hui, Hao Yajie, Wei Ruixia, Zhang Guimin, Yao Meicun
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Shenzhen, 518107, China.
International Pharmaceutical Engineering Lab of Shandong Province, Feixian, Shandong, 273400, China.
BMC Complement Med Ther. 2025 Apr 17;25(1):142. doi: 10.1186/s12906-025-04871-5.
Hezi Qingyou Formula (HZQYF) is a clinical formulation known for its efficacy in treating gastrointestinal diseases. Nevertheless, its specific impact and underlying mechanism of action in gastric cancer remain to be fully elucidated. The major components of the formula were precisely identified and characterized using ultra-high-performance liquid chromatography coupled with a tandem mass spectrometer (UHPLC-MS/MS). Network pharmacology and transcript analysis were utilized to identify the targets associated with drug-disease interactions. Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome analyses were conducted to unravel the pivotal pathways involved. Furthermore, in vitro experiments were performed to validate the anti-gastric cancer activity of HZQYF, including assessments of cell viability and clonogenic potential. These results revealed that 260 co-expressed targets were identified as shared between HZQYF and gastric cancer. These genes were significantly enriched in biological processes and pathways related to steroid metabolism, gamma-aminobutyric acid (GABA)-A receptor complex, steroid binding activity, extracellular ligand-gated ion channel activity, chemical carcinogenesis-reactive oxygen species, and GABAergic synapse. Furthermore, the principal components of the formula were characterized. Subsequent cell experiments confirmed the formula's ability to inhibit gastric cancer activity and suppress colony formation in vitro. In conclusion, these findings suggest that Hezi Qingyou Formula may exert its anti-gastric cancer activity by influencing reactive oxygen species and modulating GABAergic synapses in-silico methods. This study provides a foundation for further exploration of HZQYF as a potential therapeutic agent for gastric cancer.
诃子清幽方(HZQYF)是一种在治疗胃肠道疾病方面疗效显著的临床配方。然而,其在胃癌中的具体影响和潜在作用机制仍有待充分阐明。采用超高效液相色谱-串联质谱联用仪(UHPLC-MS/MS)对该配方的主要成分进行了精确鉴定和表征。利用网络药理学和转录组分析来确定与药物-疾病相互作用相关的靶点。随后,进行了基因本体论(GO)、京都基因与基因组百科全书(KEGG)和Reactome分析,以揭示其中涉及的关键途径。此外,还进行了体外实验,以验证HZQYF的抗胃癌活性,包括评估细胞活力和克隆形成潜力。这些结果表明,共鉴定出260个HZQYF和胃癌之间的共表达靶点。这些基因在与类固醇代谢、γ-氨基丁酸(GABA)-A受体复合物、类固醇结合活性、细胞外配体门控离子通道活性、化学致癌-活性氧以及GABA能突触相关的生物学过程和途径中显著富集。此外,还对该配方的主要成分进行了表征。随后的细胞实验证实了该配方在体外具有抑制胃癌活性和抑制集落形成的能力。总之,这些发现表明,诃子清幽方可能通过影响活性氧和调节GABA能突触,以计算机模拟方法发挥其抗胃癌活性。本研究为进一步探索HZQYF作为胃癌潜在治疗药物奠定了基础。