栀子苷是药食同源中药栀子的主要有效成分，因具有抗炎、抗菌、降血糖、抗抑郁、抗氧化、免疫调节、抗肿瘤等药理活性而备受关注。然而，栀子苷在结肠癌(Colon cancer，CRC)细胞中的靶点和作用机制尚不明确。本文主要通过网络药理学进行栀子苷与CRC共同靶点的筛选，构建栀子苷与CRC的靶蛋白互作网络，采用R语言包进行生物功能(Gene Ontology，GO)和通路(Kyoto Encyclopedia of Genes and Genomes，KEGG)富集分析，发现栀子苷发挥抗CRC作用与肿瘤细胞衰老密切相关。采用药物亲和反应靶点稳定性(Drug affinity responsive target stabil-ity，DARTS)联合质谱探究栀子苷调控CRC细胞衰老的潜在作用靶点，并通过分子对接预测栀子苷与靶蛋白的具体结合位点。结果发现栀子苷能够通过靶向结合脯氨酸异构酶1A(FKBP prolyl isomerase 1A，FKBP1A)发挥抗CRC的作用。细胞功能实验证实栀子苷可以显著诱导CRC细胞衰老。研究结果表明栀子苷可能通过靶向结合FKBP1A从而诱导CRC细胞衰老，这为栀子苷用于CRC治疗的研究和开发提供了理论依据和参考。
To Explore the Mechanism of Geniposide Against Colon Cancer Based on Network Pharmacology
Geniposide is the main bioactive ingredient of traditional Chinese medicine Gardenia jasminoides.It has attracted substan-tial attention due to its pharmacological activities such as anti-inflammatory,antibacterial,hypoglycemic,antidepressant,antioxi-dant,immune modulation,and anti-tumor.However,the target and underlying mechanism of geniposide in colon cancer(CRC)cells remained elusive.Herein,we mainly screened the common targets of geniposide and CRC via network pharmacology,and construct-ed the target protein interaction network,and utilized the R package to perform enrichment analysis of biological functions(GO)and pathways(KEGG).The results indicated that the anti-CRC effect of geniposide is closely associated with cellular senescence.Drug affinity responsive target stability(DARTS)combined with mass spectrometry analysis was conducted to explore the potential tar-gets of geniposide in regulating CRC cell senescence.Moreover,molecular docking was utilized to predict the specific binding sites of geniposide and target proteins.We revealed that geniposide exerted anti-CRC effects by directly targeting FKBP prolyl isomerase 1A(FKBP1A).Cell function experiments further confirmed that geniposide significantly induced CRC cell senescence.Altogether,these results demonstrated that geniposide may trigger CRC cell senescence by targeting FKBP1A,which provides a theoretical ba-sis and reference for the research and development of geniposide for CRC treatment.
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