School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, P.R. China.
College of Integrated Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, 050200, P.R. China.
Comb Chem High Throughput Screen. 2024;27(18):2667-2680. doi: 10.2174/0113862073273396231010102606.
Cnidii Fructus (CF) is known for its antibacterial, anti-inflammatory, and antitumor properties, as well as its activities against kidney deficiency and impotence. In this study, we aimed to explore the anti-CRC cancer effect and molecular mechanism of CF network pharmacology and antitumor experiments.
Network pharmacology was used to investigate the anti-CRC mechanism of CF. First, a series of databases was used to screen the active phytochemical targets and anti-CRC core targets. Then, the GO and KEGG pathways were analyzed to predict possible mechanisms. Molecular docking analysis explore core targets-phytochemicals interactions. In vitro antitumor experiments were carried on verifying anti-CRC mechanism of CF.
In this study, 20 active ingredient targets and 50 intersecting targets were analyzed by Cytoscape software 3.9.1 to obtain the core genes and phytochemicals. Then, the GO and KEGG pathways of 50 intersecting targets were analyzed to predict possible mechanisms. The results from GO and KEGG indicated that CF has significant antitumor efficacy, which involves many signaling pathways, such as PI3K/AKT and p53. The five core targets and five core phytochemicals were screened for molecular docking to show protein-ligand interactions. According to the results of molecular docking, the compound O-acetylcolumbianetin was selected for the anti- CRC functional verification . MTT assay showed that O-acetylcolumbianetin significantly inhibited the proliferation of colorectal HCT116 cells in a time- and quantity-dependent manner. O-acetylcolumbianetin can promote the expression of CASP3 protein, induce HCT116 cells apoptosis, thus exert anti-CRC effect.
This study preliminarily verified the anti-CRC effect and molecular mechanism of CF and provided a reference for Traditional Chinese Medicine anti-tumor subsequent research.
蛇床子具有抗菌、抗炎和抗肿瘤作用，以及补肾壮阳作用。本研究旨在通过网络药理学和抗肿瘤实验探索蛇床子对 CRC 的抗癌作用及其分子机制。
采用网络药理学方法研究蛇床子对 CRC 的作用机制。首先，利用一系列数据库筛选出蛇床子的活性植物化学物质靶点和抗 CRC 核心靶点。然后，对 GO 和 KEGG 通路进行分析，以预测可能的作用机制。分子对接分析探索核心靶点-植物化学物质相互作用。通过体外抗肿瘤实验验证蛇床子抗 CRC 的作用机制。
本研究通过 Cytoscape 软件 3.9.1 分析了 20 个活性成分靶点和 50 个交集靶点，获得了核心基因和植物化学物质。然后，对 50 个交集靶点的 GO 和 KEGG 通路进行分析，以预测可能的作用机制。GO 和 KEGG 通路分析结果表明，蛇床子具有显著的抗肿瘤功效，涉及 PI3K/AKT 和 p53 等多种信号通路。筛选出五个核心靶点和五个核心植物化学物质进行分子对接，以显示蛋白-配体相互作用。根据分子对接结果，选择化合物 O-乙酰山奈酚进行抗 CRC 功能验证。MTT 试验结果表明，O-乙酰山奈酚能够显著抑制结直肠 HCT116 细胞的增殖，且呈时间和剂量依赖性。O-乙酰山奈酚可促进 CASP3 蛋白的表达，诱导 HCT116 细胞凋亡，从而发挥抗 CRC 作用。
本研究初步验证了蛇床子对 CRC 的抗癌作用及其分子机制，为中药抗肿瘤的后续研究提供了参考。
