School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Pharmacy, Guangdong Second Provincial General Hospital, Guangzhou, China.
Medicine (Baltimore). 2023 Oct 20;102(42):e35675. doi: 10.1097/MD.0000000000035675.
Clinacanthus nutans (for abbreviation thereafter) is often used as medicine in the form of fresh juice in the folk to treat many kinds of cancers, including renal cell carcinoma (RCC). It is speculated that its active ingredient may have heat sensitivity, but there are currently no reports on this aspect. Therefore, based on the folk application for fresh juice of C nutans, this study used metabonomics and network pharmacology to explore the material basis and mechanism of action of C nutans against RCC.
Firstly, untargeted metabolomics profiling was performed by Liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry to screen the metabolites down-regulated by heat in the extract of C nutans. Secondly, we collected the targets of metabolites in the Swiss Target Prediction platform. In addition, the targets of RCC were obtained in the GeneCards database. The "component-target-disease" network was established by Cytoscape3.9.0 software. Then we constructed a protein-protein interaction network in the STRING network platform to screen core targets. The gene ontology and kyoto encyclopedia of genes and genomes enrichment analysis of core targets were carried out to predict the relevant pathway of C nutans in the treatment of RCC. Finally, the molecular docking verification of the core targets were carried out.
In this study, 35 potential active ingredients and 125 potential targets were obtained. And the core targets were Cellular tumor antigen p53, Signal transducer and activator of transcription 3, and so on. Then, 48 biological processes, 30 cell components, and 36 molecular functions were obtained by gene ontology enrichment analysis. Besides, 44 pathways were obtained by Kyoto encyclopedia of genes and genomes enrichment analysis, including Pathway in cancer, PI3K-Akt signal pathway, P53 signal pathway, and so on. The docking model between the core target and its corresponding components was stable.
This research is based on the folk application of C nutans, showed its potential active ingredients by metabonomics, and predicted the potential mechanism of C nutans in the treatment of RCC by network pharmacology. It provides new references for follow-up research and new drug development.
山奈（简称 Cnutans）常以鲜汁入药，民间用于治疗多种癌症，包括肾细胞癌（RCC）。据推测，其有效成分可能具有热敏感性，但目前尚无这方面的报道。因此，本研究基于 Cnutans 鲜汁的民间应用，采用代谢组学和网络药理学方法，探讨 Cnutans 治疗 RCC 的物质基础和作用机制。
首先，采用液质联用和气质联用进行非靶向代谢组学分析，筛选 Cnutans 提取物中受热下调的代谢物。其次，在 Swiss Target Prediction 平台上收集代谢物的靶标。此外，在 GeneCards 数据库中获取 RCC 的靶标。通过 Cytoscape3.9.0 软件建立“成分-靶标-疾病”网络。然后，在 STRING 网络平台上构建蛋白质-蛋白质相互作用网络，筛选核心靶标。对核心靶标进行基因本体论和京都基因与基因组百科全书富集分析，预测 Cnutans 治疗 RCC 的相关通路。最后，对核心靶标进行分子对接验证。
本研究共获得 35 个潜在活性成分和 125 个潜在靶标。核心靶标为细胞肿瘤抗原 p53、信号转导和转录激活因子 3 等。然后，通过基因本体论富集分析得到 48 个生物过程、30 个细胞成分和 36 个分子功能。此外，通过京都基因与基因组百科全书富集分析得到 44 条通路，包括癌症通路、PI3K-Akt 信号通路、p53 信号通路等。核心靶标与相应成分的对接模型稳定。
本研究基于 Cnutans 的民间应用，通过代谢组学显示其潜在的活性成分，并通过网络药理学预测 Cnutans 治疗 RCC 的潜在机制。为后续研究和新药开发提供了新的参考。
