Shen Duo, Min Jianxin, Chen Jie, Yan Dongmei, Han Jing, Liu Huihui, Yu Xi, Nie Zongxiu, Li Bin
Academician Workstation, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi, China.
Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Anal Chem. 2025 Mar 18;97(10):5688-5697. doi: 10.1021/acs.analchem.4c06682. Epub 2025 Mar 4.
have good therapeutic effects on nonsmall cell lung cancer (NSCLC). Nevertheless, it is still challenging to elucidate the active ingredients and mechanism of action due to their complex chemical composition. To address this, we innovatively combined network pharmacology with spatial metabolomics to comprehensively investigate the active components and the action mechanism in the present study. First, metabolomics of cells treated with the methanol extract of (ASM) utilizing high-resolution ultrahigh-performance liquid chromatography tandem mass spectrometry (HR-UHPLC-MS/MS) revealed 32 changed metabolites and 7 enriched metabolic pathways, confirming the anti-NSCLC effect of ASM and its impact on endogenous metabolites at the cellular level. Then, 69 chemical components in the ASM were identified using HR-UHPLC-MS/MS, followed by the screening of 6 core components and 10 core targets of anti-NSCLC with the help of network pharmacology and molecular docking. Lastly, quercetin, the most abundant compound among the six core active ingredients, was chosen for evaluating its anti-NSCLC effect and the potential mechanism using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). 51 altered endogenous metabolites were screened, and pathway enrichment analysis results were consistent with cell metabolomics, corroborating our network pharmacology predictions. In addition, we also observed the accumulation of three metabolites of quercetin in the tumor tissues. Network pharmacology combined with MSI elucidated the metabolic mechanisms by which treats NSCLC, offering new insights into herbal cancer therapies.
对非小细胞肺癌（NSCLC）具有良好的治疗效果。然而，由于其化学成分复杂，阐明其活性成分和作用机制仍然具有挑战性。为了解决这个问题，我们创新性地将网络药理学与空间代谢组学相结合，在本研究中全面研究其活性成分和作用机制。首先，利用高分辨率超高效液相色谱串联质谱（HR-UHPLC-MS/MS）对用（ASM）甲醇提取物处理的细胞进行代谢组学分析，发现32种变化的代谢物和7条富集的代谢途径，证实了ASM对NSCLC的抗癌作用及其在细胞水平对内源性代谢物的影响。然后，使用HR-UHPLC-MS/MS鉴定了ASM中的69种化学成分，随后借助网络药理学和分子对接筛选出6种核心成分和10个抗NSCLC的核心靶点。最后，选择六种核心活性成分中含量最高的化合物槲皮素，使用基质辅助激光解吸电离质谱成像（MALDI-MSI）评估其抗NSCLC作用和潜在机制。筛选出51种改变的内源性代谢物，途径富集分析结果与细胞代谢组学一致，证实了我们的网络药理学预测。此外，我们还观察到槲皮素的三种代谢物在肿瘤组织中的积累。网络药理学与MSI相结合阐明了ASM治疗NSCLC的代谢机制，为草药癌症治疗提供了新的见解。
