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从红薯中筛选潜在抗白血病成分:代谢组学分析、网络药理学与实验验证的整合

Screening potential antileukemia ingredients from sweet potato: integration of metabolomics analysis, network pharmacology, and experimental validation.

作者信息

Xu Lianling, Zeng Kaixuan, Duan Zuoyue, Liu Jing, Zeng Yan, Zhang Miao, Yang You, Guo Qulian, Jin Yanling, Liu Wenjun, Guo Ling

机构信息

Department of Pediatrics, Children Hematological Oncology and Birth Defects Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Southwest Medical University, Luzhou, China.

Department of Pediatrics, Southwest Medical University, Luzhou, China.

出版信息

Front Nutr. 2025 Jan 27;12:1518525. doi: 10.3389/fnut.2025.1518525. eCollection 2025.

Abstract

BACKGROUND

Active dietary flavonoids are a promising resource for novel drug discovery. Sweet potato, a widely cultivated functional crop, is abundant in flavonoids. However, the active ingredients associated with acute myeloid leukemia (AML) treatment and their underlying mechanisms have not been reported to date.

OBJECTIVE

This study aims to identify novel drugs against AML from sweet potato by integrating metabolomics analysis, network pharmacology, and experimental validation.

METHODS

Firstly, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed to analyze the major constituents in sweet potato. Then, nine active ingredients were selected for validation of their anti-leukemia effects. Subsequently, three of them underwent network pharmacology analyses and experimental verification. Finally, the anti-leukemia effect of cynaroside was further confirmed through experimental validation.

RESULTS

Firstly, the flavonoid content of stem, leaves, flesh, and peel from 13 sweet potato cultivars was examined. The leaves of Nanshu 017 exhibited the highest flavonoid content of 2.27% dry weight (DW). Then, an extract derived from these leaves was employed for experiments, demonstrating significant inhibition of AML cell growth. Subsequently, based on the results of metabolomics analysis and network pharmacology, cynaroside, nepitrin, and yuanhuanin were identified as potential antileukemia agents present in sweet potato for the first time; while CASP3, KDR, EGFR, and SRC were recognized as pivotal targets of these three monomers against AML. Finally, the antileukemia effects of cynaroside, nepitrin, and yuanhuanin were confirmed through and experimental validation.

CONCLUSION

In summary, sweet potato leaves extract possesses an antileukemic effect while cynaroside, nepitrin, and yuanhuanin demonstrate potential as treatments for AML.

摘要

背景

活性膳食类黄酮是新型药物发现的一个有前景的资源。甘薯是一种广泛种植的功能性作物,富含类黄酮。然而,迄今为止,尚未有与急性髓系白血病(AML)治疗相关的活性成分及其潜在机制的报道。

目的

本研究旨在通过整合代谢组学分析、网络药理学和实验验证,从甘薯中鉴定出抗AML的新型药物。

方法

首先,采用超高效液相色谱串联质谱(UPLC-MS/MS)分析甘薯中的主要成分。然后,选择9种活性成分验证其抗白血病作用。随后,其中3种成分进行了网络药理学分析和实验验证。最后,通过实验验证进一步证实了刺槐苷的抗白血病作用。

结果

首先,检测了13个甘薯品种的茎、叶、果肉和果皮中的类黄酮含量。南薯017叶片的类黄酮含量最高,干重为2.27%。然后,将这些叶片的提取物用于实验,显示出对AML细胞生长的显著抑制作用。随后,基于代谢组学分析和网络药理学的结果,首次鉴定出刺槐苷、荆芥苷和缘藿苷为甘薯中潜在的抗白血病药物;而半胱天冬酶3(CASP3)、激酶插入区受体(KDR)、表皮生长因子受体(EGFR)和肉瘤病毒癌基因(SRC)被认为是这三种单体抗AML的关键靶点。最后,通过实验验证证实了刺槐苷、荆芥苷和缘藿苷的抗白血病作用。

结论

综上所述,甘薯叶提取物具有抗白血病作用,而刺槐苷、荆芥苷和缘藿苷显示出作为AML治疗药物的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3755/11807822/bef8e6ee6755/fnut-12-1518525-g001.jpg

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