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全基因组规模代谢重建、基于非靶向液相色谱-四极杆飞行时间质谱的代谢组学数据以及叶提取物抗癌活性评估

Genome-Scale Metabolic Reconstruction, Non-Targeted LC-QTOF-MS Based Metabolomics Data, and Evaluation of Anticancer Activity of Leaf Extracts.

作者信息

Camargo Fidias D González, Santamaria-Torres Mary, Cala Mónica P, Guevara-Suarez Marcela, Restrepo Silvia Restrepo, Sánchez-Camargo Andrea, Fernández-Niño Miguel, Corujo María, Gallo Molina Ada Carolina, Cifuentes Javier, Serna Julian A, Cruz Juan C, Muñoz-Camargo Carolina, Gonzalez Barrios Andrés F

机构信息

Group of Product and Process Design, Department of Chemical and Food Engineering, Universidad de los Andes, Bogotá 111711, Colombia.

Applied Genomics Research Group Vice-Presidency for Research and Creation, Universidad de los Andes, Bogotá 111711, Colombia.

出版信息

Metabolites. 2023 Jun 24;13(7):788. doi: 10.3390/metabo13070788.

DOI:10.3390/metabo13070788
PMID:37512495
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10385671/
Abstract

Over the past decades, Colombia has suffered complex social problems related to illicit crops, including forced displacement, violence, and environmental damage, among other consequences for vulnerable populations. Considerable effort has been made in the regulation of illicit crops, predominantly , leading to advances such as the legalization of medical cannabis and its derivatives, the improvement of crops, and leaving an open window to the development of scientific knowledge to explore alternative uses. It is estimated that can produce approximately 750 specialized secondary metabolites. Some of the most relevant due to their anticancer properties, besides cannabinoids, are monoterpenes, sesquiterpenoids, triterpenoids, essential oils, flavonoids, and phenolic compounds. However, despite the increase in scientific research on the subject, it is necessary to study the primary and secondary metabolism of the plant and to identify key pathways that explore its great metabolic potential. For this purpose, a genome-scale metabolic reconstruction of is described and contextualized using LC-QTOF-MS metabolic data obtained from the leaf extract from plants grown in the region of Pesca-Boyaca, Colombia under greenhouse conditions at the Clever Leaves facility. A compartmentalized model with 2101 reactions and 1314 metabolites highlights pathways associated with fatty acid biosynthesis, steroids, and amino acids, along with the metabolism of purine, pyrimidine, glucose, starch, and sucrose. Key metabolites were identified through metabolomic data, such as neurine, cannabisativine, cannflavin A, palmitoleic acid, cannabinoids, geranylhydroquinone, and steroids. They were analyzed and integrated into the reconstruction, and their potential applications are discussed. Cytotoxicity assays revealed high anticancer activity against gastric adenocarcinoma (AGS), melanoma cells (A375), and lung carcinoma cells (A549), combined with negligible impact against healthy human skin cells.

摘要

在过去几十年里,哥伦比亚遭受了与非法作物相关的复杂社会问题,包括强迫流离失所、暴力以及环境破坏等,这些都给弱势群体带来了诸多其他后果。在非法作物管制方面已付出了巨大努力,主要成果包括医用大麻及其衍生物的合法化、作物改良,并为科学知识发展以探索替代用途打开了一扇窗。据估计,[植物名称]能产生约750种特殊次生代谢产物。除大麻素外,一些因其抗癌特性而最为相关的物质有单萜类、倍半萜类、三萜类、精油、黄酮类和酚类化合物。然而,尽管关于该主题的科学研究有所增加,但仍有必要研究该植物的初级和次级代谢,并确定挖掘其巨大代谢潜力的关键途径。为此,利用从哥伦比亚佩斯卡 - 博亚卡地区温室条件下种植于Clever Leaves设施的植物叶片提取物中获得的液相色谱 - 四极杆飞行时间质谱(LC - QTOF - MS)代谢数据,对[植物名称]进行了全基因组规模的代谢重建并进行了背景分析。一个具有2101个反应和1314种代谢物的区室化模型突出了与脂肪酸生物合成、类固醇和氨基酸相关的途径,以及嘌呤、嘧啶、葡萄糖、淀粉和蔗糖的代谢。通过代谢组学数据鉴定出了关键代谢物,如神经碱、大麻ativine、大麻黄素A、棕榈油酸、大麻素、香叶基对苯二酚和类固醇。对它们进行了分析并整合到重建中,并讨论了它们的潜在应用。细胞毒性试验显示对胃腺癌(AGS)、黑色素瘤细胞(A375)和肺癌细胞(A549)具有高抗癌活性,而对健康人类皮肤细胞的影响可忽略不计。

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