从蓝细菌中筛选脂质还原活性和细胞毒性的细胞毒性
Screening of Lipid-Reducing Activity and Cytotoxicity of the Exometabolome from Cyanobacteria
影响因子:5.40000
分区:医学2区 / 药物化学2区 药学2区
发表日期:2024 Sep 10
作者:
Rúben Luz, Rita Cordeiro, Vítor Gonçalves, Vitor Vasconcelos, Ralph Urbatzka
摘要
蓝细菌是次要代谢产物的丰富生产国，将其中一些排泄到了培养基中。然而，研究蓝细菌的外能代谢组的研究很少，很少有研究对其表征和生物活性评估。在这项工作中，通过HR-ESI-LC-MS/MS表征了56种蓝细菌菌株的外化代谢组。在两种癌细胞系HEPG2和HCT116上评估了细胞毒性，而在斑马鱼幼虫和具有脂肪酸肥大的人肝细胞的脂质降低中，脂质的降低进行了测试。使用GNP的外态代谢组分析揭示了多种菌株中许多独特化合物的复杂簇，在公共数据库中没有识别。三个菌株降低了HCT116细胞的生存能力，即tolypotrichaceae baca0428（30.45％），芳族氨基苯二甲酸BACA0025（40.84％）和Microchaetaceae BACAE BACA0110（46.61％）。仅通过暴露于Dulcicalothrix sp。才能观察到斑马鱼幼虫的脂质减少。 BACA0344（60％）。基于特征的分子网络表明，这种生物活性与两种黄酮高度相关，两种黄酮是文献中描述的一种化合物类别，用于具有脂质还原活性。蓝细菌菌株的外态代谢组表征显示出很高的化学多样性，尽管大多数时候都被忽略了，但它支持它作为新型生物活性化合物的来源。
Abstract
Cyanobacteria are rich producers of secondary metabolites, excreting some of these to the culture media. However, the exometabolome of cyanobacteria has been poorly studied, and few studies have dwelled on its characterization and bioactivity assessment. In this work, exometabolomes of 56 cyanobacterial strains were characterized by HR-ESI-LC-MS/MS. Cytotoxicity was assessed on two carcinoma cell lines, HepG2 and HCT116, while the reduction in lipids was tested in zebrafish larvae and in a steatosis model with fatty acid-overloaded human liver cells. The exometabolome analysis using GNPS revealed many complex clusters of unique compounds in several strains, with no identifications in public databases. Three strains reduced viability in HCT116 cells, namely Tolypotrichaceae BACA0428 (30.45%), Aphanizomenonaceae BACA0025 (40.84%), and Microchaetaceae BACA0110 (46.61%). Lipid reduction in zebrafish larvae was only observed by exposure to Dulcicalothrix sp. BACA0344 (60%). The feature-based molecular network shows that this bioactivity was highly correlated with two flavanones, a compound class described in the literature to have lipid reduction activity. The exometabolome characterization of cyanobacteria strains revealed a high chemodiversity, which supports it as a source for novel bioactive compounds, despite most of the time being overlooked.