蓝藻外代谢产物的脂质还原活性与细胞毒性筛查

Screening of Lipid-Reducing Activity and Cytotoxicity of the Exometabolome from Cyanobacteria

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Marine Drugs

影响因子:5.4

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

DOI: 10.3390/md22090412

摘要

蓝藻是二次代谢产物的丰富生产者，有部分代谢产物会被排泄到培养基中。然而，蓝藻外代谢组的研究较少，相关的结构和生物活性评估有限。本研究利用HR-ESI-LC-MS/MS对56株蓝藻菌株的外代谢产物进行了表征。细胞毒性通过HepG2和HCT116两种癌细胞系进行评估，脂质还原作用则在斑马鱼幼体和脂肪酸过载的人类肝细胞的脂肪变性模型中测试。GNPS分析揭示多株菌株中存在大量复杂的独特化合物簇，未在公共数据库中找到对应的鉴定。三株菌株对HCT116细胞的存活率产生抑制作用，分别为Tolypotrichaceae BACA0428（30.45%）、Aphanizomenonaceae BACA0025（40.84%）和Microchaetaceae BACA0110（46.61%）。脂质还原作用在斑马鱼幼体中仅由Dulcicalothrix sp. BACA0344暴露引起（60%）。特征分子网络分析显示，这一生物活性与两类黄烷酮高度相关，文献报道其具有脂质还原活性。蓝藻菌株的外代谢组特征揭示其具有丰富的化学多样性，作为新型生物活性化合物的潜在来源，尽管常被忽视。

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.