An Investigation of the Toxicity and Mechanisms of Food Additives Based on Network Toxicology and GEO Databases: A Case Study of Aspartame

IF 2.6 3区农林科学 Q2 FOOD SCIENCE & TECHNOLOGY

Food Analytical Methods Pub Date : 2024-05-04 DOI:10.1007/s12161-024-02634-5

Bin Li, Lingyang Shi, Mei Feng, Weichuan Fan, Wenting Lu, Yukai Wang, Zhiqi He, Tao Liu

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Abstract

This study employs network toxicology, molecular docking, and molecular dynamics simulations to assess the characteristics and potential molecular mechanisms of aspartame-induced hepatocellular carcinoma (HCC). Utilizing ChEMBL, STITCH, and SwissTargetPrediction databases, potential target proteins associated with aspartame are identified. HCC-related targets are determined through bioinformatics and weighted gene co-expression network analysis (WGCNA). Gene enrichment analysis explores the signaling pathways related to aspartame-induced HCC. Further refinement using the STRING database and Cytoscape software highlights 15 key targets. Molecular docking, conducted using Autodock Vina, assesses the relationships between aspartame and each key target. Molecular dynamics simulations evaluate the binding capabilities of aspartame with core targets obtained through molecular docking. The results indicate that aspartame may induce HCC by modulating apoptosis and proliferation of liver cancer cells, affecting inflammatory signaling pathways, and regulating estrogen metabolism, posing to the occurrence and development of liver toxicity and associated inflammation, thereby leading to a risk of hepatocarcinogenesis. This study provides a theoretical foundation for understanding the molecular mechanisms underlying aspartame-induced HCC. Additionally, our network toxicology approach accelerates the elucidation of toxic pathways for uncharacterized food additives.

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基于网络毒理学和全球环境展望数据库的食品添加剂毒性和机理调查：阿斯巴甜案例研究

本研究采用网络毒理学、分子对接和分子动力学模拟来评估阿斯巴甜诱发肝细胞癌（HCC）的特征和潜在分子机制。利用 ChEMBL、STITCH 和 SwissTargetPrediction 数据库，确定了与阿斯巴甜相关的潜在靶蛋白。通过生物信息学和加权基因共表达网络分析（WGCNA）确定了与 HCC 相关的靶标。基因富集分析探讨了与阿斯巴甜诱导的 HCC 相关的信号通路。利用 STRING 数据库和 Cytoscape 软件进一步细化，突出了 15 个关键靶点。使用 Autodock Vina 进行的分子对接评估了阿斯巴甜与每个关键靶点之间的关系。分子动力学模拟评估了阿斯巴甜与通过分子对接获得的核心靶点的结合能力。结果表明，阿斯巴甜可能会通过调节肝癌细胞的凋亡和增殖、影响炎症信号通路以及调节雌激素代谢来诱发肝癌，从而导致肝脏毒性和相关炎症的发生和发展，进而引发肝癌的风险。这项研究为了解阿斯巴甜诱导 HCC 的分子机制奠定了理论基础。此外，我们的网络毒理学方法加速了对未定性食品添加剂毒性途径的阐明。

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来源期刊

Food Analytical Methods 农林科学-食品科技

CiteScore

6.00

自引率

3.40%

发文量

244

审稿时长

3.1 months

期刊介绍： Food Analytical Methods publishes original articles, review articles, and notes on novel and/or state-of-the-art analytical methods or issues to be solved, as well as significant improvements or interesting applications to existing methods. These include analytical technology and methodology for food microbial contaminants, food chemistry and toxicology, food quality, food authenticity and food traceability. The journal covers fundamental and specific aspects of the development, optimization, and practical implementation in routine laboratories, and validation of food analytical methods for the monitoring of food safety and quality.