红曲桔霉素致毒机理的网络药理学分析

Toxicity Mechanism of Citrinin in Monascus Analyzed by Network Pharmacology

摘要:

为探讨红曲中桔霉素导致毒性的内在机理，通过搜索Swiss Target Prediction、Similarity ensemble approach、Comparative Toxicogenomics Database和GeneCards数据库，利用Metascape、Kobas 3.0、Cytoscape 3.7.2和AutoDock软件，开展了网络药理学分析。结果显示，通过筛选去重获得桔霉素与“liver toxicity”和“kidney toxicity”相关的潜在靶点110个，GO 富集分析功能条目496条，其中涉及分子功能、生物过程和细胞组成的条目分别为97、354和45条。KEGG信号通路富集靶点数和显著性均较高的是肿瘤MicroRNA通路、肿瘤通路、乙型肝炎等通路。桔霉素可能通过TP53、CASP3、MAPK3和ALB等关键靶点导致肝肾毒性。分子对接实验证明，桔霉素与靶点可以结合，揭示了桔霉素导致肝肾毒性的潜在作用靶点和信号通路，为进一步研究桔霉素致毒机理和健康防护提供理论参考。

Abstract:

In order to explore the mechanism of toxicity induced by citrinin in Monascus, the databases of Swiss Target Prediction, Similarity ensemble approach, Comparative Toxicogenomics Database and GeneCards were searched, and the software of Metascape, Kobas 3.0, Cytoscape 3.7.2 and AutoDock were employed for network pharmacology analysis. The results showed that a total of 110 potential targets, which showed the relationship between citrinin and liver toxicity as well as kidney toxicity, were achieved after filter and deduplication. There were 496 items enriched by GO analysis, including 97 molecular function, 354 biological process and 45 cell composition. The KEGG signal pathways with more enriched targets and higher significance mainly included MicroRNAs in cancer, Patyways in cancer, Hepatitis B and so on. Citrinin might induce hepatorenal toxicity through targets of TP53, CASP3, MAPK3 and ALB, and the molecular docking experiments showed that citrinin could bind to these targets. The potential targets and related signal pathways of citrinin-induced hepatorenal toxicity were revealed, providing theoretical reference for further study on the mechanism of citrinin-induced toxicity and health protection.