Ding Haoxuan, Chen Lingjun, Hong Zuopeng, Yu Xiaonan, Wang Zhonghang, Feng Jie
College of Animal Sciences, Zhejiang University, Key Laboratory of Animal Feed and Nutrition of Zhejiang Province, Hangzhou 310058, China.
Research Center of Zhejiang Weifeng Biotechnology Co., Ltd, Hangzhou 310000, China.
Metallomics. 2021 Jun 3;13(6). doi: 10.1093/mtomcs/mfab025.
Hemochromatosis is an iron overload disease, which lacks nutritional intervention strategies. This study explored the protective effect of quercetin on hemochromatosis and its possible mechanism through network pharmacology. We used Online Mendelian Inheritance in Man to screen the disease targets of hemochromatosis, and further constructed a potential protein interaction network through STITCH. The above-mentioned targets revealed by Gene enrichment analysis have played a significant role in ferroptosis, mineral absorption, basal cell carcinoma, and related signal pathways. Besides, the drug likeness of quercetin obtained by Comparative Toxicogenomics Database was evaluated by Traditional Chinese Medicine Systems Pharmacology, and potential drug targets identified by PharmMapper and similar compounds identified by PubChem were selected for further research. Moreover, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the relationship between quercetin and glycosylation. Furthermore, we performed experiments to verify that the protective effect of quercetin on iron overload cells is to inhibit the production of reactive oxygen species, limit intracellular iron, and degrade glycosaminoglycans. Finally, iron-induced intracellular iron overload caused ferroptosis, and quercetin and fisetin were potential ferroptosis inhibitors. In conclusion, our study revealed the correlation between hemochromatosis and ferroptosis, provided the relationship between the target of quercetin and glycosylation, and verified that quercetin and its similar compounds interfere with iron overload related disease. Our research may provide novel insights for quercetin and its structurally similar compounds as a potential nutritional supplement for iron overload related diseases.
血色素沉着症是一种铁过载疾病，目前缺乏营养干预策略。本研究通过网络药理学探讨了槲皮素对血色素沉着症的保护作用及其可能机制。我们利用《人类孟德尔遗传在线》筛选血色素沉着症的疾病靶点，并通过STITCH进一步构建潜在的蛋白质相互作用网络。基因富集分析揭示的上述靶点在铁死亡、矿物质吸收、基底细胞癌及相关信号通路中发挥了重要作用。此外，通过中药系统药理学对比较毒理基因组学数据库获得的槲皮素药物相似性进行评估，选择通过PharmMapper鉴定的潜在药物靶点和通过PubChem鉴定的类似化合物进行进一步研究。此外，基因本体论和京都基因与基因组百科全书通路分析揭示了槲皮素与糖基化之间的关系。此外，我们进行实验验证槲皮素对铁过载细胞的保护作用是抑制活性氧的产生、限制细胞内铁并降解糖胺聚糖。最后，铁诱导的细胞内铁过载导致铁死亡，槲皮素和非瑟酮是潜在的铁死亡抑制剂。总之，我们的研究揭示了血色素沉着症与铁死亡之间的相关性，提供了槲皮素靶点与糖基化之间的关系，并验证了槲皮素及其类似化合物可干扰铁过载相关疾病。我们的研究可能为槲皮素及其结构相似化合物作为铁过载相关疾病的潜在营养补充剂提供新的见解。
