背景:口腔黏膜炎是接受放疗或化疗的癌症患者最常见和最麻烦的并发症。最近的研究表明枸杞,一种在中国广泛种植的重要经济作物,在其他几个器官中具有上皮保护作用。然而,目前尚不清楚枸杞是否对口腔黏膜炎有有益作用。网络药理学已被建议应用于“多组分多目标”功能食品研究。目的通过网络药理学评价枸杞对口腔黏膜炎的影响,分子对接和实验验证。
目的:通过网络药理学和分子对接结合实验验证,探讨枸杞治疗口腔黏膜炎的生物学效应和分子机制。
方法:基于网络药理学方法,我们从公共数据库中收集了枸杞的活性成分和相关靶标,以及与口腔粘膜炎相关的目标。我们绘制了蛋白质-蛋白质相互作用(PPI)网络,进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)功能富集,并使用Cytoscape构建了一个“成分-疾病-靶标”网络和“成分-途径-靶标”网络,以进一步分析枸杞抗口腔黏膜炎的内在分子机制。使用分子对接策略进行亲和力和稳定性预测,并进行了实验,以证明枸杞抗口腔黏膜炎的生物学效应和可能的机制。
结果:在49个组件和61个OM目标之间建立了一个网络。主要活性化合物是槲皮素,β-胡萝卜素,巴马汀,和花青素.预测的核心目标是IL-6,RELA,TP53,TNF,IL10,CTNNB1,AKT1,CDKN1A,HIF1A和MYC。富集分析预测治疗效果主要是通过调节炎症,凋亡,缺氧反应与TNF和HIF通路有关。分子对接结果显示关键组分与核心靶标结合良好。在化学和辐射诱导的OM模型中,枸杞明显促进愈合,减轻炎症。实验验证显示枸杞靶向关键基因(IL-6,RELA,TP53,TNF,IL10,CTNNB1,AKT1,CDKN1A,HIF1A,和MYC)通过调节HIF和TNF信号通路,使用RT-qPCR验证,免疫荧光染色和蛋白质印迹分析。
结论:结论:本研究通过网络药理学分析和实验验证,系统论证了枸杞对口腔黏膜炎的可能治疗作用及机制。结果表明,枸杞可通过TNF和HIF信号通路促进愈合,减轻炎症反应。
BACKGROUND: Oral mucositis is the most common and troublesome complication for cancer patients receiving radiotherapy or chemotherapy. Recent research has shown that Lycium barbarum, an important economic crop widely grown in China, has epithelial protective effects in several other organs. However, it is unknown whether or not Lycium barbarum can exert a beneficial effect on oral mucositis. Network pharmacology has been suggested to be applied in \"multi-component-multi-target\" functional food studies. The purpose of this study is to evaluate the effect of Lycium barbarum on oral mucositis through network pharmacology, molecular docking and experimental validation.
OBJECTIVE: To explore the biological effects and molecular mechanisms of Lycium barbarum in the treatment of oral mucositis through network pharmacology and molecular docking combined with experimental validation.
METHODS: Based on network pharmacology methods, we collected the active components and related targets of Lycium barbarum from public databases, as well as the targets related to oral mucositis. We mapped protein- protein interaction (PPI) networks, performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment, and constructed a \'components-disease-targets\' network and \'components- pathways-targets\' network using Cytoscape to further analyse the intrinsic molecular mechanisms of Lycium barbarum against oral mucositis. The affinity and stability predictions were performed using molecular docking strategies, and experiments were conducted to demonstrate the biological effects and possible mechanisms of Lycium barbarum against oral mucositis.
RESULTS: A network was established between 49 components and 61 OM targets. The main active compounds were quercetin, beta-carotene, palmatine, and cyanin. The predicted core targets were IL-6, RELA, TP53, TNF, IL10, CTNNB1, AKT1, CDKN1A, HIF1A and MYC. The enrichment analysis predicted that the therapeutic effect was mainly through the regulation of inflammation, apoptosis, and hypoxia response with the involvement of TNF and HIF pathways. Molecular docking results showed that key components bind well to the core targets. In both chemically and radiation-induced OM models, Lycium barbarum significantly promoted healing and reduced inflammation. The experimental verification showed Lycium barbarum targeted the key genes (IL-6, RELA, TP53, TNF, IL10, CTNNB1, AKT1, CDKN1A, HIF1A, and MYC) through regulating the HIF and TNF signaling pathways, which were validated using the RT-qPCR, immunofluorescence staining and western blotting assays.
CONCLUSIONS: In conclusion, the present study systematically demonstrated the possible therapeutic effects and mechanisms of Lycium barbarum on oral mucositis through network pharmacology analysis and experimental validation. The results showed that Lycium barbarum could promote healing and reduce the inflammatory response through TNF and HIF signaling pathways.