Ameliorates Oral Mucositis HIF and TNF Pathways: A Network Pharmacology Approach.

BACKGROUND

Oral mucositis is the most common and troublesome complication for cancer patients receiving radiotherapy or chemotherapy. Recent research has shown that , an important economic crop widely grown in China, has epithelial protective effects in several other organs. However, it is unknown whether or not 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 on oral mucositis through network pharmacology, molecular docking and experimental validation.

AIMS

To explore the biological effects and molecular mechanisms of 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 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 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, significantly promoted healing and reduced inflammation. The experimental verification showed 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.

CONCLUSION

In conclusion, the present study systematically demonstrated the possible therapeutic effects and mechanisms of on oral mucositis through network pharmacology analysis and experimental validation. The results showed that could promote healing and reduce the inflammatory response through TNF and HIF signaling pathways.