Lycium barbarum Ameliorates Oral Mucositis via HIF and TNF Pathways: A Network Pharmacology Approach

Title:Lycium barbarum Ameliorates Oral Mucositis via HIF and TNF Pathways: A Network Pharmacology Approach

Volume: 30

Author(s): Xun Chen, Yanhui Wu, Jing Li, Sijing Jiang, Qiang Sun, Li Xiao, Xiliang Jiang, Xun Xiao, Xianxian Li and Yandong Mu*

Affiliation:

• School of Stomatology, Southwest Medical University, Luzhou 646699, China
• Stomatology Department, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China

Abstract: 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.

Aim: 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.

Conclusion: 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.

Cite this article as:

Chen Xun, Wu Yanhui, Li Jing, Jiang Sijing, Sun Qiang, Xiao Li, Jiang Xiliang, Xiao Xun, Li Xianxian and Mu Yandong*, Lycium barbarum Ameliorates Oral Mucositis via HIF and TNF Pathways: A Network Pharmacology Approach, Current Pharmaceutical Design 2024; 30 () . https://dx.doi.org/10.2174/0113816128312694240712072959

DOI https://dx.doi.org/10.2174/0113816128312694240712072959	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286