Network pharmacology and molecular docking analyses of the Wuwei Mingmu formula indicate that IL-10 and IL-6 are critical targets for treating experimental autoimmune uveitis in rats

Xing Liang¹Junkun Zhang²Fang Yuan¹Li Liang³Jie Li^4*Yajian Duan^1*

• ¹Department of Ophthalmology, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, China
• ²Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, Shanxi Province, China
• ³Department of finance, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi Province, China
• ⁴Department of Cardiology, Shanxi Traditional Chinese Medical Hospital, Taiyuan, Shanxi Province, China

Objectives: In this study, we analyzed the use of the Wuwei Mingmu formula (WMF) for treating experimental autoimmune uveitis (EAU) based on a network pharmacology approach. Methods: We obtained an integrated gene set between WMF and EAU using the TCMSP database and GeneCards database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) network analyses were used to elucidate possible therapeutic mechanisms. Moreover, the relationships among the herbal composition, active ingredients, therapeutic targets, and critical cell signaling pathways used to treat EAU were analyzed. Molecular docking was performed to elucidate the patterns of interactions between the active compounds and the targeted proteins. EAU rat models were constructed to examine the therapeutic efficacy of WMF in vivo. Results: An integrated gene set of 30 genes was acquired. The results of the GO and KEGG analyses indicated that WMF could regulate immune responses and vascular functions during EAU treatment. The PPI network and subnetworks confirmed the presence of 15 hub genes. A network pharmacology map was drawn to understand the complex relationships among herbs, active compounds, targets, and signaling pathways. Additionally, molecular docking was performed on genes with the highest significance (IL-10 and IL-6), representing T-helper activation in immune-mediated uveitis. The active compounds of WMF rapidly docked with IL-10 and IL-6 in the grid box. The results of the in vivo assays revealed that WMF treatment significantly attenuated the pathological changes in EAU rat eyes and alleviated the inflammatory response. Moreover, the increase in the level of IL-6 in EAU rats decreased after WMT stimulation, whereas the IL-10 levels increased in EAU rats after WMF treatment. Conclusions: WMF can be used to treat EAU as it can modulate immune responses and vascular functions. IL-10 and IL-6 are the main therapeutic targets of WMF, and the herbal composition of WMF can be further optimized to increase its therapeutic efficacy.