The Role of Hydroxychloroquine in Treating Refractory Chronic Urticaria: Multi-targets Drug Analysis Strategy through Network Pharmacology

Methods

Potential targets-network of hydroxychloroquine were predicted with biochemical databases. Then the chronic urticaria-related proteins were searched from diseases-associated databases. After taking the intersection of potential targets / disease-related proteins, the protein-protein interaction network was conducted.

Then the overall biological functions of the targets were estimated by Kyoto Encyclopedia of Genes and Genomes Enrichment and Gene Ontology enrichment. Ultimately, these potential targets of hydroxychloroquine were corroborated by docking verification.Results: The 5 targets (histamine H2 receptor, 5-hydroxytryptamine receptor 2A , vitamin D3 receptor, C-C chemokine receptor type 3 and C-X-C chemokine receptor type 3) associated with the network of 906 proteins regulated PI3K-Akt, MAPK, RAS, Chemokine, Rap1 signaling pathway and so forth.

The overall biological functions were focused on the regulation of immune system process, defense response and immune effector process. The chemical bonds such as π-π stacking and hydrogen bond were the main forces between targets and hydroxychloroquine.Conclusions: This study exhibited the molecular targets-network of hydroxychloroquine in treating chronic urticaria. The 5 key targets involving 906 proteins consisted of the multi-targets pharmacological mechanisms of hydroxychloroquine in treating chronic urticaria.

In addition, our work provided a new insight into the evaluation of drugs whose particular mechanism were not well understood in clinical treatment.Keywords: hydroxychloroquine; chronic urticaria; treatment; network pharmacology; multi-targets drug