The multi-targets mechanism of hydroxychloroquine in the treatment of systemic lupus erythematosus based on network pharmacology

Abstract

Background Network pharmacology is used with bioinformatic tools to broaden the understanding of drugs’ potential targets and the intersections with key genes of particular disease. Here we applied network pharmacology to collect testable hypotheses about the multi-targets mechanism of hydroxychloroquine (HCQ) against systemic lupus erythematosus (SLE). Methods Firstly, we predicted the potential targets of HCQ. Secondly, we got the related genes of SLE returned from databases. Thirdly, the intersections of the potential targets (HCQ) and related genes (SLE) were analyzed with gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, we validated our predictions of the potential targets by performing docking studies with HCQ. Results The results suggest that the efficacy of HCQ against SLE is mainly associated with the targets of cyclin-dependent kinase 2 (CDK2), estrogen receptor alpha (ESR1) and CDK1, which regulate PI3K/Akt/GSK3β as well as interferon (IFN) signaling pathway. Biological process of the network associated with the three targets is concentrated in the inhibition of immune response, negative regulation of gene expression and regulation of immune system process. Molecular docking analysis proves that hydrogen bonding and π-π stacking are the main forms of interaction. Conclusions Our research provides protein targets affected by HCQ in the treatment of SLE. Three key targets (CDK2, ESR1 and CDK1) involving 1766 proteins become the multi-targets mechanism of HCQ in the treatment of SLE. As well, the research also provides a new idea for introducing network pharmacology into the evaluation of the drugs with multi-targets in dermatology.

Targets Exploration of Hydroxychloroquine for Pigmentation and Cell Protection Effect in Melanocytes: The Clue for Vitiligo Treatment

“…The top 100 potential targets were selected according to the calculated parameters. 24 , 25 Vitiligo-related proteins were searched using the keywords and species (“vitiligo” and “Homo sapiens”) across four databases, including Genecards ( https://www.genecards.org/ ), OMIM ( https://omim.org/ ), Drugbank ( https://go.drugbank.com/ ) and DisGeNET ( https://www.disgenet.org/ ). A total of 1185 vitiligo-related proteins were screened.…”

The multi‐target mechanism of Cyclosporin A in the treatment of vitiligo based on network pharmacology

“…Some single-component chemical drugs may act on multiple different types of targets such as protein receptors, ion channels, transmembrane signaling molecules and enzymes. 7 The interactions between the targets of drug are complicated. The pathogenesis of some disease is complex, with molecular network mechanism.…”

“…Network pharmacology is a new discipline based on the theory of systems biology, which could be used to analyze the network of biological systems and select specific signal nodes for multi‐target drug molecular design. Some single‐component chemical drugs may act on multiple different types of targets such as protein receptors, ion channels, transmembrane signaling molecules and enzymes 7 . The interactions between the targets of drug are complicated.…”

Systematic Understanding of Anti-Aging Effect of Coenzyme Q10 on Oocyte Through a Network Pharmacology Approach

“…Currently, although anti-oocyte aging activities exerted by CoQ10 have been reported, details of biomarkers and the biological pathways through which CoQ10 counteracts oocyte aging are limited. In previous studies, a network pharmacologybased approach was successfully used to reveal all candidate targets, functions, and potential therapeutic mechanisms of drugs (20)(21)(22). In the present study, system network pharmacology combined with molecular docking was performed to reveal the potential targets and therapeutic mechanisms of CoQ10 against oocyte aging.…”