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. 2025;31(9):730-740.
doi: 10.2174/0113816128347345241028063515.

Network Pharmacological Analysis of Hydroxychloroquine Intervention in the Treatment of Iga Nephropathy

Mengxiao Zou  1 , Gang Xu  1 , Shuwang Ge  1 , Kanglin Guo  1 , Qian Duo  1 , Yichun Cheng  1
Affiliations

Network Pharmacological Analysis of Hydroxychloroquine Intervention in the Treatment of Iga Nephropathy

Mengxiao Zou et al. Curr Pharm Des. 2025.

Abstract

Background: IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally and has a high propensity to develop into end-stage renal disease (ESRD). Hydroxychloroquine has been proven to reduce proteinuria in IgAN patients, but the precise mechanism remains unclear. Therefore, network pharmacology was used to investigate the mechanism.

Methods: PubChem and SwissADME databases were utilized to acquire the structure of hydroxychloroquine. The SwissTargetPrediction, PharmMapper, DrugBank, TargetNet, and BATMAN-TCM databases were then utilized to obtain the targets. The target genes related to IgAN were then gathered from the databases, which included GeneCards, PHARMGKB, DrugBank, OMIM, and DisGeNET. Common targets were obtained by UniProt. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to define the main molecular mechanisms and pathways. Furthermore, a protein-protein interaction (PPI) network was constructed using the STRING tool, and the core targets were obtained by Cytoscape. Finally, molecular docking between the core targets and hydroxychloroquine was performed.

Results: 167 common target genes were acquired by overlapping. The core targets were TNF, ALB, IL1B, JUN, FOS, SRC, and MMP9. The GO and KEGG results showed the targets to be related to the production of inflammatory cytokines and chemokines and were engaged in the toll-like receptor (TLR) signaling pathway. At the same time, the molecular docking results showed that the core targets all combined with hydroxychloroquine closely.

Conclusion: This study proved that hydroxychloroquine may treat IgAN through the TLR signaling pathway, and the restraint of TNF, TLR, IL1B, and JUN may be essential for the treatment.

Keywords: Hydroxychloroquine; IgA nephropathy; end-stage renal disease.; network pharmacology; signaling pathway; toll-like receptor.

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Conflict of interest statement

The authors declare no conflict of interest, financial or otherwise.

Figures

Fig. (1)
Fig. (1)
(A) Common targets of hydroxychloroquine and IgAN; (B) PPI network and core network.
Fig. (2)
Fig. (2)
(A) Biological processes of GO analysis; (B) Molecular functions of GO analysis; (C) Cell components of GO analysis; (D) KEGG pathway enrichment analysis.
Fig. (3)
Fig. (3)
(A) Hydroxychloroquine bound to IL1B; (B) Hydroxychloroquine bound to JUN; (C) Hydroxychloroquine bound to TLR2; (D) Hydroxychloroquine bound to TLR3; (E) Hydroxychloroquine bound to TLR4; (F) Hydroxychloroquine bound to TNF.
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