The molecular basis of all-trans retinoic acid binding to the target genes involved in rheumatoid arthritis through network pharmacology and molecular docking

Xi Zheng; Xin Ke; Jie Gao; Zhaohui Zheng; Ping Zhu

doi:10.1007/s10067-025-07482-0

The molecular basis of all-trans retinoic acid binding to the target genes involved in rheumatoid arthritis through network pharmacology and molecular docking

Clin Rheumatol. 2025 May 17. doi: 10.1007/s10067-025-07482-0. Online ahead of print.

Authors

Xi Zheng¹, Xin Ke¹, Jie Gao¹, Zhaohui Zheng², Ping Zhu³

Affiliations

¹ Department of Clinical Immunology of Xijing Hospital, Department of Cell Biology of National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, 710032, China.
² Department of Clinical Immunology of Xijing Hospital, Department of Cell Biology of National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, 710032, China. zhengzh@fmmu.edu.cn.
³ Department of Clinical Immunology of Xijing Hospital, Department of Cell Biology of National Translational Science Center for Molecular Medicine, Fourth Military Medical University, Xi'an, 710032, China. zhuping@fmmu.edu.cn.

PMID: 40379851
DOI: 10.1007/s10067-025-07482-0

Abstract

Objective: All-trans retinoic acid (ATRA), a natural derivative of Vitamin A, plays a crucial role in cellular proliferation, differentiation, and metabolic functions. It has been reported to possess significant antioxidant and anti-inflammatory properties. However, a comprehensive investigation into its potential mechanisms within the framework of rheumatoid arthritis (RA) has yet to be adequately addressed.

Methods: This study aimed to identify potential targets of ATRA by employing databases such as DrugBank and SwissTargetPrediction. Furthermore, disease-associated genes relevant to rheumatoid arthritis were sourced from DisGeNET and GeneCards. Analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were conducted. Drug-target-pathway networks were developed, and significant hub genes were identified. In addition, molecular docking studies were performed to assess the binding affinity of ATRA.

Results: The results indicated that ATRA engages with 127 identified target genes, of which 85 are linked to rheumatoid arthritis (RA). Analyses employing Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and network approaches suggested that these targets participate in inflammatory pathways and metabolic processes pertinent to RA. Additionally, molecular docking studies revealed a significant binding affinity between ATRA and the proteins CYP1A1 and CYP2B6.

Conclusion: ATRA is anticipated to engage with various proteins and pathways associated with rheumatoid arthritis, suggesting its potential utility in the clinical management of this disorder. Key Points • All-trans retinoic acid (ATRA) has been shown to interact with 85 specific genes in patients with RA, among which 10 key hub genes have been identified. • Molecular docking studies indicate that ATRA exhibits the lowest binding affinity with the genes CYP1 A1 and CYP2B6.

Keywords: All-trans retinoic acid; Molecular docking; Network pharmacology; Rheumatoid arthritis.