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Journal of Orthopaedic Surgery and Research
Published in: Journal of Orthopaedic Surgery and Research 1/2023

Open Access 01-12-2023 | Rheumatoid Arthritis | Research article

Network pharmacology and experimental validation methods to reveal the active compounds and hub targets of Curculigo orchioides Gaertn in rheumatoid arthritis

Authors: Xia Liu, Mingchun Huang, Lijuan Wang, Jie Li, Weihui Wu, Qin Wang

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2023

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Abstract

Background

Rheumatoid arthritis (RA) is an autoimmune disease that can lead to joint destruction and deformity. Curculigo orchioides Gaertn (CO) was previously revealed to play a significant role in RA treatment. However, the main active ingredients and molecular mechanisms of CO in regulating RA are still unclear.

Methods

The active ingredients of CO were obtained from the Traditional Chinese Medicine Systems Pharmacology database and published literature. The targets corresponding to these compounds and the targets linked to RA were collected from public databases. The “ingredient-target” and “protein–protein interaction” networks were constructed to screen the main active ingredients and hub targets of CO in the treatment of RA. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment assays were used to elucidate the potential pharmacological mechanism of CO in RA. Molecular docking was performed to detect the binding between the main active ingredients and hub targets. Collagen-induced arthritis rats were used to validate the hub targets of CO against RA.

Results

Network pharmacological topology analysis showed that caffeine, 2,4-dichloro-5-methoxy-3-methylphenol, curculigoside, orcinol glucoside, and orcin were the main active ingredients of CO, and matrix metalloproteinase 9 (MMP9), transcription factor AP-1 (JUN), prostaglandin-endoperoxide synthase 2 (PTGS2), brain-derived neurotrophic factor, and receptor-type tyrosine-protein phosphatase C were the hub targets of CO for RA treatment. Molecular docking revealed that curculigoside and orcinol glucoside had effective binding potential with MMP9, JUN, and PTGS2, respectively. In vivo experiments demonstrated that CO alleviated RA symptoms and inhibited the expression of MMP9, JUN, and PTGS2 proteins.

Conclusions

Our study demonstrates the main active ingredients and potential targets of CO against RA, laying an experimental foundation for the development and application of CO as an anti-RA drug.
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Metadata
Title
Network pharmacology and experimental validation methods to reveal the active compounds and hub targets of Curculigo orchioides Gaertn in rheumatoid arthritis
Authors
Xia Liu
Mingchun Huang
Lijuan Wang
Jie Li
Weihui Wu
Qin Wang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2023
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-023-04352-w

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