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Paeoniflorin, the Main Monomer Component of Paeonia lactiflora, Exhibits Anti-inflammatory Properties in Osteoarthritis Synovial Inflammation

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Abstract

Objective

To explore the mechanism of paeoniflorin (PF) on osteoarthritis (OA) synovial inflammation from network pharmacology to experimental pharmacology.

Methods

Targets of OA were constructed by detecting the database of network database platforms (Therapeutic Target database, DrugBank and GeneCards), and the targets of PF were constructed by PubChem and Herbal Ingredients’ Targets database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these co-targeted genes were conducted via Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, and protein-protein interaction (PPI) networks were conducted via the search tool for the retrieval of interacting genes (STRING) database. Cell counting kit-8 (CCK-8) assay was performed to assess the potential toxicity of PF on human OA fibroblast-like synoviocytes (FLS), quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA) and Western blot were used to verify the potential mechanism of PF in synovial inflammation.

Results

Twenty-six co-targeted genes were identified. GO enrichment results showed that these co-targeted genes were most likely localized in the cytoplasm, and the biological processes mainly involved ‘cellular response to hypoxia’ ‘lipopolysaccharide (LPS)-mediated signaling pathway’ and ‘positive regulation of gene expression’. KEGG pathway analysis indicated that these co-targeted genes may function through pathways associated with ‘hypoxia-inducible factor-1 (HIF-1) signaling pathway’ and ‘tumor-necrosis factor (TNF) signaling pathway’. The PPI network showed that the top 3 hub genes were TP53, TNF, and CASP3. Molecular docking results showed that PF was well docking with TNF. CCK-8 showed no potential toxicity of 10, 20 and 50 µmol/L PF on human OA FLS. And PF significantly decreased the expression levels of interleukin-1 β, interleukin-6, TNF-α matrix metalloproteinase 13 (MMP13), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and TNF-α in LPS-induced OA FLS.

Conclusion

PF exhibited potent anti-inflammatory effect in OA synovial inflammation.

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Authors and Affiliations

Authors

Contributions

Wang QF contributed to the conception of the study; Chen P, Ruan AM, Zhou J and MA YF conducted the experiment; Chen P wrote the manuscript; Chen P and Zhou J analyzed the data. All author read the paper and approved the final version for publication.

Corresponding author

Correspondence to Qing-fu Wang.

Ethics declarations

The authors declare that they have no conflict of interest.

Additional information

Supported by the National Natural Science Foundation of China (No. 81373662 and No. 81874475), Capacity Building Project of Chinese and Western Medicine Clinical Collaboration on Major Difficult Disease (No. 201803190106)

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Chen, P., Zhou, J., Ruan, Am. et al. Paeoniflorin, the Main Monomer Component of Paeonia lactiflora, Exhibits Anti-inflammatory Properties in Osteoarthritis Synovial Inflammation. Chin. J. Integr. Med. 30, 433–442 (2024). https://doi.org/10.1007/s11655-023-3653-9

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