ReferenceID 5839
Therapeutic Effects of Naringin in Rheumatoid Arthritis: Network Pharmacology and Experimental Validation
Front Pharmacol
Rheumatoid arthritis is a chronic autoimmune disease characterized by persistent hyperplasia of the synovial membrane and progressive erosion of articular cartilage. Disequilibrium between the proliferation and death of
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Record Fields
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- Reference Id
- 5839
- Evidence Id
- 22429
- Core Evidence Id
- 22429
- Source Reference Id
- 4932
- Herb2 Reference Id
- HBREF005729
- Subject Paper Key
- HBIN036380_34054546
- Pubmed Id
- 34054546
- Doi
- 10.3389/fphar.2021.672054
- Paper Title
- Therapeutic Effects of Naringin in Rheumatoid Arthritis: Network Pharmacology and Experimental Validation
- Paper Abstract
- Rheumatoid arthritis is a chronic autoimmune disease characterized by persistent hyperplasia of the synovial membrane and progressive erosion of articular cartilage. Disequilibrium between the proliferation and death of RA fibroblast-like synoviocytes (RA-FLSs) is the critical factor in progression of RA. Naringin has been reported to exert anti-inflammatory and antioxidant effect in acute and chronic animal models of RA. However, the therapeutic effect and underlying mechanisms of naringin in human RA-FLS remain unclear. Based on network pharmacology, the corresponding targets of naringin were identified using SwissTargetPrediction database, STITCH database, and Comparative Toxicogenomics Database. Deferentially expressed genes (DEGs) in RA were obtained from the GEO database. The protein-protein interaction (PPI) networks of intersected targets were constructed using the STRING database and visualized using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and the pathways directly related to pathogenesis of RA were integrated manually. Further, in vitro studies were carried out based on network pharmacology. 99 target genes were intersected between targets of naringin and DEGs. The PPI network and topological analysis indicated that IL-6, MAPK8, MMP-9, TNF, and MAPK1 shared the highest centrality among all. GO analysis and KEGG analysis indicated that target genes were mostly enriched in (hsa05200) pathways in cancer, (hsa05161) hepatitis B, (hsa04380) osteoclast differentiation, (hsa04151) PI3K-Akt signaling pathway, and (hsa05142) Chagas disease (American trypanosomiasis). In vitro studies revealed that naringin exposure was found to promote apoptosis of RA-FLS, increased the activation of caspase-3, and increased the ratio of Bax/Bcl-2 in a dose-dependent manner. Furthermore, treatment of naringin attenuated the production of inflammatory cytokines and matrix metalloproteinases (MMPs) in TNF-alpha-induced RA-FLS. Moreover, treatment of naringin inhibited the phosphorylation of Akt and ERK in RA-FLS. Network pharmacology provides a predicative strategy to investigate the therapeutic effects and mechanisms of herbs and compounds. Naringin inhibits inflammation and MMPs production and promotes apoptosis in RA-FLS via PI3K/Akt and MAPK/ERK signaling pathways.
- Journal
- Front Pharmacol
- Publish Year
- 2021
- Experiment Subject
- human
- Experiment Type
- Others
- Phenotype Related
- Erosion Of Articular Cartilage; Hyperplasia Of The Synovial Membrane; Chronic Autoimmune Disease; Rheumatoid Arthritis; Cancer; Trypanosomiasis; Chagas Disease
- Paper Title Cn
- Paper Title En
- Therapeutic Effects of Naringin in Rheumatoid Arthritis: Network Pharmacology and Experimental Validation
- Bilingual Status
- semi_complete