EXPLORING THE PHARMACOLOGICAL MECHANISM OF NARINGENIN AND ITS DERIVATIVES AGAINST RHEUMATOID ARTHRITIS USING NETWORK PHARMACOLOGY AND MOLECULAR DOCKING TECHNIQUES
DOI:
https://doi.org/10.22159/ijms.2023.v11i2.47144Keywords:
rheumatoid arthritis, Naringenin, autoimmune, molecular docking, network pharmacologyAbstract
Objective: Flavonoids like Naringenin (NR), which have potent anti-inflammatory effects, are crucial in the treatment of rheumatoid arthritis (RA). Using network pharmacology and molecular docking, this study investigates the potential pharmacological mechanism of NR and its derivatives in the treatment of RA.
Methods: The current study’s purpose was to employ computational methodologies to evaluate the efficiency of several NR phytochemicals against RA. The Indian medicinal plants, Phytochemistry and therapeutics and DrugBank database is used to retrieve potential ligands. While, known target proteins associated with RA were retrieved through the GeneCards database and predicted target proteins related to NR were screened through the STITCH database. STRING database was used to construct a protein-protein interaction network. Gene ontology and Kyoto Encyclopaedia of Genes and Genomes pathway enrichment involved in targets were performed by the ShinyGo 0.76.3 database. The BIOVIA Discovery Studio Visualizer and the virtual screening tool PyRx were used to systematically perform molecular docking. To assess their compatibility with the RA, the top 6 phytocompounds from NR were selected. The pharmacological evaluation of the ligands was carried out using ADMET filters.
Results: The phytocompounds 4’-Hydroxyflavanone and Sakuranetin from the NR derivatives were discovered to be the most potent antagonistic for the protein tumor protein P53 and interleukin-10 protein.
Conclusion: Ligands 4’-Hydroxyflavanone and Sakuranetin are deserving candidates for the suppression of inflammation of RA due to their strong affinity for the protein.
References
Kabra A, Garg R, Brimson J, Živković J, Almawash S, Ayaz M, et al. Mechanistic insights into the role of plant polyphenols and their nano-formulations in the management of depression. Front Pharmacol 2022;13:1046599.
Duda-Madej A, Stecko J, Sobieraj J, Szymańska N, Kozłowska J. Naringenin and its derivatives-health-promoting phytobiotic against resistant bacteria and fungi in humans. Antibiotics 2022;11:1628.
Salehi B, Fokou PV, Sharifi-Rad M, Zucca P, Pezzani R, Martins N, et al. The therapeutic potential of naringenin: A review of clinical trials. Pharmaceuticals (Basel) 2019;12:11.
Ionescu CE, Popescu CC, Agache M, Dinache G, Codreanu C. Depression in Rheumatoid arthritis: A narrative review-diagnostic challenges, pathogenic mechanisms and effects. Medicina (Kaunas) 2022;58:1637.
Smesam HN, Qazmooz HA, Khayoon SQ, Almulla AF, Al-Hakeim HK, Maes M. Pathway phenotypes underpinning depression, anxiety, and chronic fatigue symptoms due to acute rheumatoid arthritis: A precision nomothetic psychiatry analysis. J Pers Med 2022;12:476.
Scherer HU, Häupl T, Burmester GR. The etiology of rheumatoid arthritis. J Autoimmun 2020;110:102400.
Slagter L, Demyttenaere K, Verschueren P, De Cock D. The effect of meditation, mindfulness, and yoga in patients with rheumatoid arthritis. J Pers Med 2022;12:1905.
Metsios GS, Kitas GD. Physical activity, exercise and rheumatoid arthritis: Effectiveness, mechanisms and implementation. Best Pract Res Clin Rheumatol 2018;32:669-82.
Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: A review. JAMA 2018;320:1360-72.
Prasad P, Verma S, Surbhi, Ganguly NK, Chaturvedi V, Mittal SA. Rheumatoid arthritis: Advances in treatment strategies. Mol Cell Biochem 2022; 478:1-20.
Ma C, Wang J, Hong F, Yang S. Mitochondrial dysfunction in rheumatoid arthritis. Biomolecules 2022;12:1216.
Radu AF, Bungau SG. Management of rheumatoid arthritis: An overview. Cells 2021;10:2857.
Tanase DM, Gosav EM, Petrov D, Teodorescu DS, Buliga-Finis ON, Ouatu A, et al. MicroRNAs (miRNAs) in cardiovascular complications of rheumatoid arthritis (RA): What is new? Int J Mol Sci 2022;23:5254.
Yang G, Kang HC, Cho YY, Lee HS, Lee JY. Inflammasomes and their roles in arthritic disease pathogenesis. Front Mol Biosci 2022;9:1027917.
Inciarte-Mundo J, Frade-Sosa B, Sanmartí R. From bench to bedside: Calprotectin (S100A8/S100A9) as a biomarker in rheumatoid arthritis. Front Immunol 2022;13:1001025.
Mueller AL, Payandeh Z, Mohammadkhani N, Mubarak SM, Zakeri A, Bahrami AA, et al. Recent advances in understanding the pathogenesis of rheumatoid arthritis: New treatment strategies. Cells 2021;10:3017.
Zhu Y, Zhao T, Liu M, Wang S, Liu S, Yang Y, et al. Rheumatoid arthritis microenvironment insights into treatment effect of nanomaterials. Nano Today 2022;42:101358.
Huang J, Fu X, Chen X, Li Z, Huang Y, Liang C. Promising therapeutic targets for treatment of rheumatoid arthritis. Front Immunol 2021;12:686155.
Kang R, Kroemer G, Tang D. The tumor suppressor protein p53 and the ferroptosis network. Free Radic Biol Med 2019;133:162-8.
Saraiva M, Vieira P, O’Garra A. Biology and therapeutic potential of interleukin-10. J Exp Med 2020;217:e20190418.
Tang R. Improved dynamic PPI network construction and application of data mining in computer artificial intelligence systems. Sci Programming 2022;2022:2729401.
Muhammed MT, Aki-Yalcin E. Homology modeling in drug discovery: Overview, current applications, and future perspectives. Chem Biol Drug Des 2019;93:12-20.
Pinzi L, Rastelli G. Molecular docking: Shifting paradigms in drug discovery. Int J Mol Sci 2019;20:4331.
Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, et al. SWISS-MODEL: Homology modelling of protein structures and complexes. Nucleic Acids Res 2018;46:W296-303.
Lim YY, Zaidi AM, Miskon A. Composing on-program triggers and on-demand stimuli into biosensor drug carriers in drug delivery systems for programmable arthritis therapy. Pharmaceuticals (Basel) 2022;15:1330.
Zeng W, Jin L, Zhang F, Zhang C, Liang W. Naringenin as a potential immunomodulator in therapeutics. Pharmacol Res 2018;135:122-6.
Arafah A, Rehman MU, Mir TM, Wali AF, Ali R, Qamar W, et al. Multi-therapeutic potential of naringenin (4’,5,7-Trihydroxyflavonone): Experimental evidence and mechanisms. Plants (Basel) 2020;9:1784.
Taghadosi M, Adib M, Jamshidi A, Mahmoudi M, Farhadi E. The p53 status in rheumatoid arthritis with focus on fibroblast-like synoviocytes. Immunol Res 2021;69:225-38.
Hernández-Bello J, Oregón-Romero E, Vázquez-Villamar M, García- Arellano S, Valle Y, Padilla-Gutiérrez JR, et al. Aberrant expression of interleukin-10 in rheumatoid arthritis: Relationship with IL10 haplotypes and autoantibodies. Cytokine 2017;95:88-96.
Cruz MP, Andrade CM, Silva KO, de Souza EP, Yatsuda R, Marques LM, et al. Antinoceptive and anti-inflammatory activities of the ethanolic extract, fractions and flavones isolated from Mimosa tenuiflora (Willd.) Poir (Leguminosae). PLoS One 2016;11:e0150839
Published
How to Cite
Issue
Section
Copyright (c) 2023 SAMEER SHARMA
This work is licensed under a Creative Commons Attribution 4.0 International License.
