Network Pharmacology-based and Molecular Docking Combined with GEO Gene Chips to Investigate the Potential Mechanism of Duhuo Jisheng Decoction against Rheumatoid Arthritis


Cite item

Full Text

Abstract

Background:Rheumatoid Arthritis (RA) is a chronic autoimmune disease with various symptoms in patients. Duhuo Jisheng Decoction (DHJSD) has been used to treat RA in China for a long history as a classic TCM formula. However, the underlying pharmacological mechanism still needs to be elucidated.

Purpose:In the current study, we combined network pharmacology with molecular docking to investigate the potential mechanism of DHJSD treating RA.

Methods:The active compounds and related targets of DHJSD were obtained from the TCMSP database. The RA targets were retrieved from the GEO database. The PPI network of overlapping targets was constructed, whereas the core genes were selected by CytoNCA for molecular docking. GO and KEGG enrichment analysis were used to further explore the biological process and pathways of overlapping targets. On this basis, molecular docking was carried out to verify the interrelations of the main compounds and core targets.

Results:In this study, we found 81 active components corresponding to 225 targets of DHJSD. Moreover, 775 RA-related targets were obtained, of which 12 were shared between DHJSD targets and RA target genes. From GO and KEGG analysis, there were 346 GO items and 18 signaling pathways. As the molecular docking showed, the binding of components was stable with the core gene.

Conclusion:In conclusion, our works revealed the underlying mechanism of DHJSD for treating RA using network pharmacology and molecular docking, which provided a theoretical basis for further clinical application in the future.

About the authors

Zhao Yang

Department of Orthopedics, Tianjin Hospital

Author for correspondence.
Email: info@benthamscience.net

Zhen-Zhen Yuan

Department of Orthopedics, Tianjin Hospital

Email: info@benthamscience.net

Xin-long Ma

Department of Orthopedics, Tianjin Hospital

Author for correspondence.
Email: info@benthamscience.net

References

  1. Aihaiti, Y.; Song Cai, Y. Tuerhong, X.; Ni Yang, Y.; Ma, Y.; Shi Zheng, H.; Xu, K.; Xu, P. Therapeutic effects of naringin in rheumatoid arthritis: Network pharmacology and experimental validation. Front. Pharmacol., 2021, 12, 672054. doi: 10.3389/fphar.2021.672054 PMID: 34054546
  2. Lin, Y.J.; Anzaghe, M.; Schülke, S. Update on the pathomechanism, diagnosis, and treatment options for rheumatoid arthritis. Cells, 2020, 9(4), 880. doi: 10.3390/cells9040880 PMID: 32260219
  3. Bullock, J.; Rizvi, S.A.A.; Saleh, A.M. Rheumatoid Arthritis: A brief overview of the treatment. Med. Princ. Pract., 2018, 27(6), 501-507.
  4. Liu, Z.; Wang, Z.; Huang, C.; Fu, Z.; Liu, Y.; Wei, Z.; Liu, S.; Ma, C.; Shen, J.; Duan, D.D. Duhuo Jisheng Decoction inhibits SDF-1-induced inflammation and matrix degradation in human degenerative nucleus pulposus cells in vitro through the CXCR4/NF-κB pathway. Acta Pharmacol. Sin., 2018, 39(6), 912-922. doi: 10.1038/aps.2018.36 PMID: 29795361
  5. Xiong, Z.; Zheng, C.; Chang, Y. Exploring the pharmacological mechanism of duhuo jisheng decoction in treating osteoporosis based on network pharmacology. Evid. Based Complement. Alternat. Med., 2021, 2021, 5510290. doi: 10.1155/2021/5510290
  6. Zhao, J.; Zha, Q.; Jiang, M. Expert consensus on the treatment of rheumatoid arthritis with Chinese patent medicines. J. Altern. Complement. Med ., 2013, 19(2), 111-118. doi: 10.1089/acm.2011.0370
  7. Liu, F.; Liu, G.; Liang, W.; Ye, H.; Weng, X.; Lin, P.; Li, H.; Chen, J.; Liu, X.; Li, X. Duhuo Jisheng decoction treatment inhibits the sodium nitroprussiate-induced apoptosis of chondrocytes through the mitochondrial-dependent signaling pathway. Int. J. Mol. Med., 2014, 34(6), 1573-1580. doi: 10.3892/ijmm.2014.1962 PMID: 25339266
  8. Tang, M.; Xie, X.; Yi, P. Integrating network pharmacology with molecular docking to unravel the active compounds and potential mechanism of simiao pill treating rheumatoid arthritis. Evid. Based Complement. Alternat. Med., 2020, 2020, 5786053. doi: 10.1155/2020/5786053
  9. Yan, H-X.; Xu, C-F.; Yang, H. Network pharmacology-based analysis on the curative effect of kunxian capsules against rheumatoid arthritis. Evid. Based Complement. Alternat. Med., 2021, 2021, 6812374. doi: 10.1155/2021/6812374
  10. Basu, A.; Schell, J.; Scofield, R.H. Dietary fruits and arthritis. Food Funct., 2018, 9(1), 70-77. doi: 10.1039/C7FO01435J PMID: 29227497
  11. Guazelli, C.F.S.; Staurengo-Ferrari, L.; Zarpelon, A.C. Quercetin attenuates zymosan-induced arthritis in mice. Biomed. Pharmacother., 2018, 102, 175-184. doi: 10.1016/j.biopha.2018.03.057
  12. Zhang, C.F.; Zhang, S.L.; He, X.; Yang, X.L.; Wu, H.T.; Lin, B.Q.; Jiang, C.P.; Wang, J.; Yu, C.H.; Yang, Z.L.; Wang, C.Z.; Li, P.; Yuan, C.S. Antioxidant effects of Genkwa flos flavonoids on Freund׳s adjuvant-induced rheumatoid arthritis in rats. J. Ethnopharmacol., 2014, 153(3), 793-800. doi: 10.1016/j.jep.2014.03.046 PMID: 24685587
  13. Pan, D.; Li, N.; Liu, Y.; Xu, Q.; Liu, Q.; You, Y.; Wei, Z.; Jiang, Y.; Liu, M.; Guo, T.; Cai, X.; Liu, X.; Wang, Q.; Liu, M.; Lei, X.; Zhang, M.; Zhao, X.; Lin, C. Kaempferol inhibits the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes by blocking activation of the MAPK pathway. Int. Immunopharmacol., 2018, 55, 174-182. doi: 10.1016/j.intimp.2017.12.011 PMID: 29268189
  14. Khandia, R.; Munjal, A.K.; Iqbal, H.M.N.; Dhama, K. Heat shock proteins: Therapeutic perspectives in inflammatory disorders. Recent Pat. Inflamm. Allergy Drug Discov., 2017, 10(2), 94-104. doi: 10.2174/1872213X10666161213163301 PMID: 27978789
  15. White, P.T.; Subramanian, C.; Motiwala, H.F.; Cohen, M.S. Natural withanolides in the treatment of chronic diseases. Adv. Exp. Med. Biol., 2016, 928, 329-373. doi: 10.1007/978-3-319-41334-1_14 PMID: 27671823
  16. Guo, Q.; Mao, X.; Zhang, Y.; Meng, S.; Xi, Y.; Ding, Y.; Zhang, X.; Dai, Y.; Liu, X.; Wang, C.; Li, Y.; Lin, N. Guizhi-Shaoyao-Zhimu decoction attenuates rheumatoid arthritis partially by reversing inflammation-immune system imbalance. J. Transl. Med., 2016, 14(1), 165. doi: 10.1186/s12967-016-0921-x PMID: 27277474
  17. Maruotti, N.; Cantatore, F.P.; Ribatti, D. Putative effects of potentially anti-angiogenic drugs in rheumatic diseases. Eur. J. Clin. Pharmacol., 2014, 70(2), 135-140. doi: 10.1007/s00228-013-1605-6 PMID: 24196651
  18. Jian, C.; Yan, J.; Zhang, H.; Zhu, J. Recent advances of small molecule fluorescent probes for distinguishing monoamine oxidase-A and monoamine oxidase-B in vitro and in vivo. Mol. Cell. Probes, 2021, 55, 101686. doi: 10.1016/j.mcp.2020.101686 PMID: 33279529
  19. Dronjak, S.; Stefanovic, B.; Jovanovic, P.; Spasojevic, N.; Jankovic, M.; Jeremic, I.; Hoffmann, M. Altered cardiac gene expression of noradrenaline enzymes, transporter and β-adrenoceptors in rat model of rheumatoid arthritis. Auton. Neurosci., 2017, 208, 165-169. doi: 10.1016/j.autneu.2017.10.003 PMID: 29029974
  20. Igari, T.; Shimamura, T. Serotonin metabolism and its enzymic activities in joint diseases. Clin. Orthop. Relat. Res., 1979, & NA;(139), 232-249. doi: 10.1097/00003086-197903000-00035 PMID: 455840
  21. Lesniak, A.; Aarnio, M.; Jonsson, A.; Norberg, T.; Nyberg, F.; Gordh, T. High-throughput screening and radioligand binding studies reveal monoamine oxidase-B as the primary binding target for d-deprenyl. Life Sci., 2016, 152, 231-237. doi: 10.1016/j.lfs.2016.03.058 PMID: 27058977
  22. Elhaj Mahmoud, D.; Kaabachi, W.; Sassi, N.; Mokhtar, A.; Ben Ammar, L.; Rekik, S.; Tarhouni, L.; Kallel-Sellami, M.; Cheour, E.; Laadhar, L. Expression of extracellular matrix components and cytokine receptors in human fibrocytes during rheumatoid arthritis. Connect. Tissue Res., 2021, 62(6), 720-731. doi: 10.1080/03008207.2021.1873962 PMID: 33427511
  23. Chakraborty, D.; Gupta, K.; Biswas, S. A mechanistic insight of phytoestrogens used for Rheumatoid arthritis: An evidence-based review. Biomed. Pharmacother., 2021, 133, 111039. doi: 10.1016/j.biopha.2020.111039
  24. Orellana, C.; Saevarsdottir, S.; Klareskog, L.; Karlson, E.W.; Alfredsson, L.; Bengtsson, C. Postmenopausal hormone therapy and the risk of rheumatoid arthritis: Results from the Swedish EIRA population-based case-control study. Eur. J. Epidemiol., 2015, 30(5), 449-457. doi: 10.1007/s10654-015-0004-y PMID: 25762170
  25. Hang, X.; Zhang, Z.; Niu, R.; Wang, C.; Yao, J.; Xu, Y.; Tao, J.; Li, L.; Chen, F. Estrogen protects articular cartilage by downregulating asic1a in rheumatoid arthritis. J. Inflamm. Res., 2021, 14, 843-858. doi: 10.2147/JIR.S295222 PMID: 33737825
  26. Sapir-Koren, R.; Livshits, G. Rheumatoid arthritis onset in postmenopausal women: Does the ACPA seropositive subset result from genetic effects, estrogen deficiency, skewed profile of CD4+ T-cells, and their interactions? Mol. Cell. Endocrinol., 2016, 431, 145-163. doi: 10.1016/j.mce.2016.05.009 PMID: 27178986
  27. Kuwabara, T.; Ishikawa, F.; Kondo, M.; Kakiuchi, T. The role of IL-17 and related cytokines in inflammatory autoimmune diseases. Mediators Inflamm., 2017, 2017, 1-11. doi: 10.1155/2017/3908061 PMID: 28316374
  28. Amin, A.; Sheikh, N.; Mukhtar, M.; Saleem, T.; Akhtar, T.; Fatima, N.; Mehmood, R. Association of interleukin-17 gene polymorphisms with the onset of Rheumatoid Arthritis. Immunobiology, 2021, 226(1), 152045. doi: 10.1016/j.imbio.2020.152045 PMID: 33387966
  29. Schinocca, C.; Rizzo, C.; Fasano, S.; Grasso, G.; La Barbera, L.; Ciccia, F.; Guggino, G. Role of the IL-23/IL-17 pathway in rheumatic diseases: An overview. Front. Immunol., 2021, 12, 637829. doi: 10.3389/fimmu.2021.637829 PMID: 33692806
  30. Kunwar, S.; Dahal, K.; Sharma, S. Anti-IL-17 therapy in treatment of rheumatoid arthritis: A systematic literature review and meta-analysis of randomized controlled trials. Rheumatol. Int., 2016, 36(8), 1065-1075. doi: 10.1007/s00296-016-3480-9 PMID: 27105880
  31. Pi, H.; Zhou, H.; Jin, H.; Ning, Y.; Wang, Y. Abnormal glucose metabolism in rheumatoid arthritis. BioMed Res. Int., 2017, 2017, 9670434. doi: 10.1155/2017/9670434 PMID: 28529957
  32. Tripolino, C.; Ciaffi, J.; Pucino, V.; Ruscitti, P.; van Leeuwen, N.; Borghi, C.; Giacomelli, R.; Meliconi, R.; Ursini, F. Insulin signaling in arthritis. Front. Immunol., 2021, 12, 672519. doi: 10.3389/fimmu.2021.672519 PMID: 33995414
  33. Shahin, D.; Eltoraby, E.; Mesbah, A. Insulin resistance in early untreated rheumatoid arthritis patients. Clin. Biochem., 2010, 43(7-8), 661-665. doi: 10.1016/j.clinbiochem.2010.01.012
  34. Jin, H.; Ning, Y.; Zhou, H.; Wang, Y. IL-6 promotes Islet β -cell dysfunction in rat collagen-induced arthritis. J. Diabetes Res., 2016, 2016, 7592931. doi: 10.1155/2016/7592931 PMID: 27965984
  35. Panfili, E.; Gerli, R.; Grohmann, U.; Pallotta, M.T. Amino acid metabolism in rheumatoid arthritis: Friend or foe? Biomolecules, 2020, 10(9), 1280. doi: 10.3390/biom10091280 PMID: 32899743
  36. He, M.; Harms, A.C.; van Wijk, E.; Wang, M.; Berger, R.; Koval, S.; Hankemeier, T.; van der Greef, J. Role of amino acids in rheumatoid arthritis studied by metabolomics. Int. J. Rheum. Dis., 2019, 22(1), 38-46. doi: 10.1111/1756-185X.13062 PMID: 28328075
  37. Cheung, T.T.; McInnes, I.B. Future therapeutic targets in rheumatoid arthritis? Semin. Immunopathol., 2017, 39(4), 487-500. doi: 10.1007/s00281-017-0623-3 PMID: 28451787
  38. Tang, M.; Gao, X.; Geng, T.; Chen, X.; Wang, J.; Shen, C.; Gao, H.; Qian, M.; Wang, Z.; Cao, L.; Xiao, W. Metabolomics analysis of the therapeutic effects of Qiwei Tongbi oral liquid on rheumatoid arthritis in rats. J. Pharm. Biomed. Anal., 2021, 202, 114166. doi: 10.1016/j.jpba.2021.114166 PMID: 34052551
  39. Kolodziej, L. Systemic metabolism of tryptophan and its catabolites, kynurenine and 3-HAA, in mice with inflammatory arthritis. Gene, 2013, 512(1), 23-27. doi: 10.1016/j.gene.2012.09.122 PMID: 23063938

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2024 Bentham Science Publishers