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Effects of Naringenin on Inflammation in Complete Freund’s Adjuvant-Induced Arthritis by Regulating Bax/Bcl-2 Balance

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Abstract

Naringin (COG) is a flavanone with various bioactivities including an expectorant effect, antitussive effect, and inhibitory effect on asthma and acute lung injury. The aims of the present study were to investigate the antiarthritis activities of COG and elucidate the underlying mechanisms with regard to its molecular basis of action for the best combination. Arthritis was induced by intradermal injection of complete Freund’s adjuvant. Sprague–Dawley rats were randomly divided into five groups with 10 rats in each group: (1) control group, (2) AA group, (3) AA + dexamethasone (AA + Dex, 2 mg/kg), (4) AA + COG (20 mg/kg), (5) AA + COG (40 mg/kg). Paw swelling was measured, and the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 was detected by enzyme-linked immunosorbent assay (ELISA) in serum. Pathological changes of joints tissues were observed by hematoxylin and eosin (HE) staining. Apoptosis of synovial tissues was measured by terminal dUTP nick-end labeling (TUNEL) assay. The expressions of apoptosis-related molecules, including Bcl-2 and Bax, were determined by Western blotting. In both COG and Dex treatments, COG and Dex significantly suppressed paw swelling in AA rats. Moreover, COG and Dex significantly suppressed the production of TNF-α, IL-1β, and IL-6 in serum. HE staining study demonstrated that COG and Dex significantly suppressed pathological changes of joints tissues; TUNEL assay demonstrated that COG and Dex induced apoptosis of AA via regulation of the protein expression of Bcl-2 and Bax. These data suggest that COG may have therapeutic potential for RA.

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References

  1. Feldmann, M., F.M. Brennan, and R.N. Maini. 1996. Role of cytokines in rheumatoid arthritis. Annual Review of Immunology 14: 397–440.

    Article  CAS  PubMed  Google Scholar 

  2. Henderson, B., and E.R. Pettipher. 1985. The synovial lining cell: biology and pathobiology. Seminars in Arthritis and Rheumatism 15: 1–32.

    Article  CAS  PubMed  Google Scholar 

  3. Zvaifler, N.J. 2006. Relevance of the stroma and epithelial-mesenchymal transition (EMT) for the rheumatic diseases. Arthritis Research and Therapy 8: 210.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Baier, A., I. Meineckel, S. Gay, and T. Pap. 2003. Apoptosis in rheumatoid arthritis. Current Opinion in Rheumatology 15: 274–9.

    Article  CAS  PubMed  Google Scholar 

  5. Farahat, M.N., G. Yanni, R. Poston, and G.S. Panayi. 1993. Cytokine expression in synovial membranes of patients with rheumatoid arthritis and osteoarthritis. Annals of the Rheumatic Diseases 52: 870–875.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Singh, S., V. Nair, and Y.K. Gupta. 2011. Antiarthritic activity of majoon suranjan (a polyherbal Unani formulation) in rat. Indian Journal of Medical Research 134: 384–388.

    PubMed Central  PubMed  Google Scholar 

  7. Coelho, M.G., P.A. Reis, V.B. Gava, P.R. Marques, C.R. Gayer, G.A. Laranja, I. Felzenswalb, and K.C. Sabino. 2004. Anti-arthritic effect and subacute toxicological evaluation of Baccharis genistelloidesaqueous extract. Toxicology Letters 154: 69–80.

    Article  CAS  PubMed  Google Scholar 

  8. Le Goff, B., E. Soltner, C. Charrier, Y. Maugars, F. Rédini, D. Heymann, et al. 2009. A combination of methotrexate and zoledronic acid prevents bone erosions and systemic bone mass loss in collagen induced arthritis. Arthritis Research & Therapy 11: R185.

    Article  Google Scholar 

  9. Majithia, V., and S.A. Geraci. 2007. Rheumatoid arthritis: diagnosis and management. American Journal of Medicine 120: 936–939.

    Article  PubMed  Google Scholar 

  10. Feldmann, M., F. Brennan, J. Bondeson, E. Paleolog, B. Foxwell, and R. Maini. 2001. Analysis of cytokine expression in rheumatoid synovium has provided new insights into the pathogenesis of rheumatoid arthritis and new therapeutic opportunities. Transplantation Proceedings 33: 2085–2086.

    Article  CAS  PubMed  Google Scholar 

  11. Liu, M., W. Mao, H. Guan, L. Li, B. Wei, and P. Li. 2011. Effects of taurochenodeoxycholic acid on adjuvant arthritis in rats. International Immunopharmacology 11: 2150–2158.

    Article  CAS  PubMed  Google Scholar 

  12. Refaat, R., M. Salama, E. Abdel Meguid, A. El Sarha, and M. Gowayed. 2013. Evaluation of the effect of losartan and methotrexate combined therapy in adjuvant-induced arthritis in rats. European Journal of Pharmacology 698: 421–428.

    Article  CAS  PubMed  Google Scholar 

  13. Tang, B., Y. Zhang, R. Liang, P. Yuan, J. Du, H. Wang, and L. Wang. 2011. Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway. International Journal of Molecular Medicine 28: 1077–1085.

    CAS  PubMed  Google Scholar 

  14. Mattson, M.P., and G. Kroemer. 2003. Mitochondria in cell death: novel targets for neuroprotection and cardioprotection. Trends in Molecular Medicine 9: 196–205.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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Correspondence to Tianhua Yan.

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Lingpeng zhu, Jing Wang, and Tingting Wei contributed equally to this work.

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zhu, L., Wang, J., Wei, T. et al. Effects of Naringenin on Inflammation in Complete Freund’s Adjuvant-Induced Arthritis by Regulating Bax/Bcl-2 Balance. Inflammation 38, 245–251 (2015). https://doi.org/10.1007/s10753-014-0027-7

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