Skip to main content
SpringerLink
Log in

Bergenin Plays an Anti-Inflammatory Role via the Modulation of MAPK and NF-κB Signaling Pathways in a Mouse Model of LPS-Induced Mastitis

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Mastitis is a major disease in humans and other animals and is characterized by mammary gland inflammation. It is a major disease of the dairy industry. Bergenin is an active constituent of the plants of genus Bergenia. Research indicates that bergenin has multiple biological activities, including anti-inflammatory and immunomodulatory properties. The objective of this study was to evaluate the protective effects and mechanism of bergenin on the mammary glands during lipopolysaccharide (LPS)-induced mastitis. In this study, mice were treated with LPS to induce mammary gland mastitis as a model for the disease. Bergenin treatment was initiated after LPS stimulation for 24 h. The results indicated that bergenin attenuated inflammatory cell infiltration and decreased the concentration of NO, TNF-α, IL-1β, and IL-6, which were increased in LPS-induced mouse mastitis. Furthermore, bergenin downregulated the phosphorylation of nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPK) signaling pathway proteins in mammary glands with mastitis. In conclusion, bergenin reduced the expression of NO, TNF-α, IL-1β, and IL-6 proinflammatory cytokines by inhibiting the activation of the NF-κB and MAPKs signaling pathways, and it may represent a novel treatment strategy for mastitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Viguier, C., S. Arora, N. Gilmartin, K. Welbeck, and R. O’Kennedy. 2009. Mastitis detection: current trends and future perspectives. Trends in Biotechnology 27: 486–493.

    Article  PubMed  CAS  Google Scholar 

  2. Melchior, M.B., H. Vaarkamp, and J. Fink-Gremmels. 2006. Biofilms: a role in recurrent mastitis infections? Veterinary Journal 171: 398–407.

    Article  CAS  Google Scholar 

  3. Carneiro, D.M.V.F., P.F. Domingues, and A.K. Vaz. 2009. Innate immunity of the bovine mammary gland: response to infection. Ciencia Rural 39: 1934–1943.

    Article  CAS  Google Scholar 

  4. Bradley, A.J. 2002. Bovine mastitis: an evolving disease. Veterinary Journal 164: 116–128.

    Article  CAS  Google Scholar 

  5. Silva, V.O., L.O. Soares, A. Silva Junior, H.C. Mantovani, Y.F. Chang, and M.A. Moreira. 2014. Biofilm formation on biotic and abiotic surfaces in the presence of antimicrobials by escherichia coli isolates from cases of bovine mastitis. Applied and Environmental Microbiology 80: 6136–6145.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  6. Song X, Zhang W, Wang T, Jiang H, Zhang Z, Fu Y, et al. 2014. Geniposide plays an anti-inflammatory role via regulating TLR4 and downstream signaling pathways in lipopolysaccharide-induced mastitis in mice. Inflammation.

  7. Atabai, K., and M.A. Matthay. 2002. The pulmonary physician incritical care. 5: acute lung injury and the acute respiratory distress syndrome: denitions and epidemiology. Thorax 57: 452–458.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Rubenfeld, G.D., E. Caldwell, E. Peabody, J. Weaver, D.P. Martin, M. Neff, et al. 2005. Incidence and outcomes of acute lung injury. The New England Journal of Medicine 353: 1685–1693.

    Article  PubMed  CAS  Google Scholar 

  9. Oliver, S., and L. Calvinho. 1995. Influence of inflammation on mammary gland metabolism and milk composition. Journal of Animal Science 73: 18–33.

    Google Scholar 

  10. Fu, Y.H., B. Liu, X.S. Feng, Z.C. Liu, D.J. Liang, F.Y. Li, et al. 2013. Lipopolysaccharide increases toll-like receptor 4 and downstream toll-like receptor signaling molecules expression in bovine endometrial epithelial cells. Veterinary Immunology and Immunopathology 151: 20–27.

    Article  PubMed  CAS  Google Scholar 

  11. Li, F., D. Liang, Z. Yang, T. Wang, W. Wang, X. Song, et al. 2013. Astragalin suppresses inflammatory responses via down-regulation of NF-kappaB signaling pathway in lipopolysaccharide-induced mastitis in a murine model. International Immunopharmacology 17: 478–482.

    Article  PubMed  CAS  Google Scholar 

  12. Costa, J.C., F. Espeschit Ide, F.A. Pieri, A. Benjamin Ldos, and M.A. Moreira. 2012. Increased production of biofilms by Escherichia coli in the presence of enrofloxacin. Veterinary Microbiology 160: 488–490.

    Article  PubMed  CAS  Google Scholar 

  13. Odenholt, I. 2001. Pharmacodynamic effects of subinhibitory antibiotic concentrations. International Journal of Antimicrobial Agents 17: 1–8.

    Article  PubMed  CAS  Google Scholar 

  14. Uniyal, S.K., K.N. Singh, P. Jamwal, and B. Lal. 2006. Traditional use of medicinal plants among the tribal communities of Chhota Bhangal, Western Himalaya. Journal of Ethnobiology and Ethnomedicine 2: 14–21.

    Article  PubMed Central  PubMed  Google Scholar 

  15. Ahmed, E., M. Arshad, M. Ahmad, M. Saeed, and M. Ishaque. 2004. Ethnopharmacological survey of some medicinally important plants of Galliyat areas of NWFP, Pakistan. Asian Journal of Plant Sciences 3: 410–415.

    Article  Google Scholar 

  16. Heitor, A., L. Izandina, P. Gilmar, D. Piló-Veloso, and A. Antônio-Flávio. 2008. Antioxidant activity of (+)-bergenin-a phytoconstituent isolated from the bark of Sacoglottis uchi Huber (Humireaceae). Organic and Biomolecular Chemistry 6: 2713–2718.

    Article  CAS  Google Scholar 

  17. Swarnalakshmi, T., M.G. Sethuraman, N. Sulochana, and R. Arivudainambi. 1984. Antimicrobial activity of bergenin from Endopleura uchi. Current Science 53: 917.

    CAS  Google Scholar 

  18. Uddin, G., A. Sadat, and B.S. Siddiqui. 2014. Comparative antioxidant and antiplasmodial activities of 11-O-galloylbergenin and bergenin isolated from Bergenia ligulata. Tropical Biomedicine 31: 143–148.

    PubMed  CAS  Google Scholar 

  19. Takahashi, H., M. Kosaka, Y. Watanabe, K. Nakade, and Y. Fukuyama. 2003. Synthesis and neuroprotective activity of bergenin derivatives with antioxidant activity. Bioorganic & Medicinal Chemistry 11: 1781–1788.

    Article  CAS  Google Scholar 

  20. Nazir, N., S. Koul, M.A. Qurishi, S.C. Taneja, S.F. Ahmad, S. Bani, et al. 2007. Immunomodulatory effect of bergenin and norbergenin against adjuvant-induced arthritis—a flow cytometric study. Journal of Ethnopharmacology 112: 401–405.

    Article  PubMed  CAS  Google Scholar 

  21. Shah, M.R., M. Arfan, H. Amin, Z. Hussain, M.I. Qadir, M.I. Choudhary, et al. 2012. Synthesis of new bergenin derivatives as potent inhibitors of inflammatory mediators NO and TNF-alpha. Bioorganic & Medicinal Chemistry Letters 22: 2744–2747.

    Article  CAS  Google Scholar 

  22. Atakisi, O., H. Oral, E. Atakisi, O. Merhan, S. Metin Pancarci, A. Ozcan, et al. 2010. Subclinical mastitis causes alterations in nitric oxide, total oxidant and antioxidant capacity in cow milk. Research in Veterinary Science 89: 10–13.

    Article  PubMed  CAS  Google Scholar 

  23. Peirson S.N., Butler J.N., Foster R.G. 2003. Experimental validation of novel and conventional approaches to quantitative real-time PCR data analysis. Nucleic Acids Research 31.

  24. Pfaffl, M.W. 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research 29: e45.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Seegers, H., C. Fourichon, and F. Beaudeau. 2003. Production effects related to mastitis and mastitis economics in dairy cattle herds. Veterinary Research 34: 475–491.

    Article  PubMed  Google Scholar 

  26. Kim, K.W., J. Im, J.H. Jeon, H.G. Lee, C.H. Yun, and S.H. Han. 2011. Staphylococcus aureus induces IL-1 beta expression through the activation of MAP kinases and AP-1, CRE and NF-kappa B transcription factors in the bovine mammary gland epithelial cells. Comparative Immunology and Microbiology 34: 347–354.

    Article  Google Scholar 

  27. Nazir, N., S. Koul, M.A. Qurishi, M.H. Najar, and M.I. Zargar. 2011. Evaluation of antioxidant and antimicrobial activities of bergenin and its derivatives obtained by chemoenzymatic synthesis. European Journal of Medicinal Chemistry 46: 2415–2420.

    Article  PubMed  CAS  Google Scholar 

  28. Li, D., N. Zhang, Y. Cao, W. Zhang, G. Su, Y. Sun, et al. 2013. Emodin ameliorates lipopolysaccharide-induced mastitis in mice by inhibiting activation of NF-kappaB and MAPKs signal pathways. European Journal of Pharmacology 705: 79–85.

    Article  PubMed  CAS  Google Scholar 

  29. Boudjellab, N., H.S. Chan-Tang, and X. Zhao. 2000. Bovine interleukin-1 expression by cultured mammary epithelial cells (MAC-T) and its involvement in the release of MAC-T derived interleukin-8. Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology 127: 191–199.

    Article  CAS  Google Scholar 

  30. Li, B., J. Li, X. Pan, G. Ding, H. Cao, W. Jiang, J. Zheng, and H. Zhou. 2010. Artesunate protects sepsis model mice challenged with Staphylococcus aureus by decreasing TNF-alpha release via inhibition TLR2 and Nod2 mRNA expressions and transcription factor NF-kappaB activation. International Immunopharmacology 10: 344–350.

    Article  PubMed  CAS  Google Scholar 

  31. Lo Faro, M.L., B. Fox, J.L. Whatmore, P.G. Winyard, and M. Whiteman. 2014. Hydrogen sulfide and nitric oxide interactions in inflammation. Nitric Oxide: Biology and Chemistry/Official Journal of the Nitric Oxide Society 41C: 38–47.

    Article  CAS  Google Scholar 

  32. Fu, Y.H., B. Liu, J.H. Liu, Z.C. Liu, D.J. Liang, F.Y. Li, et al. 2012. Geniposide, from Gardenia jasminoides Ellis, inhibits the inflammatory response in the primary mouse macrophages and mouse models. International Immunopharmacology 14: 792–798.

    Article  PubMed  CAS  Google Scholar 

  33. Dilshara, M.G., K.T. Lee, R.G.P.T. Jayasooriya, C.H. Kang, S.R. Park, Y.H. Choi, et al. 2014. Downregulation of NO and PGE(2) in LPS-stimulated BV2 microglial cells by trans-isoferulic acid via suppression of PI3K/Akt-dependent NF-kappa B and activation of Nrf2-mediated HO-1. International Immunopharmacology 18: 203–211.

    Article  PubMed  CAS  Google Scholar 

  34. Guo, M., N. Zhang, D. Li, D. Liang, Z. Liu, F. Li, et al. 2013. Baicalin plays an anti-inflammatory role through reducing nuclear factor-kappaB and p38 phosphorylation in S. aureus-induced mastitis. International Immunopharmacology 16: 125–130.

    Article  PubMed  CAS  Google Scholar 

  35. Miller, L.S., E.M. Pietras, L.H. Uricchio, K. Hirano, S. Rao, H. Lin, R.M. O’Connell, Y. Iwakura, A.L. Cheung, G. Cheng, and R.L. Modlin. 2007. Inflammasome-mediated production of IL-1beta is required for neutrophil recruitment against Staphylococcus aureus in vivo. Journal of Immunology 179: 6933–6942.

    Article  CAS  Google Scholar 

  36. Boulanger, D., E. Brouillette, F. Jaspar, F. Malouin, J. Mainil, F. Bureau, and P. Lekeux. 2007. Helenalin reduces Staphylococcus aureus infection in vitro and in vivo. Veterinary Microbiology 119: 330–338.

    Article  PubMed  CAS  Google Scholar 

  37. Li, Q., and I.M. Verma. 2002. NF-kappaB regulation in the immune system. Nature Reviews Immunology 2: 725–734.

    Article  PubMed  CAS  Google Scholar 

  38. Godowski, P.J. 2005. A smooth operator for LPS responses. Nature Immunology 6: 544–546.

    Article  PubMed  CAS  Google Scholar 

  39. Liang, D.J., Y. Sun, Y.B. Shen, F.Y. Li, X.J. Song, E.S. Zhou, et al. 2013. Shikonin exerts anti-inflammatory effects in a murine model of lipopolysaccharide-induced acute lung injury by inhibiting the nuclear factor-kappaB signaling pathway. International Immunopharmacology 16: 475–480.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (Nos. 31272622, 31201925), the Research Fund for the Doctoral Program of Higher Education of China (Nos. 20110061130010, 20120061120098), and the Fundamental Research Funds for the Central Universities (No. 2662014BQ024)

Author information

Authors and Affiliations

  1. College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, People’s Republic of China

    Xue-jiao Gao, Ze-cai Zhang, Tian-cheng Wang & Yong-guo Cao

  2. College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, People’s Republic of China

    Meng-yao Guo

  3. Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, People’s Republic of China

    Nai-sheng Zhang

Authors
  1. Xue-jiao Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Meng-yao Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ze-cai Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tian-cheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yong-guo Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nai-sheng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nai-sheng Zhang.

Additional information

Xue-jiao Gao and Meng-yao Guo contributed equally to this article.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gao, Xj., Guo, My., Zhang, Zc. et al. Bergenin Plays an Anti-Inflammatory Role via the Modulation of MAPK and NF-κB Signaling Pathways in a Mouse Model of LPS-Induced Mastitis. Inflammation 38, 1142–1150 (2015). https://doi.org/10.1007/s10753-014-0079-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-014-0079-8

KEY WORDS

Search

Navigation