Skip to main content
Top
Published in: Inflammation 3/2015

01-06-2015

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

Authors: Xue-jiao Gao, Meng-yao Guo, Ze-cai Zhang, Tian-cheng Wang, Yong-guo Cao, Nai-sheng Zhang

Published in: Inflammation | Issue 3/2015

Login to get access

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.
Literature
1.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
2.
go back to reference Melchior, M.B., H. Vaarkamp, and J. Fink-Gremmels. 2006. Biofilms: a role in recurrent mastitis infections? Veterinary Journal 171: 398–407.CrossRef Melchior, M.B., H. Vaarkamp, and J. Fink-Gremmels. 2006. Biofilms: a role in recurrent mastitis infections? Veterinary Journal 171: 398–407.CrossRef
3.
go back to reference 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.CrossRef 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.CrossRef
4.
go back to reference Bradley, A.J. 2002. Bovine mastitis: an evolving disease. Veterinary Journal 164: 116–128.CrossRef Bradley, A.J. 2002. Bovine mastitis: an evolving disease. Veterinary Journal 164: 116–128.CrossRef
5.
go back to reference 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.CrossRefPubMedCentralPubMed 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.CrossRefPubMedCentralPubMed
6.
go back to reference 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. 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.
go back to reference 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.CrossRefPubMedCentralPubMed 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.CrossRefPubMedCentralPubMed
8.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
9.
go back to reference Oliver, S., and L. Calvinho. 1995. Influence of inflammation on mammary gland metabolism and milk composition. Journal of Animal Science 73: 18–33. Oliver, S., and L. Calvinho. 1995. Influence of inflammation on mammary gland metabolism and milk composition. Journal of Animal Science 73: 18–33.
10.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
11.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
12.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
13.
go back to reference Odenholt, I. 2001. Pharmacodynamic effects of subinhibitory antibiotic concentrations. International Journal of Antimicrobial Agents 17: 1–8.CrossRefPubMed Odenholt, I. 2001. Pharmacodynamic effects of subinhibitory antibiotic concentrations. International Journal of Antimicrobial Agents 17: 1–8.CrossRefPubMed
14.
go back to reference 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.CrossRefPubMedCentralPubMed 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.CrossRefPubMedCentralPubMed
15.
go back to reference 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.CrossRef 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.CrossRef
16.
go back to reference 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.CrossRef 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.CrossRef
17.
go back to reference Swarnalakshmi, T., M.G. Sethuraman, N. Sulochana, and R. Arivudainambi. 1984. Antimicrobial activity of bergenin from Endopleura uchi. Current Science 53: 917. Swarnalakshmi, T., M.G. Sethuraman, N. Sulochana, and R. Arivudainambi. 1984. Antimicrobial activity of bergenin from Endopleura uchi. Current Science 53: 917.
18.
go back to reference 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 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
19.
go back to reference 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.CrossRef 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.CrossRef
20.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
21.
go back to reference 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.CrossRef 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.CrossRef
22.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
23.
go back to reference 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. 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.
25.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
26.
go back to reference 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.CrossRef 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.CrossRef
27.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
28.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
29.
go back to reference 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.CrossRef 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.CrossRef
30.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
31.
go back to reference 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.CrossRef 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.CrossRef
32.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
33.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
34.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
35.
go back to reference 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.CrossRef 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.CrossRef
36.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
37.
go back to reference Li, Q., and I.M. Verma. 2002. NF-kappaB regulation in the immune system. Nature Reviews Immunology 2: 725–734.CrossRefPubMed Li, Q., and I.M. Verma. 2002. NF-kappaB regulation in the immune system. Nature Reviews Immunology 2: 725–734.CrossRefPubMed
38.
39.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
Metadata
Title
Bergenin Plays an Anti-Inflammatory Role via the Modulation of MAPK and NF-κB Signaling Pathways in a Mouse Model of LPS-Induced Mastitis
Authors
Xue-jiao Gao
Meng-yao Guo
Ze-cai Zhang
Tian-cheng Wang
Yong-guo Cao
Nai-sheng Zhang
Publication date
01-06-2015
Publisher
Springer US
Published in
Inflammation / Issue 3/2015
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-014-0079-8

Other articles of this Issue 3/2015

Inflammation 3/2015 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.