Abstract
Background and objective
Mastitis is defined as inflammation of the mammary gland in domestic dairy animals and humans. Salidroside, a major component isolated from Rhodiola rosea L., has potent anti-inflammatory properties, but whether it can be used in mastitis treatment has not yet been investigated. The aim of this study was to assess the protective effects of salidroside against lipopolysaccharide (LPS)-induced mastitis in mice and the mechanism of action.
Methods and results
We used a mouse mastitis model in which mammary gland inflammation was induced by LPS challenge. Salidroside administered 1 h before LPS infusion significantly attenuated inflammatory cell infiltration, reduced the activity of myeloperoxidase in mammary tissue, and decreased the concentration of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in a dose-dependent manner. Further studies revealed that salidroside down-regulated phosphorylation of LPS-induced nuclear transcription factor-kappaB (NF-κB) p65 and inhibitor of NF-κB α (IκBα) in the NF-κB signal pathway, and suppressed phosphorylation of p38, extracellular signal-regulated kinase (ERK) and c-jun NH2-terminal kinase (JNK) in MAPKs signal pathways.
Conclusions
This study demonstrates that salidroside is an effective suppressor of inflammation and may be a candidate for the prophylaxis of mastitis.
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References
Viguier C, et al. Mastitis detection: current trends and future perspectives. Trends Biotechnol. 2009;27(8):486–93.
Bradley AJ. Bovine mastitis: an evolving disease. Vet J. 2002;164(2):116–28.
Burvenich C, et al. Severity of E. coli mastitis is mainly determined by cow factors. Vet Res. 2003;34(5):521–64.
Elazar S, et al. Essential role of neutrophils but not mammary alveolar macrophages in a murine model of acute Escherichia coli mastitis. Vet Res. 2010;41(4):53.
Bannerman DD, et al. Increased levels of LPS-binding protein in bovine blood and milk following bacterial lipopolysaccharide challenge. J Dairy Sci. 2003;86(10):3128–37.
Lee JW, et al. Elevated milk soluble CD14 in bovine mammary glands challenged with Escherichia coli lipopolysaccharide. J Dairy Sci. 2003;86(7):2382–9.
Ma C, et al. Preparative purification of salidroside from Rhodiola rosea by two-step adsorption chromatography on resins. J Sep Sci. 2009;32(2):185–91.
Wu YL, et al. Protective effects of salidroside against acetaminophen-induced toxicity in mice. Biol Pharm Bull. 2008;31(8):1523–9.
Lang CH, et al. Endotoxin stimulates in vivo expression of inflammatory cytokines tumor necrosis factor alpha, interleukin-1 beta, -6, and high-mobility-group protein-1 in skeletal muscle. Shock. 2003;19(6):538–46.
Chu X, et al. Ceftiofur attenuates lipopolysaccharide-induced acute lung injury. Int Immunopharmacol. 2010;10(5):600–4.
Guan S, et al. Salidroside attenuates LPS-induced pro-inflammatory cytokine responses and improves survival in murine endotoxemia. Int Immunopharmacol. 2011;11(12):2194–9.
Brouillette E, Malouin F. The pathogenesis and control of Staphylococcus aureus-induced mastitis: study models in the mouse. Microbes Infect. 2005;7(3):560–8.
Zhu YM, et al. Protective effect of CpG-DNA against mastitis induced by Staphylococcus aureus infection in a rat model. Int Immunopharmacol. 2007;7(4):435–43.
Gonen E, et al. Toll-like receptor 4 is needed to restrict the invasion of Escherichia coli P4 into mammary gland epithelial cells in a murine model of acute mastitis. Cell Microbiol. 2007;9(12):2826–38.
Notebaert S, Meyer E. Mouse models to study the pathogenesis and control of bovine mastitis: a review. Vet Q. 2006;28(1):2–13.
Gupta V, et al. A dose dependent adaptogenic and safety evaluation of Rhodiola imbricata Edgew, a high altitude rhizome. Food Chem Toxicol. 2008;46(5):1645–52.
Krawisz JE, Sharon P, Stenson WF. Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity: assessment of inflammation in rat and hamster models. Gastroenterology. 1984;87(6):1344–50.
Klebanoff SJ. Myeloperoxidase: friend and foe. J Leukoc Biol. 2005;77(5):598–625.
Zheng J, Watson AD, Kerr DE. Genome-wide expression analysis of lipopolysaccharide-induced mastitis in a mouse model. Infect Immun. 2006;74(3):1907–15.
Paape M, et al. Defense of the bovine mammary gland by polymorphonuclear neutrophil leukocytes. J Mammary Gland Biol Neoplasia. 2002;7(2):109–21.
Yan S, et al. Anti-inflammatory effects of ivermectin in mouse model of allergic asthma. Inflamm Res. 2011;60(6):589–96.
Boudjellab N, Chan-Tang HS, Zhao X. Bovine interleukin-1 expression by cultured mammary epithelial cells (MAC-T) and its involvement in the release of MAC-T derived interleukin-8. Comp Biochem Physiol A Mol Integr Physiol. 2000;127(2):191–9.
Hirohashi N, Morrison DC. Low-dose lipopolysaccharide (LPS) pretreatment of mouse macrophages modulates LPS-dependent interleukin-6 production in vitro. Infect Immun. 1996;64(3):1011–5.
Hirohashi N, Lei MG, Morrison DC. LPS pretreatment of mouse peritoneal macrophages differentially modulates TNF alpha and iNOS expression. J Endotoxin Res. 1999;5(5–6):251–60.
Schmitz S, et al. Short-term changes of mRNA expression of various inflammatory factors and milk proteins in mammary tissue during LPS-induced mastitis. Domest Anim Endocrinol. 2004;26(2):111–26.
Tracey KJ, Cerami A. Tumor necrosis factor: a pleiotropic cytokine and therapeutic target. Annu Rev Med. 1994;45:491–503.
Blakemore AI, et al. Interleukin-1 receptor antagonist gene polymorphism as a disease severity factor in systemic lupus erythematosus. Arthritis Rheum. 1994;37(9):1380–5.
Panesar N, Tolman K, Mazuski JE. Endotoxin stimulates hepatocyte interleukin-6 production. J Surg Res. 1999;85(2):251–8.
Jirik FR, et al. Bacterial lipopolysaccharide and inflammatory mediators augment IL-6 secretion by human endothelial cells. J Immunol. 1989;142(1):144–7.
Sironi M, et al. IL-1 stimulates IL-6 production in endothelial cells. J Immunol. 1989;142(2):549–53.
Miao JF, et al. Evaluation of the changes of immune cells during lipopolysaccharide-induced mastitis in rats. Cytokine. 2007;40(2):135–43.
Li Q, Verma IM. NF-kappaB regulation in the immune system. Nat Rev Immunol. 2002;2(10):725–34.
Godowski PJ. A smooth operator for LPS responses. Nat Immunol. 2005;6(6):544–6.
Acknowledgments
This work was supported by a grant from the National Natural Science Foundation of China (No. 30972225, 30771596) and the Research Fund for the Doctoral Program of Higher Education of China (No. 20110061130010).
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Responsible Editor: Graham Wallace.
D. Li and Y. Fu contributed equally to this work.
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Li, D., Fu, Y., Zhang, W. et al. Salidroside attenuates inflammatory responses by suppressing nuclear factor-κB and mitogen activated protein kinases activation in lipopolysaccharide-induced mastitis in mice. Inflamm. Res. 62, 9–15 (2013). https://doi.org/10.1007/s00011-012-0545-4
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DOI: https://doi.org/10.1007/s00011-012-0545-4