Skip to main content
Top
Published in: Inflammation 6/2014

01-12-2014

Protective Effects of Chelerythrine Against Lipopolysaccharide-Induced Endotoxic Shock in Mice

Authors: Xiaofeng Niu, Qingli Mu, Weifeng Li, Huimin Huang, Huan Yao, Huani Li

Published in: Inflammation | Issue 6/2014

Login to get access

Abstract

Chelerythrine (CHE), a quaternary benzo[c]phenanthridine alkaloid, exhibits a wide spectrum of pharmacological effects. Although CHE has been used to treat various diseases, the protective effects of CHE on lipopolysaccharide (LPS)-induced endotoxic shock have not been explored. The aims of the study were to investigate the protective effects of CHE on LPS-induced endotoxic shock in mice and clarify the mechanism of the effects. We found that pretreatment with CHE (1, 5, and 10 mg/kg, po) at 1 and 12 h before injected intraperitoneally with 1 mg/kg LPS markedly decreased the production of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and myeloperoxidase (MPO) and attenuated the lung histopathological changes. Meanwhile, the effects were dependent on the inhibition of the expression of p65 nuclear factor κB (NF-κB). The protective effects of CHE on LPS-induced endotoxic shock can be attributed to attenuating inflammatory cytokines and inhibition of the expression of NF-κB.
Literature
1.
go back to reference Aoki, K., T. Tajima, Y. Yabushita, A. Nakamura, U. Nezu, M. Takahashi, M. Kimura, and Y. Terauchi. 2008. A novel initial codon mutation of the thiazide-sensitive Na-Cl cotransporter gene in a Japanese patient with Gitelman’s syndrome. Endocrine Journal 55: 557.PubMedCrossRef Aoki, K., T. Tajima, Y. Yabushita, A. Nakamura, U. Nezu, M. Takahashi, M. Kimura, and Y. Terauchi. 2008. A novel initial codon mutation of the thiazide-sensitive Na-Cl cotransporter gene in a Japanese patient with Gitelman’s syndrome. Endocrine Journal 55: 557.PubMedCrossRef
2.
go back to reference Freudenberg, M., and C. Galanos. 1990. Bacterial lipopolysaccharides: structure, metabolism and mechanisms of action. International Reviews of Immunology 6: 207–221.PubMedCrossRef Freudenberg, M., and C. Galanos. 1990. Bacterial lipopolysaccharides: structure, metabolism and mechanisms of action. International Reviews of Immunology 6: 207–221.PubMedCrossRef
3.
go back to reference Bone, R.C., C.J. Grodzin, and R.A. Balk. 1997. Sepsis: a new hypothesis for pathogenesis of the disease process. CHEST Journal 112: 235–243.CrossRef Bone, R.C., C.J. Grodzin, and R.A. Balk. 1997. Sepsis: a new hypothesis for pathogenesis of the disease process. CHEST Journal 112: 235–243.CrossRef
4.
go back to reference He, M., H.Y. Lau, S.W. Ng, and M. Bhatia. 2007. Chemokines in acute inflammation: regulation, function and therapeutic strategies. International Journal of Integrative Biology 1: 18. He, M., H.Y. Lau, S.W. Ng, and M. Bhatia. 2007. Chemokines in acute inflammation: regulation, function and therapeutic strategies. International Journal of Integrative Biology 1: 18.
5.
go back to reference Lappin, E., and A.J. Ferguson. 2009. Gram-positive toxic shock syndromes. The Lancet Infectious Diseases 9: 281–290.PubMedCrossRef Lappin, E., and A.J. Ferguson. 2009. Gram-positive toxic shock syndromes. The Lancet Infectious Diseases 9: 281–290.PubMedCrossRef
6.
go back to reference Jansen, M.J., T. Hendriks, M.T. Vogels, J.W. van der Meer, and R.J.A. Goris. 1996. Inflammatory cytokines in an experimental model for the multiple organ dysfunction syndrome. Critical Care Medicine 24: 1196–1202.PubMedCrossRef Jansen, M.J., T. Hendriks, M.T. Vogels, J.W. van der Meer, and R.J.A. Goris. 1996. Inflammatory cytokines in an experimental model for the multiple organ dysfunction syndrome. Critical Care Medicine 24: 1196–1202.PubMedCrossRef
7.
go back to reference Neurath, M.F., I. Fuss, M. Pasparakis, L. Alexopoulou, S. Haralambous, K.H. Meyer zum Büschenfelde, W. Strober, and G. Kollias. 1997. Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice. European Journal of Immunology 27: 1743–1750.PubMedCrossRef Neurath, M.F., I. Fuss, M. Pasparakis, L. Alexopoulou, S. Haralambous, K.H. Meyer zum Büschenfelde, W. Strober, and G. Kollias. 1997. Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice. European Journal of Immunology 27: 1743–1750.PubMedCrossRef
8.
go back to reference Blenman, K.R.M., F.R. Bahjat, L.L. Moldawer, and L. Morel. 2004. Aberrant signaling in the TNFα/TNF receptor 1 pathway of the NZM2410 lupus-prone mouse. Clinical Immunology 110: 124–133.PubMedCrossRef Blenman, K.R.M., F.R. Bahjat, L.L. Moldawer, and L. Morel. 2004. Aberrant signaling in the TNFα/TNF receptor 1 pathway of the NZM2410 lupus-prone mouse. Clinical Immunology 110: 124–133.PubMedCrossRef
9.
go back to reference Ma, X. 2001. TNF-α and IL-12: a balancing act in macrophage functioning. Microbes and Infection 3: 121–129.PubMedCrossRef Ma, X. 2001. TNF-α and IL-12: a balancing act in macrophage functioning. Microbes and Infection 3: 121–129.PubMedCrossRef
10.
go back to reference Yoshimoto, T., K. Nakanishi, S. Hirose, K. Hiroishi, H. Okamura, Y. Takemoto, A. Kanamaru, T. Hada, T. Tamura, and E. Kakishita. 1992. High serum IL-6 level reflects susceptible status of the host to endotoxin and IL-1/tumor necrosis factor. The Journal of Immunology 148: 3596–3603.PubMed Yoshimoto, T., K. Nakanishi, S. Hirose, K. Hiroishi, H. Okamura, Y. Takemoto, A. Kanamaru, T. Hada, T. Tamura, and E. Kakishita. 1992. High serum IL-6 level reflects susceptible status of the host to endotoxin and IL-1/tumor necrosis factor. The Journal of Immunology 148: 3596–3603.PubMed
11.
go back to reference Damas, P., D. Ledoux, M. Nys, Y. Vrindts, D. De Groote, P. Franchimont, and M. Lamy. 1992. Cytokine serum level during severe sepsis in human IL-6 as a marker of severity. Annals of Surgery 215: 356.PubMedCentralPubMedCrossRef Damas, P., D. Ledoux, M. Nys, Y. Vrindts, D. De Groote, P. Franchimont, and M. Lamy. 1992. Cytokine serum level during severe sepsis in human IL-6 as a marker of severity. Annals of Surgery 215: 356.PubMedCentralPubMedCrossRef
12.
go back to reference Bhatia, M., and S. Moochhala. 2004. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. The Journal of Pathology 202: 145–156.PubMedCrossRef Bhatia, M., and S. Moochhala. 2004. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. The Journal of Pathology 202: 145–156.PubMedCrossRef
13.
go back to reference LaRosa, S.P., and S.M. Opal. 2008. Sepsis strategies in development. Clinics in Chest Medicine 29: 735–747.PubMedCrossRef LaRosa, S.P., and S.M. Opal. 2008. Sepsis strategies in development. Clinics in Chest Medicine 29: 735–747.PubMedCrossRef
14.
go back to reference Klosterhalfen, B., K. Hörstmann-Jungemann, P. Vogel, S. Flohé, F. Offner, C.J. Kirkpatrick, and P.C. Heinrich. 1992. Time course of various inflammatory mediators during recurrent endotoxemia. Biochemical Pharmacology 43: 2103–2109.PubMedCrossRef Klosterhalfen, B., K. Hörstmann-Jungemann, P. Vogel, S. Flohé, F. Offner, C.J. Kirkpatrick, and P.C. Heinrich. 1992. Time course of various inflammatory mediators during recurrent endotoxemia. Biochemical Pharmacology 43: 2103–2109.PubMedCrossRef
15.
go back to reference Martich, G.D., A.J. Boujoukos, and A.F. Suffredini. 1993. Response of man to endotoxin. Immunobiology 187: 403–416.PubMedCrossRef Martich, G.D., A.J. Boujoukos, and A.F. Suffredini. 1993. Response of man to endotoxin. Immunobiology 187: 403–416.PubMedCrossRef
16.
go back to reference Szarka, R.J., N. Wang, L. Gordon, P.N. Nation, and R.H. Smith. 1997. A murine model of pulmonary damage induced by lipopolysaccharide via intranasal instillation. Journal of Immunological Methods 202: 49–57.PubMedCrossRef Szarka, R.J., N. Wang, L. Gordon, P.N. Nation, and R.H. Smith. 1997. A murine model of pulmonary damage induced by lipopolysaccharide via intranasal instillation. Journal of Immunological Methods 202: 49–57.PubMedCrossRef
17.
go back to reference Tracey, K.J., B. Beutler, S.F. Lowry, J. Merryweather, S. Wolpe, I.W. Milsark, R.J. Hariri, T.J. Fahey, A. Zentella, and J.D. Albert. 1986. Shock and tissue injury induced by recombinant human cachectin. Science 234: 470–474.PubMedCrossRef Tracey, K.J., B. Beutler, S.F. Lowry, J. Merryweather, S. Wolpe, I.W. Milsark, R.J. Hariri, T.J. Fahey, A. Zentella, and J.D. Albert. 1986. Shock and tissue injury induced by recombinant human cachectin. Science 234: 470–474.PubMedCrossRef
18.
go back to reference Kruidenier, La., and H. Verspaget. 2002. Oxidative stress as a pathogenic factor in inflammatory bowel disease—radicals or ridiculous? Alimentary Pharmacology & Therapeutics 16: 1997–2015.CrossRef Kruidenier, La., and H. Verspaget. 2002. Oxidative stress as a pathogenic factor in inflammatory bowel disease—radicals or ridiculous? Alimentary Pharmacology & Therapeutics 16: 1997–2015.CrossRef
19.
go back to reference Takeuchi, K., T. Yasuhiro, Y. Asada, and Y. Sugawa. 1998. Role of nitric oxide in pathogenesis of aspirin-induced gastric mucosal damage in rats. Digestion 59: 298–307.PubMedCrossRef Takeuchi, K., T. Yasuhiro, Y. Asada, and Y. Sugawa. 1998. Role of nitric oxide in pathogenesis of aspirin-induced gastric mucosal damage in rats. Digestion 59: 298–307.PubMedCrossRef
20.
21.
go back to reference Kim, I.-S., Y.-J. Park, S.-J. Yoon, and H.-B. Lee. 2010. Ephedrannin A and B from roots of Ephedra sinica inhibit lipopolysaccharide-induced inflammatory mediators by suppressing nuclear factor-κB activation in RAW 264.7 macrophages. International Immunopharmacology 10: 1616–1625.PubMedCrossRef Kim, I.-S., Y.-J. Park, S.-J. Yoon, and H.-B. Lee. 2010. Ephedrannin A and B from roots of Ephedra sinica inhibit lipopolysaccharide-induced inflammatory mediators by suppressing nuclear factor-κB activation in RAW 264.7 macrophages. International Immunopharmacology 10: 1616–1625.PubMedCrossRef
22.
go back to reference Wise, G.E., and S. Yao. 2003. Expression of tumour necrosis factor-alpha in the rat dental follicle. Archives of Oral Biology 48: 47–54.PubMedCrossRef Wise, G.E., and S. Yao. 2003. Expression of tumour necrosis factor-alpha in the rat dental follicle. Archives of Oral Biology 48: 47–54.PubMedCrossRef
23.
go back to reference Heinzel, F.P., R.M. Rerko, P. Ling, J. Hakimi, and D.S. Schoenhaut. 1994. Interleukin 12 is produced in vivo during endotoxemia and stimulates synthesis of gamma interferon. Infection and Immunity 62: 4244–4249.PubMedCentralPubMed Heinzel, F.P., R.M. Rerko, P. Ling, J. Hakimi, and D.S. Schoenhaut. 1994. Interleukin 12 is produced in vivo during endotoxemia and stimulates synthesis of gamma interferon. Infection and Immunity 62: 4244–4249.PubMedCentralPubMed
24.
go back to reference Suzuki, K., K. Tateda, T. Matsumoto, F. Gondaira, S. Tsujimoto, and K. Yamaguchi. 2000. Effects of interaction between Escherichia coli verotoxin and lipopolysaccharide on cytokine induction and lethality in mice. Journal of Medical Microbiology 49: 905–910.PubMed Suzuki, K., K. Tateda, T. Matsumoto, F. Gondaira, S. Tsujimoto, and K. Yamaguchi. 2000. Effects of interaction between Escherichia coli verotoxin and lipopolysaccharide on cytokine induction and lethality in mice. Journal of Medical Microbiology 49: 905–910.PubMed
25.
go back to reference Yadav, S.K., B. Adhikary, S. Chand, B. Maity, S.K. Bandyopadhyay, and S. Chattopadhyay. 2012. Molecular mechanism of indomethacin-induced gastropathy. Free Radical Biology and Medicine 52: 1175–1187.PubMedCrossRef Yadav, S.K., B. Adhikary, S. Chand, B. Maity, S.K. Bandyopadhyay, and S. Chattopadhyay. 2012. Molecular mechanism of indomethacin-induced gastropathy. Free Radical Biology and Medicine 52: 1175–1187.PubMedCrossRef
26.
go back to reference Remick, D.G., G.R. Bolgos, J. Siddiqui, J. Shin, and J.A. Nemzek. 2002. Six at six: interleukin-6 measured 6 h after the initiation of sepsis predicts mortality over 3 days. Shock 17: 463–467.PubMedCrossRef Remick, D.G., G.R. Bolgos, J. Siddiqui, J. Shin, and J.A. Nemzek. 2002. Six at six: interleukin-6 measured 6 h after the initiation of sepsis predicts mortality over 3 days. Shock 17: 463–467.PubMedCrossRef
27.
go back to reference Ito, H., M. Takazoe, Y. Fukuda, T. Hibi, K. Kusugami, A. Andoh, T. Matsumoto, T. Yamamura, J. Azuma, and N. Nishimoto. 2004. A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn’s disease. Gastroenterology 126: 989–996.PubMedCrossRef Ito, H., M. Takazoe, Y. Fukuda, T. Hibi, K. Kusugami, A. Andoh, T. Matsumoto, T. Yamamura, J. Azuma, and N. Nishimoto. 2004. A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn’s disease. Gastroenterology 126: 989–996.PubMedCrossRef
28.
go back to reference Luo, J., J. Cao, X. Jiang, and H. Cui. 2010. Effect of low molecular weight heparin rectal suppository on experimental ulcerative colitis in mice. Biomedicine & Pharmacotherapy 64: 441–445.CrossRef Luo, J., J. Cao, X. Jiang, and H. Cui. 2010. Effect of low molecular weight heparin rectal suppository on experimental ulcerative colitis in mice. Biomedicine & Pharmacotherapy 64: 441–445.CrossRef
29.
go back to reference Reinisch, W., C. Gasché, W. Tillinger, J. Wyatt, C. Lichtenberger, M. Willheim, C. Dejaco, T. Waldhör, S. Bakos, and H. Vogelsang. 1999. Clinical relevance of serum interleukin-6 in Crohn’s disease: single point measurements, therapy monitoring, and prediction of clinical relapse. The American Journal of Gastroenterology 94: 2156–2164.PubMedCrossRef Reinisch, W., C. Gasché, W. Tillinger, J. Wyatt, C. Lichtenberger, M. Willheim, C. Dejaco, T. Waldhör, S. Bakos, and H. Vogelsang. 1999. Clinical relevance of serum interleukin-6 in Crohn’s disease: single point measurements, therapy monitoring, and prediction of clinical relapse. The American Journal of Gastroenterology 94: 2156–2164.PubMedCrossRef
30.
go back to reference Buraczynska, M., L. Jozwiak, P. Ksiazek, E. Borowicz, and P. Mierzicki. 2007. Interleukin-6 gene polymorphism and faster progression to end-stage renal failure in chronic glomerulonephritis. Translational Research 150: 101–105.PubMedCrossRef Buraczynska, M., L. Jozwiak, P. Ksiazek, E. Borowicz, and P. Mierzicki. 2007. Interleukin-6 gene polymorphism and faster progression to end-stage renal failure in chronic glomerulonephritis. Translational Research 150: 101–105.PubMedCrossRef
31.
go back to reference Benamar, K., E.B. Geller, and M.W. Adler. 2002. Effect of a μ-opioid receptor-selective antagonist on interleukin-6 fever. Life Sciences 70(18): 2139–2145.PubMedCrossRef Benamar, K., E.B. Geller, and M.W. Adler. 2002. Effect of a μ-opioid receptor-selective antagonist on interleukin-6 fever. Life Sciences 70(18): 2139–2145.PubMedCrossRef
32.
go back to reference Beffa, D.C., A.J. Fischman, S.P. Fagan, V.F. Hamrahi, K.W. Paul, M. Kaneki, Y.-M. Yu, R.G. Tompkins, and E.A. Carter. 2011. Simvastatin treatment improves survival in a murine model of burn sepsis: role of interleukin 6. Burns 37: 222–226.PubMedCentralPubMedCrossRef Beffa, D.C., A.J. Fischman, S.P. Fagan, V.F. Hamrahi, K.W. Paul, M. Kaneki, Y.-M. Yu, R.G. Tompkins, and E.A. Carter. 2011. Simvastatin treatment improves survival in a murine model of burn sepsis: role of interleukin 6. Burns 37: 222–226.PubMedCentralPubMedCrossRef
33.
go back to reference Cheng, L.N., X.L. Huang, W. Shi, J.Y. Xiang, and H.T. Gan. 2009. Tetrandrine ameliorates dextran-sulfate-sodium-induced colitis in mice through inhibition of nuclear factor-κB activation. International Journal of Colorectal Disease 24: 5–12.PubMedCrossRef Cheng, L.N., X.L. Huang, W. Shi, J.Y. Xiang, and H.T. Gan. 2009. Tetrandrine ameliorates dextran-sulfate-sodium-induced colitis in mice through inhibition of nuclear factor-κB activation. International Journal of Colorectal Disease 24: 5–12.PubMedCrossRef
Metadata
Title
Protective Effects of Chelerythrine Against Lipopolysaccharide-Induced Endotoxic Shock in Mice
Authors
Xiaofeng Niu
Qingli Mu
Weifeng Li
Huimin Huang
Huan Yao
Huani Li
Publication date
01-12-2014
Publisher
Springer US
Published in
Inflammation / Issue 6/2014
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-014-9929-7

Other articles of this Issue 6/2014

Inflammation 6/2014 Go to the issue