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Licochalcone A Attenuates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting NF-κB Activation

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Abstract

Licochalcone A (Lico A), a flavonoid found in licorice root (Glycyrrhiza glabra), has been reported to have anti-inflammatory activity. However, the protective effects of Lico A on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) remains unclear. In this study, using a mouse model of LPS-induced AKI, we investigated the protective effects and mechanism of Lico A on LPS-induced AKI in mice. LPS-induced kidney injury was assessed by detecting kidney histological study, blood urea nitrogen (BUN), and creatinine levels. The production of inflammatory cytokines TNF-α, IL-6, and IL-1β in serum and kidney tissues was detected by ELISA. The activation of NF-κB was measured by western blot analysis. Our results showed that Lico A dose-dependently attenuated LPS-induced kidney histopathologic changes, serum BUN, and creatinine levels. Lico A also suppressed LPS-induced TNF-α, IL-6, and IL-1β production both in serum and kidney tissues. Furthermore, our results showed that Lico A significantly inhibited LPS-induced NF-κB activation. In conclusion, our results suggest that Lico A has protective effects against LPS-induced AKI and Lico A exhibits its anti-inflammatory effects through inhibiting LPS-induced NF-κB activation.

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References

  1. Marshall, J.C., J.-L. Vincent, G. Guyatt, D.C. Angus, E. Abraham, G. Bernard, C. Bombardier, T. Calandra, H.S. Jørgensen, and R. Sylvester. 2005. Outcome measures for clinical research in sepsis: a report of the 2nd Cambridge Colloquium of the International Sepsis forum. Critical Care Medicine 33: 1708–1716.

    Article  PubMed  Google Scholar 

  2. Cai, B., E.A. Deitch, and L. Ulloa. 2010. Novel insights for systemic inflammation in sepsis and hemorrhage. Mediators of Inflammation. doi:10.1155/2010/642462.

    PubMed  PubMed Central  Google Scholar 

  3. Zarjou, A., and A. Agarwal. 2011. Sepsis and acute kidney injury. Journal of the American Society of Nephrology 22: 999–1006.

    Article  PubMed  Google Scholar 

  4. Cunningham, P.N., Y. Wang, R. Guo, G. He, and R.J. Quigg. 2004. Role of Toll-like receptor 4 in endotoxin-induced acute renal failure. The Journal of Immunology 172: 2629–2635.

    Article  CAS  PubMed  Google Scholar 

  5. Gupta, A., G.J. Rhodes, D.T. Berg, B. Gerlitz, B.A. Molitoris, and B.W. Grinnell. 2007. Activated protein C ameliorates LPS-induced acute kidney injury and downregulates renal INOS and angiotensin 2. American Journal of Physiology—Renal Physiology 293: F245–F254.

    Article  CAS  PubMed  Google Scholar 

  6. Cho, S.-Y., S.-J. Park, M.-J. Kwon, T.-S. Jeong, S.-H. Bok, W.-Y. Choi, W.-I. Jeong, S.-Y. Ryu, S.-H. Do, and C.-S. Lee. 2003. Quercetin suppresses proinflammatory cytokines production through MAP kinases and NF-κB pathway in lipopolysaccharide-stimulated macrophage. Molecular and Cellular Biochemistry 243: 153–160.

    Article  CAS  PubMed  Google Scholar 

  7. Kinsey, G.R., L. Li, and M.D. Okusa. 2008. Inflammation in acute kidney injury. Nephron Experimental Nephrology 109: e102–e107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Liu, C.-M., Y.-Z. Sun, J.-M. Sun, J.-Q. Ma, and C. Cheng. 2012. Protective role of quercetin against lead-induced inflammatory response in rat kidney through the ROS-mediated MAPKs and NF-κB pathway. Biochimica et Biophysica Acta (BBA)—General Subjects 1820: 1693–1703.

    Article  CAS  Google Scholar 

  9. Shen, H., G. Zeng, G. Tang, X. Cai, L. Bi, C. Huang, and Y. Yang. 2014. Antimetastatic effects of licochalcone A on oral cancer via regulating metastasis-associated proteases. Tumour Biology 35: 7467–7474.

    Article  CAS  PubMed  Google Scholar 

  10. Fontes, L.B., Dias D. Dos Santos, L.S. de Carvalho, H.L. Mesquita, Reis L. da Silva, A.T. Dias, A.A. Da Silva Filho, and J.O. do Amaral Correa. 2014. Immunomodulatory effects of licochalcone A on experimental autoimmune encephalomyelitis. Journal of Pharmacy and Pharmacology 66: 886–894.

    CAS  PubMed  Google Scholar 

  11. Kwon, H.S., J.H. Park, D.H. Kim, Y.H. Kim, J.H. Park, H.K. Shin, and J.K. Kim. 2008. Licochalcone A isolated from licorice suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice. Journal of Molecular Medicine 86: 1287–1295.

    Article  CAS  PubMed  Google Scholar 

  12. Chu, X., X. Ci, M. Wei, X. Yang, Q. Cao, M. Guan, H. Li, Y. Deng, H. Feng, and X. Deng. 2012. Licochalcone a inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo. Journal of Agricultural and Food Chemistry 60: 3947–3954.

    Article  CAS  PubMed  Google Scholar 

  13. Simmons, E.M., J. Himmelfarb, M.T. Sezer, G.M. Chertow, R.L. Mehta, E.P. Paganini, S. Soroko, S. Freedman, K. Becker, and D. Spratt. 2004. Plasma cytokine levels predict mortality in patients with acute renal failure. Kidney International 65: 1357–1365.

    Article  CAS  PubMed  Google Scholar 

  14. Murray, P., and J. Hall. 2000. Renal replacement therapy for acute renal failure. American Journal of Respiratory and Critical Care Medicine 162: 777–781.

    Article  CAS  PubMed  Google Scholar 

  15. Bostom, A.G., F. Kronenberg, and E. Ritz. 2002. Predictive performance of renal function equations for patients with chronic kidney disease and normal serum creatinine levels. Journal of the American Society of Nephrology 13: 2140–2144.

    Article  CAS  PubMed  Google Scholar 

  16. Clarkson, P.M., A.K. Kearns, P. Rouzier, R. Rubin, and P.D. Thompson. 2006. Serum creatine kinase levels and renal function measures in exertional muscle damage. Medicine and Science in Sports and Exercise 38: 623.

    Article  CAS  PubMed  Google Scholar 

  17. House, A.A., and C. Ronco. 2008. Extracorporeal blood purification in sepsis and sepsis-related acute kidney injury. Blood Purification 26: 30–35.

    Article  PubMed  Google Scholar 

  18. Lee, D.H., M.H. Park, C.J. Hwang, J.Y. Hwang, H.S. Yoon, D.Y. Yoon, and J.T. Hong. 2015. CCR5 deficiency increased susceptibility to lipopolysaccharide-induced acute renal injury. Archives of Toxicology. doi:10.1007/s00204-015-1530-9.

    Google Scholar 

  19. Xu, C., A. Chang, B.K. Hack, M.T. Eadon, S.L. Alper, and P.N. Cunningham. 2014. TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis. Kidney International 85: 72–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Miyazaki, H., J. Morishita, M. Ueki, K. Nishina, S. Shiozawa, and N. Maekawa. 2012. The effects of a selective inhibitor of c-Fos/activator protein-1 on endotoxin-induced acute kidney injury in mice. BMC Nephrology 13.

  21. Xu, D., M. Chen, X. Ren, X. Ren, and Y. Wu. 2014. Leonurine ameliorates LPS-induced acute kidney injury via suppressing ROS-mediated NF-kappaB signaling pathway. Fitoterapia 97: 148–155.

    Article  CAS  PubMed  Google Scholar 

  22. Takahashi, K., H. Mizukami, K. Kamata, W. Inaba, N. Kato, C. Hibi, and S. Yagihashi. 2012. Amelioration of acute kidney injury in lipopolysaccharide-induced systemic inflammatory response syndrome by an aldose reductase inhibitor, fidarestat. Plos One 7.

  23. Vallabhapurapu, S., and M. Karin. 2009. Regulation and function of NF-κB transcription factors in the immune system. Annual Review of Immunology 27: 693–733.

    Article  CAS  PubMed  Google Scholar 

  24. Bonizzi, G., and M. Karin. 2004. The two NF-κB activation pathways and their role in innate and adaptive immunity. Trends in Immunology 25: 280–288.

    Article  CAS  PubMed  Google Scholar 

  25. Sanz, A.B., M.D. Sanchez-Niño, A.M. Ramos, J.A. Moreno, B. Santamaria, M. Ruiz-Ortega, J. Egido, and A. Ortiz. 2010. NF-κB in renal inflammation. Journal of the American Society of Nephrology 21: 1254–1262.

    Article  CAS  PubMed  Google Scholar 

  26. Baldwin Jr., A.S. 1996. The NF-κB and IκB proteins: new discoveries and insights. Annual Review of Immunology 14: 649–681.

    Article  CAS  PubMed  Google Scholar 

  27. Fitzgerald, K.A., D.C. Rowe, B.J. Barnes, D.R. Caffrey, A. Visintin, E. Latz, B. Monks, P.M. Pitha, and D.T. Golenbock. 2003. LPS-TLR4 signaling to IRF-3/7 and NF-κB involves the toll adapters TRAM and TRIF. The Journal of Experimental Medicine 198: 1043–1055.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Jun Liu.

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All animal experiments were performed in accordance with the Health’s Guide for the Care and Use of Laboratory Animals published by the US National Institute of Health.

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The authors declare that they have no competing interests.

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Hu, J., Liu, J. Licochalcone A Attenuates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting NF-κB Activation. Inflammation 39, 569–574 (2016). https://doi.org/10.1007/s10753-015-0281-3

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