, Volume 40, Issue 1, pp 275–284 | Cite as

Polysaccharides from Arnebia euchroma Ameliorated Endotoxic Fever and Acute Lung Injury in Rats Through Inhibiting Complement System



Arnebiaeuchroma (Royle) Johnst (Ruanzicao) is a traditional Chinese herbal medicine (TCM). It is extensively used in China and other countries for treatment of inflammatory diseases. It is known that hyper-activated complement system involves in the fever and acute lung injury (ALI) in rats. In our preliminary studies, anti-complementary activity of crude Arnebiaeuchroma polysaccharides (CAEP) had been demonstrated in vitro. This study aimed to investigate the role and mechanism of crude Arnebiaeuchroma polysaccharides (CAEP) using two animal models, which relate with inappropriate activation of complement system. In lipopolysaccharide (LPS)-induced fever model, the body temperature and leukocytes of peripheral blood in rats were significantly increased, while the complement levels of serum were remarkably decreased. CAEP administration alleviated the LPS-induced fever, reduced the number of leukocytes, and improved the levels of complement. Histological assay showed that there were severe damages and complement depositions in lung of the ALI rats. Further detection displayed that the oxidant stress was enhanced, and total hemolytic activity and C3/C4 levels in serum were decreased significantly in the ALI model group. Remarkably, CAEP not only attenuated the morphological injury, edema, and permeability in the lung but also significantly weakened the oxidant stress in bronchoalveolar lavage fluid (BALF) in the ALI rats. The levels of complement and complement depositions were improved by the CAEP treatment. In conclusion, the CAEP treatment ameliorated febrile response induced by LPS and acute lung injury induced by LPS plus ischemia-reperfusion. CAEP exerted beneficial effects on inflammatory disease potentially via inhibiting the inappropriate activation of complement system.


acute lung injury fever polysaccharides Arnebia euchroma complement 



This work was supported by grants from the Ministry of Science and Technology of China (2012ZX09301001-003), the National Natural Science Foundation of China (81330089, 30925042), the Committee of Science and Technology of Shanghai Municipality, China (10XD1405900, 08DZ1971202), and the Foundation for the Doctoral Program from the Ministry of Education of China (200802460055).

Compliance with Ethical Standards

The use of animals was approved by the Animal Ethical Committee of School of Pharmacy of Fudan University (Ethical Review No. 2011-9).

Conflict of Interest

The authors declare that they have no conflict of interest.

Supplementary material

10753_2016_478_MOESM1_ESM.pdf (318 kb)
ESM 1 (PDF 317 kb)


  1. 1.
    Carroll, M.V., and R.B. Sim. 2011. Complement in health and disease. Advanced Drug Delivery Reviews 63: 965–975.Google Scholar
  2. 2.
    Blatteis, C.M., S.X. Li, Z.H. Li, V. Perlik, and C. Feleder. 2004. Signaling the brain in systemic inflammation: The role of complement. Frontiers in Bioscience-Landmark 9: 915–931.Google Scholar
  3. 3.
    Li, S., S.A. Boackle, V.M. Holers, J.D. Lambris, and C.M. Blatteis. 2005. Complement component C5a is integral to the febrile response of mice to lipopolysaccharide. Neuroimmunomodulation 12: 67–80.Google Scholar
  4. 4.
    Flierl, M.A., Rittirsch, D., Sarma, J.V., Huber-Lang, M., and Ward, P.A. (2008). Adrenergic Regulation of complement-induced acute lung injury. In Current Topics in Complement Ii, Volume 632, J.D. Lambris, ed., pp. 93–103.Google Scholar
  5. 5.
    Li, W., J.-Y. Xie, H. Li, Y.-Y. Zhang, J. Cao, Z.-H. Cheng, and D.-F. Chen. 2012. Viola yedoensis liposoluble fraction ameliorates lipopolysaccharide-induced acute lung injury in mice. American Journal of Chinese Medicine 40: 1007–1018.Google Scholar
  6. 6.
    Derek Gilroy and Roel De Maeyer. 2015. New insights into the resolution of inflammation. Seminars in Immunology 27 (3):161–168.Google Scholar
  7. 7.
    Noris, M., and G. Remuzzi. 2013. Overview of complement activation and regulation. Seminars in Nephrology 33: 479–492.Google Scholar
  8. 8.
    Blatteis, C.M. 2003. Fever: Pathological or physiological, injurious or beneficial? Journal of Thermal Biology 28: 1–13.Google Scholar
  9. 9.
    Blatteis, C.M., S. Li, Z. Li, V. Perlik, and C. Feleder. 2004. Complement is required for the induction of endotoxic fever in guinea pigs and mice. Journal of Thermal Biology 29: 369–381.Google Scholar
  10. 10.
    Reiss, L.K., U. Uhlig, and S. Uhlig. 2012. Models and mechanisms of acute lung injury caused by direct insults. European Journal of Cell Biology 91: 590–601.Google Scholar
  11. 11.
    Sun, S., H. Wang, G. Zhao, Y. An, Y. Guo, L. Du, H. Song, F. Qiao, H. Yu, X. Wu, et al. 2011. Complement inhibition alleviates paraquat-induced acute lung injury. American Journal of Respiratory Cell and Molecular Biology 45: 834–842.Google Scholar
  12. 12.
    Dokladny, K., A. Kozak, M. Wachulec, E.S. Wallen, M.G. Menache, W. Kozak, M.J. Kluger, and P.L. Moseley. 2001. Effect of heat stress on LPS-induced febrile response in D-galactosamine-sensitized rats. American Journal of Physiology—Regulatory, Integrative and Comparative Physiology 280: R338–R344.Google Scholar
  13. 13.
    Brigham, K.L., and B. Meyrick. 1986. Endotoxin and lung injury. The American Review of Respiratory Disease 133: 913–927.Google Scholar
  14. 14.
    Seydel, U., Ulmer, A.J., Uhlig, S., and Rietschel, E.T. (2000). Lipopolysaccharide—A membrane-forming and inflammation-inducing bacterial macromolecule. Membrane Structure in Disease and Drug Therapy, 217–252.Google Scholar
  15. 15.
    Arumugam, T.V., T. Magnus, T.M. Woodruff, L.M. Proctor, I.A. Shiels, and S.M. Taylor. 2006. Complement mediators in ischemia-reperfusion injury. Clinica Chimica Acta; International Journal of Clinical Chemistry 374: 33–45.Google Scholar
  16. 16.
    Theodore J. Standiford and Peter A. Ward. 2015. Therapeutic targeting of acute lung injury and acute respiratory distress syndrome. Translational Research: The Journal of Laboratory and Clinical Medicine 167 (1): 183–191.Google Scholar
  17. 17.
    Fan, H., M. Yang, X. Che, Z. Zhang, H. Xu, K. Liu, and Q. Meng. 2012. Activity study of a hydroxynaphthoquinone fraction from Arnebia euchroma in experimental arthritis. Fitoterapia 83: 1226–1237.Google Scholar
  18. 18.
    Xiong, W., G. Luo, L. Zhou, Y. Zeng, and W. Yang. 2009. In vitro and in vivo antitumor effects of acetylshikonin isolated from Arnebia euchroma (Royle) Johnst (Ruanzicao) cell suspension cultures. Chinese Medicine 4: 14.Google Scholar
  19. 19.
    Kaith, N.S. Chauhan. 1996. Anti-inflammatory effect of Arnebia euchroma root extracts in rats. Journal of Ethnopharmacology 55: 77–80.Google Scholar
  20. 20.
    Singh, B., P.M. Sahu, S.C. Jain, and S. Singh. 2004. Estimation of naphthaquinones from Arnebia hispidissima (Lehm.) DC. in vivo and in vitro. I. Anti-inflammatory screening. Phytotherapy Research 18: 154–159.Google Scholar
  21. 21.
    Singh, B., M.K. Sharma, P.R. Meghwal, P.M. Sahu, and S. Singh. 2003. Anti-inflammatory activity of shikonin derivatives from Arnebia hispidissima. Phytomedicine 10: 375–380.Google Scholar
  22. 22.
    Mayer, M.M. 1961. On destruction of erythrocytes and other cells by antibody and complement. Cancer Research 21: 1262.Google Scholar
  23. 23.
    Cheng, X.Q., L.J. Song, H. Li, H. Di, Y.Y. Zhang, and D.F. Chen. 2012. Beneficial effect of the polysaccharides from Bupleurum smithii var. parvifolium on “two-hit” acute lung injury in rats. Inflammation 35: 1715–1722.Google Scholar
  24. 24.
    Wang, Z., H. Li, H. Xu, X.-L. Yue, X.-Q. Cheng, W.-J. Hou, Y.-Y. Zhang, and D.-F. Chen. 2009. Beneficial effect of Bupleurum polysaccharides on autoimmune disease induced by Campylobacter jejuni in BALB/c mice. Journal of Ethnopharmacology 124: 481–487.Google Scholar
  25. 25.
    Lu, W.-H., Q. Pan, F. Wang, Y.-F. Chen, and N.-B. Dai. 2012. Influence of culture conditions on arnebia euchroma hairy roots growth and shikonin content. Xibei Zhiwu Xuebao 32: 1686–1691.Google Scholar
  26. 26.
    Zhang, P., F. Wang, and C. Zhu. 2013. Influence of fungal elicitor and macroporous resin on shikonin accumulation in hairy roots of Arnebia euchroma (Royle) Johnst. Chinese Journal of Biotechnology 29: 214–223.Google Scholar
  27. 27.
    Moltz, H. 1993. Fever-causes and consequences. Neuroscience and Biobehavioral Reviews 17: 237–269.Google Scholar
  28. 28.
    Perlik, V., Z.G. Li, S. Goorha, L.R. Ballou, and C.M. Blatteis. 2005. LPS-activated complement, not LPS per se, triggers the early release of PGE2 by Kupffer cells. American Journal of Physiology—Regulatory, Integrative and Comparative Physiology 289: R332–R339.Google Scholar
  29. 29.
    Lang, J.D., and J.M. Hickman-Davis. 2005. One-hit, two-hit…is there really any benefit? Clinical and Experimental Immunology 141: 211–214.Google Scholar
  30. 30.
    Matthijsen, R.A., D. Huugen, N.T. Hoebers, B. De Vries, C.J. Peutz-Kootstra, Y. Aratani, M.R. Daha, J.W.C. Tervaert, W.A. Buurman, and P. Heeringa. 2007. Myeloperoxidase is critically involved in the induction of organ damage after renal ischemia reperfusion. American Journal of Pathology 171: 1743–1752.Google Scholar
  31. 31.
    Mao, Y.-F., X.-F. Zheng, J.-M. Cai, X.-M. You, X.-M. Deng, J.H. Zhang, L. Jiang, and X.-J. Sun. 2009. Hydrogen-rich saline reduces lung injury induced by intestinal ischemia/reperfusion in rats. Biochemical and Biophysical Research Communications 381: 602–605.Google Scholar
  32. 32.
    Guzel, A., M. Kanter, A. Guzel, A.F. Yucel, and M. Erboga. 2013. Protective effect of curcumin on acute lung injury induced by intestinal ischaemia/reperfusion. Toxicology and Industrial Health 29: 633–642.Google Scholar
  33. 33.
    Timmers, L., G. Pasterkamp, V.C. de Hoog, F. Arslan, Y. Appelman, and D.P.V. de Kleijn. 2012. The innate immune response in reperfused myocardium. Cardiovascular Research 94: 276–283.Google Scholar
  34. 34.
    Sun, S., G. Zhao, C. Liu, X. Wu, Y. Guo, H. Yu, H. Song, L. Du, S. Jiang, R. Guo, et al. 2013. Inhibition of complement activation alleviates acute lung injury induced by highly pathogenic avian influenza H5N1 virus infection. American Journal of Respiratory Cell and Molecular Biology 49: 221–230.Google Scholar
  35. 35.
    Mao, Y.F., Q.H. Yu, X.F. Zheng, K. Liu, W.Q. Liang, Y.W. Wang, X.M. Deng, and L. Jiang. 2013. Pre-treatment with Cobra venom factor alleviates acute lung injury induced by intestinal ischemia-reperfusion in rats. European Review for Medical and Pharmacological Sciences 17: 2207–2217.Google Scholar
  36. 36.
    Gorsuch, W.B., E. Chrysanthou, W.J. Schwaeble, and G.L. Stahl. 2012. The complement system in ischemia-reperfusion injuries. Immunobiology 217: 1026–1033.Google Scholar
  37. 37.
    Hart, M.L., M.C. Walsh, and G.L. Stahl. 2004. Initiation of complement activation following oxidative stress. In vitro and in vivo observations. Molecular Immunology 41: 165–171.Google Scholar
  38. 38.
    Kew, R.R. 2014. The complement system. Pathobiology of Human Disease, 231–243.Google Scholar
  39. 39.
    Zhang, X., C. Qi, Y. Guo, W. Zhou, and Y. Zhang. 2016. Toll-like receptor 4-related immunostimulatory polysaccharides: primary structure, activity relationships, and possible interaction models. Carbohydrate Polymers 149: 186–206.Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Pharmacology, School of PharmacyFudan UniversityShanghaiChina
  2. 2.Department of Pharmacognosy, School of PharmacyFudan UniversityShanghaiChina

Personalised recommendations