, Volume 40, Issue 3, pp 752–761 | Cite as

Picroside II Protects Rat Lung and A549 Cell Against LPS-Induced Inflammation by the NF-κB Pathway

  • Bingyu Shen
  • Chenxu Zhao
  • Chengzhen Chen
  • Zheng Li
  • Yang Li
  • Ye Tian
  • Haihua FengEmail author


Picroside II is the main active ingredient in the root department of Chinese medicine Picrorhiza scrophulariiflora which has been proved to have beneficial effects on health, such as ameliorating the cerebral ischemia and protecting the liver. However, its effects on acute lung injury remain unclear. The purpose of the study was to evaluate the effects of picroside II on acute lung injury in mice and the inflammation in A549 cells which are lipopolysaccharide (LPS) induced. We evaluated the levels of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1β), and interleukin-6 (IL-6) in vivo and vitro by enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qRT-PCR). Results showed picroside II significantly decreased the concentrations of TNF-α, IL-1β, and IL-6 in cells and mice. In addition, Western blot and immunofluorescence analysis indicated that picroside II suppressed the activation of p65 NF-κB signaling pathway compared with LPS stimulation. In the acute lung injury model of mice, after picroside II treatment, the pathologic changes of lung tissues had been alleviated and lung wet/dry weight ratio was decreased. In summary, picroside II showed the promising effects of anti-inflammation in cells and animals.


picroside II cytokines NF-κB anti-inflammation 



B.Y.S., C.X.Z., C.Z.C., and H.H.F. contributed to the design. B.Y.S., C.X.Z., Z.L., Y.L., and Y.T. did the data collection. B.Y.S., C.X.Z., and H.H.F. did the analysis. B.Y.S. did the writing of the article. C.X.Z., C.Z.C., and H.H.F. did the revisions to the article. This work was supported by grants from the National Nature Science Foundation of China (nos. 31572347 and 31372478).

Compliance with Ethical Standards

All animal experiments were performed in accordance with the National Institutes of Health (NIH) guide for the Care and Use of Laboratory Animals and approved by the Jilin University animal administration committee.

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Gu, J., and C. Korteweg. 2007. Pathology and pathogenesis of severe acute respiratory syndrome. American Journal of Pathology 170: 1136–1147.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Mendez, J.L., and R.D. Hubmayr. 2005. New insights into the pathology of acute respiratory failure. Current Opinion in Critical Care 11(1): 29–36.CrossRefPubMedGoogle Scholar
  3. 3.
    Mei, S.H.J., S.D. McCarter, Y. Deng, C.H. Parker, W.C. Liles, and D.J. Stewart. 2007. Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. PLoS Medicine 4(9): 269.CrossRefGoogle Scholar
  4. 4.
    Berenbaum, F. 2000. Pro-inflammatory cytokines, prostaglandins, and the chondrocyte: mechanisms of intracellular activation. Joint, Bone, Spine 67: 561–564.CrossRefPubMedGoogle Scholar
  5. 5.
    Tousoulis, D., M. Charakida, and C. Stefanadis. 2005. Endothelial function and inflammation in coronary artery disease. Heart 92: 441–444.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Lin, W.W., and M. Karin. 2007. A cytokine-mediated link between innate immunity, inflammation, and cancer. The Journal of Clinical Investigation 117: 1175–1183.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Rubenfeld, G.D., E. Caldwell, E. Peabody, et al. 2005. Incidence and outcomes of acute lung injury. The New England Journal of Medicine 353: 1685–1693.CrossRefPubMedGoogle Scholar
  8. 8.
    Wu, Y., M. Singer, F. Thouron, M. Alaoui-El-Azher, and L. Touqui. 2002. Effect of surfactant on pulmonary expression of type IIA PLA(2) in an animal model of acute lung injury. American Journal of Physiology - Lung Cellular and Molecular Physiology 282(4): 743–750.CrossRefGoogle Scholar
  9. 9.
    Morgan, M.J., and Z.-G. Liu. 2011. Crosstalk of reactive oxygen species and NF-κB signaling. Cell Research 21: 103–115.CrossRefPubMedGoogle Scholar
  10. 10.
    Zabel, U., and P.A. Baeuerle. 1990. Purified human I kappa B can rapidly dissociate the complex of the NF-kappa B transcription factor with its cognate DNA. Cell 61: 255–265.CrossRefPubMedGoogle Scholar
  11. 11.
    Yamaoka, S., G. Courtois, C. Bessia, S.T. Whiteside, R. Weil, F. Agou, H.E. Kirk, R.J. Kay, and A. Israel. 1998. Complementation cloning of NEMO, a component of the IκB kinase complex essential for NF-κB activation. Cell 93: 1231–1240.CrossRefPubMedGoogle Scholar
  12. 12.
    Siomek, A. 2012. NF-κB signaling pathway and free radical impact. Acta Biochimica 59: 323–331.Google Scholar
  13. 13.
    Wang, L., X.H. Liu, H. Chen, and Z.Y. Chen. 2015. Picroside II protects rat kidney against ischemia/reperfusion-induced oxidative stress and inflammation by the TLR4/NF-κB pathway. Experimental and Therapeutic Medcine 9: 1253–1258.Google Scholar
  14. 14.
    Cao, Y., J.W. Liu, Y.J. Yu, P.Y. Zheng, X.D. Zhang, T. Li, and M.C. Guo. 2007. Synergistic protective effect of picroside II and NGF on PC12 cells against oxidative stress induced by H2O2. Pharmacological Reports 59: 573–579.PubMedGoogle Scholar
  15. 15.
    Smit, H.F., B.H. Kroes, A.J. van den Berg, D. van der Wal, E. van den Worm, C.J. Beukelman, H. van Dijk, and R.P. Labadie. 2000. Immunomodulatory and anti-inflammatory activity of Picrorhiza scrophulariiflora. Journal of Ethnopharmacology 73: 101–109.CrossRefPubMedGoogle Scholar
  16. 16.
    He, L.J., M. Liang, F.F. Hou, Z.J. Guo, D. Xie, and X. Zhang. 2009. Ethanol extraction of Picrorhiza scrophulariiflora prevents renal injury in experimental diabetes via anti-inflammation action. Journal of Endocrinology 200: 347–355.CrossRefPubMedGoogle Scholar
  17. 17.
    Li, Q., Z. Li, X.Y. Xu, Y.L. Guo, and F. Du. 2010. Neuroprotective properties of picroside II in a rat model of focal cerebral ischemia. International Journal of Molecular Sciences 11: 4580–4590.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Fenton, M.J., and D.T. Golenbock. 1998. LPS-binding proteins and receptors. Journal of Leukocyte Biology 64(1): 25–32.PubMedGoogle Scholar
  19. 19.
    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.CrossRefPubMedGoogle Scholar
  20. 20.
    Fiorentino, D.F., A. Zlotnik, T.R. Mosmann, M. Howard, and A. O’Garra. 1991. IL-10 inhibits cytokine production by activated macrophages. Journal of Immunology 146: 3444–3451.Google Scholar
  21. 21.
    Ertel, W., M. Keel, U. Steckholzer, M.U. Ungethu, and O. Trentz. 1996. Interleukin-10 attenuates the release of pro-inflammatory cytokines but depresses splenocyte functions in murine endotoxemia. Archives of Surgery 131: 51–56.CrossRefPubMedGoogle Scholar
  22. 22.
    Grutz, G. 2005. New insights into the molecular mechanism of interleukin-10-mediated immunosuppression. Journal of Leukocyte Biology 77: 3–15.PubMedGoogle Scholar
  23. 23.
    Pan, L.L., and M. Dai. 2009. Paeonol from Paeonia suffruticosa prevents TNF-a-induced monocytic cell adhesion to rat aortic endothelial cells by suppression of VCAM-1 expression. Phytomedicine 16: 1027–1032.CrossRefPubMedGoogle Scholar
  24. 24.
    Romics, L., K. Kodys, A. Dolganiuc, L. Graham, A. Velayudham, P. Mandrekar, et al. 2004. Diverse regulation of NF-kappa B and peroxisome proliferator-activated receptors in murine nonalcoholic fatty liver. Hepatology 40: 376–385.CrossRefPubMedGoogle Scholar
  25. 25.
    Choi, Y.H., G.Y. Jin, G.A. Li, and A.H. Yan. 2011. Cornuside suppresses lipopolysaccharide-induced inflammatory mediators by inhibiting nuclear factor-kappa B activation in RAW 264.7 macrophages. Biological & Pharmaceutical Bulletin 34: 959–966.CrossRefGoogle Scholar
  26. 26.
    Li, P., K. Matsunaga, and Y. Ohizumi. 2000. Nerve growth factor-potentiating compounds from Picrorhizae Rhizoma. Biological and Pharmaceutical Bulletin 23: 890–892.CrossRefPubMedGoogle Scholar
  27. 27.
    Epstein, F.H., P.J. Barnes, and M. Karin. 1997. Nuclear factor-κB—a pivotal transcription factor in chronic inflammatory diseases. The New England Journal of Medicine 336: 1066–1071.CrossRefGoogle Scholar
  28. 28.
    Xia, Y.F., B.Q. Ye, Y.D. Li, J.G. Wang, X.J. He, X. Lin, X. Yao, D. Ma, A. Slungaard, R.P. Hebbel, N.S. Key, and J.G. Geng. 2004. Andrographolide attenuates inflammation by inhibition of NF -κB activation through covalent modification of reduced cysteine 62 of p50. Journal of Immunology 173: 4207–4217.CrossRefGoogle Scholar
  29. 29.
    Ghosh, S., M.J. May, and E.B. Kopp. 1998. NF-κB and Rel proteins:evolutionarily conserved mediators of immune responses. Annual Review of Immunology 16: 225–260.CrossRefPubMedGoogle Scholar
  30. 30.
    Li, Q., and I.M. Verma. 2002. NF-κB regulation in the immune system. Nature Reviews Immunology 10: 725–734.CrossRefGoogle Scholar
  31. 31.
    Duan, Y., J. Learoyd, A.Y. Meliton, A.R. Leff, and X. Zhu. 2012. Inhibition of Pyk2 blocks lung inflammation and injury in a mouse model of acute lung injury. Respiratory Research 13: 4.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Klebanoff, S.J. 2005. Myeloperoxidase: friend and foe. Journal of Leukocyte Biology 77(5): 598–625.CrossRefPubMedGoogle Scholar
  33. 33.
    Razavi, H.M., F. le Wang, S. Weicker, M. Rohan, C. Law, D.G. McCormack, et al. 2004. Pulmonary neutrophil infiltration in murine sepsis: role of inducible nitric oxide synthase. American Journal of Respiratory and Critical Care Medicine 170(3): 227–233.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Bingyu Shen
    • 1
  • Chenxu Zhao
    • 1
  • Chengzhen Chen
    • 2
  • Zheng Li
    • 1
  • Yang Li
    • 1
  • Ye Tian
    • 1
  • Haihua Feng
    • 1
    Email author
  1. 1.Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary MedicineJilin UniversityChangchunPeople’s Republic of China
  2. 2.Laboratory Animal CenterJilin UniversityChangchunPeople’s Republic of China

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