Skip to main content

Advertisement

SpringerLink
Log in

Protective Effects of Asiatic Acid Against Spinal Cord Injury-Induced Acute Lung Injury in Rats

  • ORIGINAL ARTICLE
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

The biological effects of asiatic acid (AA) on spinal cord injury (SCI)-induced acute lung injury (ALI) have not been investigated. We aimed to investigate the therapeutic efficacy and molecular mechanisms of AA on SCI-induced ALI. One-hundred and fifty Sprague–Dawley rats were randomly assigned to five groups: sham, SCI, SCI + dexamethasone (Dex, 2 mg/kg), SCI + AA (30 mg/kg), and SCI + AA (75 mg/kg). The influences of AA on histologic changes, pulmonary edema, neutrophil infiltration and activation, proinflammatory cytokine production, oxidative stress, and Nrf2 and NLRP3 inflammasome protein expression were estimated. AA administration at the 30- and 75-mg/kg doses significantly attenuates lung wet-to-dry weight (W/D) ratio, pulmonary permeability index (PPI), and pulmonary histologic conditions. Furthermore, the protective effects of AA might be attributed to the reduction of neutrophil infiltration, myeloperoxidase (MPO), inflammatory cytokines, reactive oxygen species (ROS), malondialdehyde (MDA), and the increase of superoxide dismutase (SOD) and catalase (CAT). Moreover, AA markedly upregulated Nrf2 levels and downregulated NLRP3 inflammasome protein expression in lung tissues. AA exhibits a protective effect on SCI-induced ALI by alleviating the inflammatory response, by inhibiting NLRP3 inflammasome activation and oxidative stress with the upregulation of Nrf2 protein levels. The use of AA may be a potential efficient therapeutic strategy for the treatment of SCI-induced ALI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Bao, F., A. Brown, G.A. Dekaban, V. Omana, and L.C. Weaver. 2011. CD11d integrin blockade reduces the systemic inflammatory response syndrome after spinal cord injury. Experimental Neurology 231: 272–283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Liu, J., L. Yi, Z. Xiang, J. Zhong, H. Zhang, and T. Sun. 2015. Resveratrol attenuates spinal cord injury-induced inflammatory damage in rat lungs. International Journal of Clinical and Experimental Pathology 8: 1237–1246.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Tao, W., Q. Su, H. Wang, S. Guo, Y. Chen, J. Duan, et al. 2015. Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro. International Immunopharmacology 27: 138–147.

    Article  CAS  PubMed  Google Scholar 

  4. Yeh, C.H., J.J. Yang, M.L. Yang, Y.C. Li, and Y.H. Kuan. 2014. Rutin decreases lipopolysaccharide-induced acute lung injury via inhibition of oxidative stress and the MAPK-NF-kB pathway. Free Radical Biology and Medicine 69: 249–257.

    Article  CAS  PubMed  Google Scholar 

  5. Zhong, W., Y. Cui, Q. Yu, X. Xie, Y. Liu, M. Wei, et al. 2014. Modulation of LPS stimulated pulmonary inflammation by Borneol in murine acute lung injury model. Inflammation 37: 1148–1157.

    Article  CAS  PubMed  Google Scholar 

  6. Chen, T., Y. Mou, J. Tan, L. Wei, Y. Qiao, T. Wei, et al. 2015. The protective effect of CDDO-Me on lipopolysaccharide-induced acute lung injury in mice. International Immunopharmacology 25: 55–64.

    Article  CAS  PubMed  Google Scholar 

  7. Pratheeshkumar, P., Y.O. Son, S.P. Divya, R.V. Roy, J.A. Hitron, L. Wang, et al. 2014. Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways. Toxicology and Applied Pharmacology 281: 230–241.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ávila, L.C., T.R. Bruggemann, F. Bobinski, M.D. da Silva, R.C. Oliveira, D.F. Martins, et al. 2015. Effects of High-Intensity Swimming on Lung Inflammation and Oxidative Stress in a Murine Model of DEP-Induced Injury. PLoS One 10: e0137273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Abiko, Y., M. Mizokawa, and Y. Kumagai. 2014. Activation of the Kelch-like ECH-associated protein 1 (Keap1)/NF-E2-related factor 2 (Nrf2) pathway through covalent modification of the 2-alkenal group of aliphatic electrophiles in Coriandrum sativum L. Journal of Agricultural and Food Chemistry 62: 10936–10944.

    Article  CAS  PubMed  Google Scholar 

  10. Zhou, R., A. Tardivel, B. Thorens, I. Choi, and J. Tschopp. 2010. Thioredoxin- interacting protein links oxidative stress to inflammasome activation. Nature Immunology 11: 136–140.

    Article  CAS  PubMed  Google Scholar 

  11. Yan, Y., W. Jiang, L. Liu, X. Wang, C. Ding, Z. Tian, et al. 2015. Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome. Cell 160: 62–73.

    Article  CAS  PubMed  Google Scholar 

  12. Lamkanfi, M., and V.M. Dixit. 2012. Inflammasomes and their roles in health and disease. Annual Review of Cell and Developmental Biology 28: 137–161.

    Article  CAS  PubMed  Google Scholar 

  13. Han, S., W. Cai, X. Yang, Y. Jia, Z. Zheng, H. Wang, et al. 2015. ROS-Mediated NLRP3 Inflammasome Activity Is Essential for Burn-Induced Acute Lung Injury. Mediators of Inflammation 2015: 720457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tsao, S.M., and M.C. Yin. 2015. Antioxidative and antiinflammatory activities of asiatic acid, glycyrrhizic acid, and oleanolic acid in human bronchial epithelial cells. Journal of Agricultural and Food Chemistry 63: 3196–3204.

    Article  CAS  PubMed  Google Scholar 

  15. Pakdeechote, P., S. Bunbupha, U. Kukongviriyapan, P. Prachaney, W. Khrisanapant, and V. Kukongviriyapan. 2014. Asiatic acid alleviates hemodynamic and metabolic alterations via restoring eNOS/iNOS expression, oxidative stress, and inflammation in diet-induced metabolic syndrome rats. Nutrients 6: 355–370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Guo, W., W. Liu, B. Jin, J. Geng, J. Li, H. Ding, et al. 2015. Asiatic acid ameliorates dextran sulfate sodium-induced murine experimental colitis via suppressing mitochondria-mediated NLRP3 inflammasome activation. International Immunopharmacology 24: 232–238.

    Article  CAS  PubMed  Google Scholar 

  17. Krishnamurthy, R.G., M.C. Senut, D. Zemke, J. Min, M.B. Frenkel, E.J. Greenberg, et al. 2009. Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia. Journal of Neuroscience Research 87: 2541–2550.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bunbupha, S., P. Prachaney, U. Kukongviriyapan, V. Kukongviriyapan, J.U. Welbat, and P. Pakdeechote. 2015. Asiatic acid alleviates cardiovascular remodelling in rats with L-NAME-induced hypertension. Clinical and Experimental Pharmacology and Physiology 42: 1189–1197.

    Article  CAS  PubMed  Google Scholar 

  19. Young, W. 2002. Spinal cord contusion models. Progress in Brain Research 137: 231–255.

    Article  PubMed  Google Scholar 

  20. Gan, L., J. Zhong, R. Zhang, T. Sun, Q. Li, X. Chen, et al. 2015. The Immediate Intramedullary Nailing Surgery Increased the Mitochondrial DNA Release That Aggravated Systemic Inflammatory Response and Lung Injury Induced by Elderly Hip Fracture. Mediators of Inflammation 2015: 587378.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gao, J., L. Zhou, Y. Ge, S. Lin, and J. Du. 2013. Effects of different resuscitation fluids on pulmonary expression of aquaporin1 and aquaporin5 in a rat model of uncontrolled hemorrhagic shock and infection. PLoS One 8: e64390.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lee, K.Y., O.N. Bae, K. Serfozo, S. Hejabian, A. Moussa, M. Reeves, et al. 2012. Asiatic acid attenuates infarct volume, mitochondrial dysfunction, and matrix metalloproteinase-9 induction after focal cerebral ischemia. Stroke 43: 1632–1638.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gao, J., J. Chen, X. Tang, L. Pan, F. Fang, L. Xu, et al. 2006. Mechanism underlying mitochondrial protection of asiatic acid against hepatotoxicity in mice. Journal of Pharmacy and Pharmacology 58: 227–233.

    Article  CAS  PubMed  Google Scholar 

  24. Abraham, E. 2003. Neutrophils and acute lung injury. Critical Care Medicine 31: S195–9.

    Article  PubMed  Google Scholar 

  25. Hirano, Y., M. Aziz, W.L. Yang, Z. Wang, M. Zhou, M. Ochani, et al. 2015. Neutralization of osteopontin attenuates neutrophil migration in sepsis-induced acute lung injury. Critical Care 19: 53.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Uriarte, S.M., M.J. Rane, M.L. Merchant, S. Jin, A.B. Lentsch, R.A. Ward, et al. 2013. Inhibition of neutrophil exocytosis ameliorates acute lung injury in rats. Shock 39: 286–292.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ma, H.J., X.L. Huang, Y. Liu, and Y.M. Fan. 2012. Sulfur dioxide attenuates LPS-induced acute lung injury via enhancing polymorphonuclear neutrophil apoptosis. Acta Pharmacologica Sinica 33: 983–990.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kolliputi, N., L. Galam, P.T. Parthasarathy, S.M. Tipparaju, and R.F. Lockey. 2012. NALP-3 inflammasome silencing attenuates ceramide-induced transepithelial permeability. Journal of Cellular Physiology 227: 3310–3316.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Liu, Z., H. Zhao, W. Liu, T. Li, Y. Wang, and M. Zhao. 2015. NLRP3 inflammasome activation is essential for paraquat-induced acute lung injury. Inflammation 38: 433–444.

    Article  CAS  PubMed  Google Scholar 

  30. Ganter, M.T., J. Roux, B. Miyazawa, M. Howard, J.A. Frank, G. Su, et al. 2008. Interleukin-1beta causes acute lung injury via alphavbeta5 and alphavbeta6 integrin-dependent mechanisms. Circulation Research 102: 804–812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ortiz, L.A., M. Dutreil, C. Fattman, A.C. Pandey, G. Torres, K. Go, et al. 2007. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci U SA 104: 11002–11007.

    Article  CAS  Google Scholar 

  32. Jones, H.D., T.R. Crother, R.A. Gonzalez-Villalobos, M. Jupelli, S. Chen, J. Dagvadorj, et al. 2014. The NLRP3 inflammasome is required for the development of hypoxemia in LPS/mechanical ventilation acute lung injury. American Journal of Respiratory Cell and Molecular Biology 50: 270–280.

    PubMed  PubMed Central  Google Scholar 

  33. Herold, S., T.S. Tabar, H. Janssen, K. Hoegner, M. Cabanski, P. Lewe-Schlosser, et al. 2011. Exudate macrophages attenuate lung injury by the release of IL-1 receptor antagonist in gram-negative pneumonia. American Journal of Respiratory and Critical Care Medicine 183: 1380–1390.

    Article  CAS  PubMed  Google Scholar 

  34. Hoshino, T., M. Okamoto, Y. Sakazaki, S. Kato, H.A. Young, and H. Aizawa. 2009. Role of proinflammatory cytokines IL-18 and IL-1beta in bleomycin-induced lung injury in humans and mice. American Journal of Respiratory Cell and Molecular Biology 41: 661–670.

    Article  CAS  PubMed  Google Scholar 

  35. Tang, M., Y. Tian, D. Li, J. Lv, Q. Li, C. Kuang, et al. 2014. TNF-α mediated increase of HIF-1α inhibits VASP expression, which reduces alveolar-capillary barrier function during acute lung injury (ALI). PLoS One 9: e102967.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gao, M., B. Xie, C. Gu, H. Li, F. Zhang, and Y. Yu. 2015. Targeting the proinflammatory cytokine tumor necrosis factor-α to alleviate cardiopulmonary bypass-induced lung injury (review). Molecular Medicine Reports 11: 2373–2378.

    CAS  PubMed  Google Scholar 

  37. Yu, Y., M. Gao, H. Li, F. Zhang, and C. Gu. 2013. Pulmonary artery perfusion with anti-tumor necrosis factor alpha antibody reduces cardiopulmonary bypass-induced inflammatory lung injury in a rabbit model. PLoS One 8: e83236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Liu, X.Y., C.Y. Li, H. Bu, Z. Li, B. Li, M.M. Sun, et al. 2008. The neuroprotective potential of phase II enzyme inducer on motor neuron survival in traumatic spinal cord injury in vitro. Cellular and Molecular Neurobiology 28: 769–779.

    Article  CAS  PubMed  Google Scholar 

  39. Mao, L., H. Wang, L. Qiao, and X. Wang. 2010. Disruption of Nrf2 enhances the upregulation of nuclear factor-kappaB activity, tumor necrosis factor-alpha, and matrix metalloproteinase-9 after spinal cord injury in mice. Mediators of Inflammation 2010: 238321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Luo, Y.P., L. Jiang, K. Kang, D.S. Fei, X.L. Meng, C.C. Nan, et al. 2014. Hemin inhibits NLRP3 inflammasome activation in sepsis-induced acute lung injury, involving heme oxygenase-1. International Immunopharmacology 20: 24–32.

    Article  CAS  PubMed  Google Scholar 

  41. Gürer, B., H. Kertmen, E. Kasim, E.R. Yilmaz, B.H. Kanat, M.F. Sargon, et al. 2015. Neuroprotective effects of testosterone on ischemia/reperfusion injury of the rabbit spinal cord. Injury 46: 240–248.

    Article  PubMed  Google Scholar 

  42. Jing, W., M. Chunhua, and W. Shumin. 2015. Effects of acteoside on lipopolysaccharideinduced inflammation in acute lung injury via regulation of NF-kappaB pathway in vivo and in vitro. Toxicology and Applied Pharmacology 285: 128–135.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Traditional Chinese Medicine Science and Technology Project of Zhejiang (grant no. 2011ZA078).

Author information

Authors and Affiliations

  1. Department of Orthopedics, Hangzhou First People’s Hospital,Nanjing Medical University, No. 261 Huansha Road, Shangcheng District, Hangzhou, 310006, China

    Wu Jiang, Maoqiang Li, Fan He, Wangxiang Yao, Zhenyu Bian, Xuepeng Wang & Liulong Zhu

Authors
  1. Wu Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maoqiang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fan He
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wangxiang Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhenyu Bian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xuepeng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Liulong Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Liulong Zhu.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, W., Li, M., He, F. et al. Protective Effects of Asiatic Acid Against Spinal Cord Injury-Induced Acute Lung Injury in Rats. Inflammation 39, 1853–1861 (2016). https://doi.org/10.1007/s10753-016-0414-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-016-0414-3

KEY WORDS

Search

Navigation