Skip to main content
Log in

Suppression of P2X7/NF-κB pathways by Schisandrin B contributes to attenuation of lipopolysaccharide-induced inflammatory responses in acute lung injury

  • Research Article
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

The aim of the present study was to assess the effects and mechanisms of Schisandrin B (SchB) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg), and SchB (25, 50, and 75 mg/kg) was injected 1 h before LPS challenge by gavage. After 12 h, bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected. Histological studies demonstrated that SchB attenuated LPS-induced interstitial edema, hemorrhage, and infiltration of neutrophils in the lung tissue. SchB pretreatment at doses of 25, 50, and 75 mg/kg was shown to reduce LPS-induced lung wet-to-dry weight ratio and lung myeloperoxidase activity. In addition, pretreatment with SchB lowered the number of inflammatory cells and pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in BALF. The mRNA and protein expression levels of nuclear factor kappa B (NF-κB) signaling-related molecules activated by P2X7 were investigated to determine the molecular mechanism of SchB. The findings presented here suggest that the protective mechanism of SchB may be attributed partly to the decreased production of pro-inflammatory cytokines through the inhibition of P2X7/NF-κB activation.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

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

Similar content being viewed by others

References

  • Bönig H, Packeisen J, Röhne B, Hempel L, Hannen M, Klein-Vehne A, Burdach S, Körholz D (1998) Interaction between interleukin 10 and interleukin 6 in human B-cell differentiation. Immunol Investig 27:267–280

    Article  Google Scholar 

  • Chang X, He H, Zhu L, Gao J, Wei T, Ma Z, Yan T (2015) Protective effect of apigenin on Freund’s complete adjuvant-induced arthritis in rats via inhibiting P2X7/NF-κB pathway. Chem Biol Interact 236:41–46

    Article  CAS  PubMed  Google Scholar 

  • Chatterjee S, Das S (2015) P2X7 receptor as a key player in oxidative stress-driven cell fate in nonalcoholic steatohepatitis. Oxid Med Cell Longev 2015:172493

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen N, Ko M (2010) Schisandrin B-induced glutathione antioxidant response and cardioprotection are mediated by reactive oxidant species production in rat hearts. Biol Pharm Bull 33:825–829

    Article  CAS  PubMed  Google Scholar 

  • Cribbs SK, Martin GS (2009) Fluid balance and colloid osmotic pressure in acute respiratory failure: optimizing therapy. Expert Rev Respir Med 3:651–662

    Article  PubMed  Google Scholar 

  • Eltom S, Stevenson CS, Rastrick J, Dale N, Raemdonck K, Wong S, Catley MC, Belvisi MG, Birrell MA (2011) P2X7 receptor and caspase 1activation are central to airway inflammation observed after exposure to tobacco smoke. PLoS One 6:e24097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng G, Jiang ZY, Sun B, Fu J, Li TZ (2015) Fisetin alleviates lipopolysaccharide-induced acute lung injury via TLR4-mediated NF-κB signaling pathway in rats. Inflammation. doi:10.1007/s10753-015-0233-y

    Google Scholar 

  • Gubert C, Fries GR, Pfaffenseller B, Ferrari P, Coutinho-Silva R, Morrone FB, Kapczinski F, Battastini AM (2014) Role of P2X7 receptor in an animal model of mania induced by d-amphetamine. Mol Neurobiol. doi:10.1007/s12035-014-9031-z

    PubMed  Google Scholar 

  • Hughes JP, Hatcher JP, Chessell IP (2007) The role of P2X7 in pain and inflammation. Purinergic Signal 3:163–169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jing W, Chunhua M, Shumin W (2015) Effects of acteoside on lipopolysaccharide-induced inflammation in acute lung injury via regulation of NF-κB pathway in vivo and in vitro. Toxicol Appl Pharmacol 285:128–135

    Article  CAS  PubMed  Google Scholar 

  • Li JW, Wu X (2015) Mesenchymal stem cells ameliorate LPS-induced acute lung injury through KGF promoting alveolar fluid clearance of alveolar type II cells. Eur Rev Med Pharmacol Sci 19:2368–2378

    PubMed  Google Scholar 

  • Li W, Qiu X, Jiang H, Zhi Y, Fu J, Liu J (2015) Ulinastatin inhibits the inflammation of LPS-induced acute lung injury in mice via regulation of AMPK/NF-κB pathway. Int Immunopharmacol. doi:10.1016/j.intimp.2015.09.028

    Google Scholar 

  • Liu Y, Xiao Y, Li Z (2011) P2X7 receptor positively regulates MyD88-dependent NF-κB activation. Cytokine 55:229–236

    Article  CAS  PubMed  Google Scholar 

  • Lucattelli M, Cicko S, Müller T, Lommatzsch M, De Cunto CG, Cardini S, Sundas W, Grimm M, Zeiser R, Dürk T, Zissel G (2011) P2X7 receptor signaling in the pathogenesis of smoke-induced lung inflammation and emphysema. Am J Respir Cell Mol Biol 44:423–429

    Article  CAS  PubMed  Google Scholar 

  • Lv XJ, Zhao LJ, Hao YQ, Su ZZ, Li JY, Du YW (2015) Schisandrin B inhibits the proliferation of human lung adenocarcinoma A549 cells by inducing cycle arrest and apoptosis. Int J Clin Exp Med 8:6926–6936

    PubMed  PubMed Central  Google Scholar 

  • Ma C, Zhu L, Wang J, He H, Chang X, Gao J, Shumin W, Yan T (2015) Anti-inflammatory effects of water extract of Taraxacum mongolicum hand.-Mazz on lipopolysaccharide-induced inflammation in acute lung injury by suppressing PI3 K/Akt/mTOR signaling pathway. J Ethnopharmacol 168:349–355

    Article  PubMed  Google Scholar 

  • McInnes IB, Cruwys S, Bowers K, Braddock M (2014) Targeting the P2X7 receptor in rheumatoid arthritis: biological rationale for P2X7 antagonism. Clin Exp Rheumatol 32:878–882

    PubMed  Google Scholar 

  • Poroyko V, Meng F, Meliton A, Afonyushkin T, Ulanov A, Semenyuk E, Latif O, Tesic V, Birukova AA, Birukov KG (2015) Alterations of lung microbiota in a mouse model of LPS-induced lung injury. Am J Physiol Lung Cell Mol Physiol 309:L76–L83

    Article  CAS  PubMed  Google Scholar 

  • Thandavarayan RA, Giridharan VV, Arumugam S, Suzuki K, Ko KM, Krishnamurthy P, Watanabe K, Konishi T (2015) Schisandrin B prevents doxorubicin induced cardiac dysfunction by modulation of DNA damage, oxidative stress and inflammation through inhibition of MAPK/p53 signaling. PLoS One 10:e0119214

    Article  PubMed  PubMed Central  Google Scholar 

  • Vladimir L, Stephen AR, Alistair GR, Daniel EZ, Kathleen AK, Aaron EL, Matti N, Ilya S, Alan A (2009) Role of the transcription factor C/EBPδ in a regulatory circuit that discriminates between transient and persistent toll-like receptor 4-induced signals. Nat Immunol 10:437–443

    Google Scholar 

  • Xing J, Yakubov B, Poroyko V, Birukova AA (2012) Opposite effects of ANP receptors in attenuation of LPS-induced endothelial permeability and lung injury. Microvasc Res 83:194–199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was supported in parts by grants from the Nanjing medical university, China. The authors gratefully acknowledge associate Professor Su Ning for her assistance in histopathological analysis.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hongliang Bian.

Ethics declarations

Conflict of interest

Authors declare that they have no competing interests.

Additional information

Zhiyong Cai and Jindi Liu have contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cai, Z., Liu, J., Bian, H. et al. Suppression of P2X7/NF-κB pathways by Schisandrin B contributes to attenuation of lipopolysaccharide-induced inflammatory responses in acute lung injury. Arch. Pharm. Res. 39, 499–507 (2016). https://doi.org/10.1007/s12272-016-0713-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-016-0713-0

Keywords

Navigation