Skip to main content

Advertisement

Log in

Paeoniflorin protects against lipopolysaccharide-induced acute lung injury in mice by alleviating inflammatory cell infiltration and microvascular permeability

  • Original Research Paper
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective

The present study aims to explore the effects of paeoniflorin (PF), a monoterpene glycoside isolated from the roots of Paeonia lactiflora Pallas, on acute lung injury (ALI) and the possible mechanisms.

Materials and method

ALI was induced in mice by an intratracheal instillation of lipopolysaccharide (LPS, 1 mg/kg), and PF was injected intraperitoneally 30 min prior to LPS administration. After 24 h, lung water content, histology, microvascular permeability and proinflammatory cytokines in the bronchoaveolar lavage fluid were evaluated.

Results

It was shown that PF (50, 100 mg/kg) could alleviate LPS-induced ALI, evidenced by reduced pulmonary edema, improved histological changes, and attenuated inflammatory cell accumulation in the interstitium and alveolar space as well as microvascular permeability. It also markedly down-regulated the expressions of proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α at both transcription and protein levels. Additionally, PF inhibited the phosphorylations of p38 MAP kinase (p38) and c-Jun NH2-terminal kinase (JNK) but not extracellular signal-regulated kinase (ERK), and prevented the activation of nuclear factor-kappa B (NF-κB) in the lung tissues.

Conclusion

The findings suggest that PF is able to alleviate ALI, and the underlying mechanisms are probably attributed to decreasing the production of proinflammatory cytokines through down-regulation of the activation of p38, JNK and NF-κB pathways in lung tissues.

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

  1. Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, et al. Incidence and outcomes of acute lung injury. N Engl J Med. 2005;353:1685–93.

    Article  PubMed  CAS  Google Scholar 

  2. Reutershan J, Cagnina RE, Chang D, Linden J, Ley K. Therapeutic anti-inflammatory effects of myeloid cell adenosine receptor A2a stimulation in lipopolysaccharide-induced lung injury. J Immunol. 2007;179:1254–63.

    PubMed  CAS  Google Scholar 

  3. Ngamsri KC, Wagner R, Vollmer I, Stark S, Reutershan J. Adenosine receptor A1 regulates polymorphonuclear cell trafficking and microvascular permeability in lipopolysaccharide-induced lung injury. J Immunol. 2010;185:4374–84.

    Article  PubMed  CAS  Google Scholar 

  4. Reutershan J, Basit A, Galkina EV, Ley K. Sequential recruitment of neutrophils into lung and bronchoalveolar lavage fluid in LPS-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2005;289:L807–15.

    Article  PubMed  CAS  Google Scholar 

  5. Petty JM, Sueblinvong V, Lenox CC, Jones CC, Cosgrove GP, Cool CD, et al. Pulmonary stromal-derived factor-1 expression and effect on neutrophil recruitment during acute lung injury. J Immunol. 2007;178:8148–57.

    PubMed  CAS  Google Scholar 

  6. Jain R, DalNogare A. Pharmacological therapy for acute respiratory distress syndrome. Mayo Clin Proc. 2006;81:205–12.

    Article  PubMed  CAS  Google Scholar 

  7. Lee B, Shin YW, Bae EA, Han SJ, Kim JS, Kang SS, et al. Antiallergic effect of the root of Paeonia lactiflora and its constituents paeoniflorin and paeonol. Arch Pharm Res. 2008;31:445–50.

    Article  PubMed  CAS  Google Scholar 

  8. Zheng YQ, Wei W, Zhu L, Liu JX. Effects and mechanisms of Paeoniflorin, a bioactive glucoside from paeony root, on adjuvant arthritis in rats. Inflamm Res. 2007;56:182–8.

    Article  PubMed  CAS  Google Scholar 

  9. Liu DF, Wei W, Song LH. Protective effect of paeoniflorin on immunological liver injury induced by bacillus Calmette-Guerin plus lipopolysaccharide: modulation of tumour necrosis factor-alpha and interleukin-6 MRNA. Clin Exp Pharmacol Physiol. 2006;33:332–9.

    Article  PubMed  CAS  Google Scholar 

  10. Yu HY, Liu MG, Liu DN, Shang GW, Wang Y, Qi C, et al. Antinociceptive effects of systemic paeoniflorin on bee venom-induced various ‘phenotypes’ of nociception and hypersensitivity. Pharmacol Biochem Behav. 2007;88:131–40.

    Article  PubMed  CAS  Google Scholar 

  11. Jiang WL, Chen XG, Zhu HB, Gao YB, Tian JW, Fu FH. Paeoniflorin inhibits systemic inflammation and improves survival in experimental sepsis. Basic Clin Pharmacol Toxicol. 2009;105:64–71.

    Article  PubMed  CAS  Google Scholar 

  12. Kim ID, Ha BJ. The effects of paeoniflorin on LPS-induced liver inflammatory reactions. Arch Pharm Res. 2010;33:959–66.

    Article  PubMed  CAS  Google Scholar 

  13. Xu H, Gao XH, Song J, Wang FY, Xu Z, Lu D, et al. Peoniflorin prevents the adhesion between inflammatory endothelial cells and leukocytes through inhibiting the activation of MAPKs and NF-κB. Drug Dev Res. 2010;71:275–84.

    Article  CAS  Google Scholar 

  14. Zhang XJ, Chen HL, Li Z, Zhang HQ, Xu HX, Sung JJ, et al. Analgesic effect of paeoniflorin in rats with neonatal maternal separation-induced visceral hyperalgesia is mediated through adenosine A(1) receptor by inhibiting the extracellular signal-regulated protein kinase (ERK) pathway. Pharmacol Biochem Behav. 2009;94:88–97.

    Article  PubMed  CAS  Google Scholar 

  15. Liu HQ, Zhang WY, Luo XT, Ye Y, Zhu XZ. Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease by activation of adenosine A1 receptor. Br J Pharmacol. 2006;148:314–25.

    Article  PubMed  CAS  Google Scholar 

  16. Tsuruta Y, Park YJ, Siegal GP, Liu G, Abraham E. Involvement of vitronectin in lipopolysaccaride-induced acute lung injury. J Immunol. 2007;179:7079–86.

    PubMed  CAS  Google Scholar 

  17. Jacobson JR, Barnard JW, Grigoryev DN, Ma SH, Tuder RM, Garcia JGN. Simvastatin attenuates vascular leak and inflammation in murine inflammatory lung injury. Am J Physiol Lung Cell Mol Physiol. 2005;288:L1026–32.

    Article  PubMed  CAS  Google Scholar 

  18. Zhang XM, Song KJ, Xiong HZ, Li HY, Chu X, Deng XM. Protective effect of florfenicol on acute lung injury induced by lipopolysaccharide in mice. Int Immunopharmacol. 2009;9:1525–9.

    Article  PubMed  CAS  Google Scholar 

  19. Tan ZH, Yu LH, Wei HL, Liu GT. Scutellarin protects against lipopolysaccharide-induced acute lung injury via inhibition of NF-kappaB activation in mice. J Asian Nat Prod Res. 2010;12:175–84.

    Article  PubMed  CAS  Google Scholar 

  20. Liu S, Feng G, Wang GL, Liu GJ. p38MAPK inhibition attenuates LPS-induced acute lung injury involvement of NF-kappaB pathway. Eur J Pharmacol. 2008;584:159–65.

    Article  PubMed  CAS  Google Scholar 

  21. Matute-Bello G, Frevert CW, Martin TR. Animal models of acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2008;295:L379–99.

    Article  PubMed  CAS  Google Scholar 

  22. Tumurkhuu G, Koide N, Dagvadorj J, Morikawa A, Hassan F, Islam S, et al. The mechanism of development of acute lung injury in lethal endotoxic shock using alpha-galactosylceramide sensitization. Clin Exp Immunol. 2008;152:182–91.

    Article  PubMed  CAS  Google Scholar 

  23. Wang HD, Lu DX, Qi RB. Therapeutic strategies targeting the LPS signaling and cytokines. Pathophysiology. 2009;16:291–6.

    Article  PubMed  CAS  Google Scholar 

  24. Liaudet L, Mabley JG, Pacher P, Virág L, Soriano FG, Marton A, et al. Inosine exerts a broad range of antiinflammatory effects in a murine model of acute lung injury. Ann Surg. 2002;235:568–78.

    Article  PubMed  Google Scholar 

  25. Sato K, Kadiiska MB, Ghio AJ, Corbett J, Fann YC, Holland SM, et al. In vivo lipid-derived free radical formation by NADPH oxidase in acute lung injury induced by lipopolysaccharide: a model for ARDS. FASEB J. 2002;16:1713–20.

    Article  PubMed  CAS  Google Scholar 

  26. Asti C, Ruggieri V, Porzio S, Chiusaroli R, Melillo G, Caselli GF. Lipopolysaccharide-induced lung injury in mice. I. Concomitant evaluation of inflammatory cells and haemorrhagic lung damage. Pulm Pharmacol Ther. 2000;13:61–9.

    Article  PubMed  CAS  Google Scholar 

  27. Szarka RJ, Wang N, Gordon L, Nation PN, Smith RH. A murine model of pulmonary damage induced by lipopolysaccharide via intranasal instillation. J Immunol Methods. 1997;202:49–57.

    Article  PubMed  CAS  Google Scholar 

  28. Camp SM, Bittman R, Chiang ET, Moreno-Vinasco L, Mirzapoiazova T, Sammani S, et al. Synthetic analogs of FTY720 [2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol] differentially regulate pulmonary vascular permeability in vivo and in vitro. J Pharmacol Exp Ther. 2009;331:54–64.

    Article  PubMed  CAS  Google Scholar 

  29. Bhatia M, Moochhala S. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol. 2004;202:145–56.

    Article  PubMed  CAS  Google Scholar 

  30. Park WY, Goodman RB, Steinberg KP, Ruzinski JT, Radella F 2nd, Park DR, et al. Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001;164:1896–903.

    PubMed  CAS  Google Scholar 

  31. Ganter MT, Roux J, Miyazawa B, Howard M, Frank JA, Su G, et al. Interleukin-1beta causes acute lung injury via alphavbeta5 and alphavbeta6 integrin-dependent mechanisms. Circ Res. 2008;102:804–12.

    Article  PubMed  CAS  Google Scholar 

  32. Cao WJ, Zhang W, Liu JJ, Wang Y, Peng XM, Lu DX, et al. Paeoniflorin improves survival in LPS-challenged mice through the suppression of TNF-α and IL-1β release and augmentation of IL-10 production. Int Immunopharmacol. 2011;11:172–8.

    Article  PubMed  CAS  Google Scholar 

  33. Walley KR, McDonald TE, Higashimoto Y, Hayashi S. Modulation of proinflammatory cytokines by nitric oxide in murine acute lung injury. Am J Respir Crit Care Med. 1999;160:698–704.

    PubMed  CAS  Google Scholar 

  34. Mehta S. The effects of nitric oxide in acute lung injury. Vasc Pharmacol. 2005;43:390–403.

    Article  CAS  Google Scholar 

  35. Wang LF, Patel M, Razavi HM, Weicker S, Joseph MG, McCormack DG, et al. Role of inducible nitric oxide synthase in pulmonary microvascular protein leak in murine sepsis. Am J Respir Crit Care Med. 2002;165:1634–9.

    Article  Google Scholar 

  36. Mikawa K, Nishina K, Takao Y, Obara H. ONO-1714, a nitric oxide synthase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits. Anesth Analg. 2003;97:1751–5.

    Article  PubMed  CAS  Google Scholar 

  37. Yoshihisa Y, Furuichi M, Urrehman M, Ueda C, Makino T, Shimizu T. The traditional Japanese formula keishibukuryogan inhibits the production of inflammatory cytokines by dermal endothelial cells. Mediat Inflamm. 2010;2010:1–8.

    Article  Google Scholar 

  38. Sun Y, Dong Y, Jiang HJ, Cai TT, Chen L, Zhou X, et al. Dissection of the role of paeoniflorin in the traditional Chinese medicinal formula Si-Ni-San against contact dermatitis in mice. Life Sci. 2009;84:337–44.

    Article  PubMed  CAS  Google Scholar 

  39. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140:805–20.

    Article  PubMed  CAS  Google Scholar 

  40. Kim HJ, Lee HS, Chong YH, Kang JL. p38 Mitogen-activated protein kinase up-regulates LPS-induced NF-kappaB activation in the development of lung injury and RAW 264.7 macrophages. Toxicology. 2006;225:36–47.

    Article  PubMed  CAS  Google Scholar 

  41. Schuh K, Pahl A. Inhibition of the MAP kinase ERK protects from lipopolysaccharide-induced lung injury. Biochem Pharmacol. 2009;77:1827–34.

    Article  PubMed  CAS  Google Scholar 

  42. Chen T, Guo ZP, Jiao XY, Jia RZ, Zhang YH, Li JY, et al. Paeoniflorin suppresses tumor necrosis factor-α induced chemokineproduction in human dermal microvascular endothelial cells by blocking nuclear factor-κB and ERK pathway. Arch Dermatol Res. 2011; 303:351-360.

    Google Scholar 

  43. Baeuerle PA, Baltimore D. NF-kappa B: ten years after. Cell. 1996;87:13–20.

    Article  PubMed  CAS  Google Scholar 

  44. Jin L, Zhang LM, Xie KQ, Ye Y, Feng L. Paeoniflorin suppresses the expression of ICAM-1 in endotoxin-treated human monocytic cells. Br J Pharmacol. 2011. doi:10.1111/j.1476-5381.2011.01464.x.

  45. Wu H, Li W, Wang T, Shu Y, Liu P. Paeoniflorin suppress NF-kappaB activation through modulation of I kappaB alpha and enhances 5-fluorouracil-induced apoptosis in human gastric carcinoma cells. Biomed Pharmacother. 2008;62:659–66.

    Article  PubMed  CAS  Google Scholar 

  46. Asai M, Kawashima D, Katagiri K, Takeuchi R, Tohnai G, Ohtsuka K. Protective effect of a molecular chaperone inducer, paeoniflorin, on the HCl- and ethanol-triggered gastric mucosal injury. Life Sci. 2010;88:350–7.

    Article  PubMed  Google Scholar 

  47. Fu J, Li Y, Wang L, Gao B, Zhang N, Ji Q. Paeoniflorin prevents diabetic nephropathy in rats. Comp Med. 2009;59:557–66.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, and partially supported by Innovative Training Plan for Undergraduate Students of China Pharmaceutical University.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yue Dai.

Additional information

Responsible Editor: Michael Parnham.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, H., Bian, D., Jiao, X. et al. Paeoniflorin protects against lipopolysaccharide-induced acute lung injury in mice by alleviating inflammatory cell infiltration and microvascular permeability. Inflamm. Res. 60, 981–990 (2011). https://doi.org/10.1007/s00011-011-0359-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-011-0359-9

Keywords

Navigation