Skip to main content

Advertisement

SpringerLink
Log in

Therapeutic potential of biodegradable microparticles containing Punica granatum L. (pomegranate) in murine model of asthma

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

Abstract

Objective and design

Among the options for treatment of diseases affecting the respiratory system, especially asthma, drug delivering systems for intranasal application represent an important therapeutic approach at the site of inflammation. The present study aimed to evaluate the therapeutic effect of biodegradable microparticles formed by poly lactic-co-glycolic acid (PLGA) containing encapsulated pomegranate extract on a murine model of asthma.

Material

The extract was acquired from the leaves of P. granatum and characterized qualitatively by HPLC. A w/o/w emulsion solvent extraction–evaporation method was chosen to prepare the microparticles containing pomegranate encapsulated extract (MP).

Treatment

OVA-sensitized BALB/c mice were used as asthma model and treated with dexamethasone and P. granatum extract in solution form or encapsulated into microparticles.

Results

MP were able to inhibit leukocytes’ recruitment to bronchoalveolar fluid, especially, eosinophils, decreasing cytokines (IL-1β and IL-5) and protein levels in the lungs.

Conclusions

This approach can be used as an alternative/supplementary therapy based on the biological effects of P. granatum for managing inflammatory processes, especially those with pulmonary complications.

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.

Institutional subscriptions

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

Similar content being viewed by others

References

  1. Barnes PJ. Pathophysiology of asthma. Eur Respir Mon. 2003;8:84–113.

    Google Scholar 

  2. Tattersfield AE, Knox AJ, Britton JR, Hall IP. Asthma. Lancet. 2002;360:1313–22.

    Article  PubMed  CAS  Google Scholar 

  3. Barnes PJ. New drugs for asthma. Nat Rev Drug Discov. 2004;3:831–44.

    Article  PubMed  CAS  Google Scholar 

  4. Yang EJ, Lee JS, Yun CY, Kim JH, Kim JS, Kim DH, Kim IS. Inhibitory effects of Duchesnea chrysantha extract on ovalbumin-induced lung inflammation in a mouse model of asthma. J Ethnopharmacol. 2008;118:102–7.

    Article  PubMed  Google Scholar 

  5. Yuk JE, Woo JS, Yun CY, Lee JS, Kim JH, Song GY, Yang EJ, Hur IK, Kim IS. Effects of lactose-β-sitosterol and β-sitosterol on ovalbumin-induced lung inflammation in actively sensitized mice. Int Immunopharmacol. 2007;7:1517–27.

    Article  PubMed  CAS  Google Scholar 

  6. Clardy J, Walsh C. Lessons from natural molecules. Nature. 2004;432:829–37.

    Article  PubMed  CAS  Google Scholar 

  7. Verpoorte R. Exploration of nature’s chemodiversity: the role of secondary metabolites as leads in drug development. Drug Discov Today. 1999;3:232–8.

    Article  Google Scholar 

  8. Koehn FE, Carter GT. The evolving role of natural products in drug discovery. Nat Rev Drug Discov. 2005;4:206–20.

    Article  PubMed  CAS  Google Scholar 

  9. Rogerio AP, Fontanari C, Borducchi E, Keller AC, Russo M, Soares EG, Albuquerque DA, Faccioli LH. Anti-inflammatory effects of Lafoensia pacari and ellagic acid in a murine model of asthma. Eur J Pharmacol. 2008;580:262–70.

    Article  PubMed  CAS  Google Scholar 

  10. Rogerio AP. SÁ-NUNES A, Faccioli LH. The activity of medicinal plants and secondary metabolites on eosinophilic inflammation. Pharmacol Res. 2010;62:298–307.

    Article  PubMed  CAS  Google Scholar 

  11. Jurenka JS. Therapeutic applications of pomegranate (Punica granatum L.): a review. Altern Med Rev. 2008;13:128–44.

    PubMed  Google Scholar 

  12. Fischer UA, Carle R, Kammerer DR. Identification and quantification of phenolic compounds from pomegranate (Punica granatum L.) peel, mesocarp, aril and differently produced juices by HPLC-DAD–ESI/MSn. Food Chem. 2011;127:807–21.

    Article  PubMed  CAS  Google Scholar 

  13. Lansky EP, Newman RA. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol. 2007;109:177–206.

    Article  PubMed  CAS  Google Scholar 

  14. Lansky E, Shubert S, Newman I. Pharmacological and therapeutic properties of pomegranate. CIHEAM–Options Mediterraneennes. 2004; 231–235.

  15. Lee SI, Kim BS, Kim KS, Lee S, Shin KS, Lim JS. Immune-suppressive activity of punicalagin via inhibition of NFAT activation. Biochem Biophys Res Commun. 2008;371:799–803.

    Article  PubMed  CAS  Google Scholar 

  16. Romier B, Van De Walle J, During A, Larondelle Y, Schneider YJ. Modulation of signalling nuclear factor-kappaB activation pathway by polyphenols in human intestinal Caco-2 cells. Br J Nutr. 2008;100:542–51.

    Article  PubMed  CAS  Google Scholar 

  17. Nicolete R, Lima KM, Rodrigues Júnior JM, Baruffi MD, Medeiros AI, Bentley MVLB, Silva CL, Faccioli LH. In vitro and in vivo activities of leukotrienes B4-loaded biodegradable microspheres. Prostaglandins Other Lipid Mediators. 2007;83:121–9.

    Article  PubMed  CAS  Google Scholar 

  18. Nicolete R, Rius C, Piqueras L, Jose PJ, Sorgi CA, Soares EG, Sanz MJ, Faccioli LH. Leukotriene B4-loaded microspheres: a new therapeutic strategy to modulate cell activation. BMC Immunol. 2008;9:1–11.

    Article  Google Scholar 

  19. Oh YJ, Lee J, Seo JY, Rhim T, Kim S, Yoon HJ, Lee KY. Preparation of budesonide-loaded porous PLGA microparticles and their therapeutic efficacy in a murine asthma model. J Controlled Release. 2011;150:56–62.

    Article  CAS  Google Scholar 

  20. Sung JC, Pulliam BL, Edwards DA. Nanoparticles for drug delivery to the lungs. Trends Biotechnol. 2007;25:563–70.

    Article  PubMed  CAS  Google Scholar 

  21. Pilcer G, Amighi K. Formulation strategy and use of excipients in pulmonary drug delivery. Int J Pharm. 2010;392:1–19.

    Article  PubMed  CAS  Google Scholar 

  22. Bekir J, Mars M, Souchard JP, Bouajila J. Assessment of antioxidant, anti-inflammatory, anti-cholinesterase and cytotoxic activities of pomegranate (Punica granatum) leaves. Food Chem Toxicol. 2013;55:470–5.

    Article  PubMed  CAS  Google Scholar 

  23. Gil MI, Tomás-Barberán FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant Activity of Pomegranate Juice and Its Relationship with Phenolic Composition and Processing. J Agric Food Chem. 2000;48:4581–9.

    Article  PubMed  CAS  Google Scholar 

  24. Ismail T, Sestili P, Akhtar S. Pomegranate peel and fruit extracts: a review of potential anti-inflammatory and anti-infective effects. J Ethnopharmacol. 2012;143:397–405.

    Article  PubMed  CAS  Google Scholar 

  25. Wager S, Lundblad LKA, Ekman M, Irvin CG, Bates JHT. The allergic mouse model of asthma: normal smooth muscle in an abnormal lung? J Appl Physiol. 2004;96:2019–27.

    Article  Google Scholar 

  26. Nicolete R, Secatto A, Pereira PAT, Soares EG, Faccioli LH. Leukotriene B4-loaded microspheres as a new approach to enhance antimicrobial responses in Histoplasma capsulatum-infected mice. Int J Antimicr Agets. 2009;4:365–9.

    Article  Google Scholar 

  27. Cook-Mills JM, Deem TL. Active participation of endothelial cells in inflammation. J Leukoc Biol. 2005;77:487–95.

    Article  PubMed  CAS  Google Scholar 

  28. Balwani S, Nandi D, Jaisankar P, Ghosh B. 2-Methyl-pyran-4-one-3-O-β-D-glucopyranoside isolated from leaves of Punica granatum inhibits the TNFα-induced cell adhesion molecules expression by blocking nuclear transcription factor-кB (NF-кB). Biochimie. 2011;93:921–30.

    Article  PubMed  CAS  Google Scholar 

  29. Nicolete R, Santos DF, Faccioli LH. The uptake of PLGA micro or nanoparticles by macrophages provokes distinct in vitro inflammatory response. Int Immunopharmacol. 2011;11:1557–63.

    Article  PubMed  CAS  Google Scholar 

  30. Whelan R, Kim C, Chen M, Leiter J, Grunstein MM, Hakonarson H. Role and regulation of interleukin-1 molecules in pro-asthmatic sensitised airway smooth muscle. Eur Respir J. 2004;24:559–67.

    Article  PubMed  CAS  Google Scholar 

  31. Faccioli LH, Mokwa VF, Silva CL, Rocha GM, Araujo JI, Nahori MA, Vargaftig BB. IL-5 drives eosinophils from bone marrow to blood and tissues in a guinea-pig model of visceral larva migrans syndrome. Mediators Inflamm. 1996;5:24–31.

    Article  PubMed  CAS  Google Scholar 

  32. Rogerio AP, Sá-Nunes A, Albuquerque DA, Anibal FF, Medeiros AI, Machado ER, Souza AO, Prado JC Jr, Faccioli LH. Lafoensia pacari extract inhibits IL-5 production in toxocariasis. Parasite Immunol. 2003;25:393–400.

    Article  PubMed  CAS  Google Scholar 

  33. Lampinen M, Carlson M, Hakansson LD, Venge P. Cytokine-regulated accumulation of eosinophils in inflammatory disease. Allergy. 2004;59:793–805.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão (FAPEMA) and Universidade Ceuma, São Luis, Maranhão. We would like to thank the technician Ana Cleia Pestana from the Universidade Ceuma for the assistance in the histological sections.

Author information

Authors and Affiliations

  1. Pró-Reitoria de Pós-Graduação, Pesquisa e Extensão, Universidade CEUMA (UNICEUMA), Rua Josué Montello, 1, São Luís, Maranhão, 65075-120, Brazil

    Jéssica F. F. de Oliveira, Marcos A. G. Grisotto & Roberto Nicolete

  2. Instituto Florence de Ensino, Rua Rio Branco, 216, São Luís, Maranhão, Brazil

    Diego V. Garreto

  3. Department of Pathology, Laboratory of Immunophysiology, Biological and Health Sciences Center, Federal University of Maranhão (UFMA), São Luís, Maranhão, 65085-580, Brazil

    Mayara C. P. da Silva, Thiare S. Fortes & Flávia R. F. Nascimento

  4. Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, Ribeirão Preto, São Paulo, 14040-903, Brazil

    Rejane B. de Oliveira & Fernando B. Da Costa

  5. Laboratório de Biotecnologia Aplicada à Saúde, Fundação Oswaldo Cruz—Fiocruz Rondônia, Rua da Beira 7671, Porto Velho, Rondônia, 76812-245, Brazil

    Roberto Nicolete

Authors
  1. Jéssica F. F. de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diego V. Garreto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mayara C. P. da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thiare S. Fortes
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rejane B. de Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Flávia R. F. Nascimento
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Fernando B. Da Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marcos A. G. Grisotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Roberto Nicolete
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roberto Nicolete.

Additional information

Responsible Editor: Ji Zhang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Oliveira, J.F.F., Garreto, D.V., da Silva, M.C.P. et al. Therapeutic potential of biodegradable microparticles containing Punica granatum L. (pomegranate) in murine model of asthma. Inflamm. Res. 62, 971–980 (2013). https://doi.org/10.1007/s00011-013-0659-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-013-0659-3

Keywords

Search

Navigation