Skip to main content

Advertisement

SpringerLink
Log in

Propolis reduces Leishmania amazonensis-induced inflammation in the liver of BALB/c mice

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

Abstract

Experimental models of mouse paw infection with L. amazonensis show an induction of a strong inflammatory response in the skin, and parasitic migration may occur to secondary organs with consequent tissue injury. There are few studies focusing on the resolution of damage in secondary organs caused by Leishmania species-related cutaneous leishmaniasis. We investigated the propolis treatment effect on liver inflammation induced by Leishmania amazonensis infection in the mouse paw. BALB/c mice were infected in the hind paw with L. amazonensis (107) promastigote forms. After 15 days, animals were treated daily with propolis (5 mg/kg), Glucantime (10 mg/kg), or with propolis plus Glucantime combined. After 60 days, mice were euthanized and livers were collected for inflammatory process analysis. Liver microscopic analysis showed that propolis reduced the inflammatory process compared to untreated infected control. There was a decrease of liver myeloperoxidase and N-acetyl-β-glucosaminidase activity levels, collagen fiber deposition, pro-inflammatory cytokine production, and plasma aspartate transaminase and alanine transaminase levels. Furthermore, propolis treatment enhanced anti-inflammatory cytokine levels and reversed hepatosplenomegaly. Our data demonstrated that daily low doses of Brazilian propolis reduced the secondary chronic inflammatory process in the liver caused by L. amazonensis subcutaneous infection in a susceptible mice strain.

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
Fig. 7

Similar content being viewed by others

References

  • Abreu-Silva AL, Calabrese KS, Cupolilo SMN, Cardoso FO, Souza CS, Gonçalves da Costa SC (2004) Histopathological studies of visceralized Leishmania (Leishmania) amazonensis in mice experimentally infected. Vet Parasitol 121:179–187. doi:10.1016/j.vetpar.2004.03.002

    Article  CAS  PubMed  Google Scholar 

  • Ayres DC, Marcucci MC, Giorgio S (2007) Effects of Brazilian propolis on Leishmania amazonensis. Mem Inst Oswaldo Cruz 102:215–220. doi:10.1590/S0074-02762007005000020

    Article  PubMed  Google Scholar 

  • Ayres DC, Fedele TA, Marcucci MC, Giorgio S (2011) Potential utility of hyperbaric oxygen therapy and propolis in enhancing the leishmanicidal activity of glucantime. Rev Inst Med Trop Sao Paulo 53:329–334. doi:10.1590/S0036-46652011000600006

    Article  PubMed  Google Scholar 

  • Baranwal AK, Mandal RN, Singh R (2007) Fulminant hepatic failure complicating visceral leishmaniasis in an apparently immunocompetent child. Indian J Pediatr 74:489–491. doi:10.1007/s12098-007-0083-1

    Article  PubMed  Google Scholar 

  • Barbosa MH, Zuffi FB, Maruxo HB, Jorge LLR (2009) Therapeutic properties of propolis for treatment of skin lesions. Acta Paul Enferm 22(3):318–322

    Article  Google Scholar 

  • Barral A, Badaró R, Barral-Netto M, Grimaldi G Jr, Momem H, Carvalho EM (1986) Isolation of Leishmania mexicana amazonensis from the bone marrow in a case of American visceral leishmaniasis. Am J Trop Med Hyg 35:732–734

    CAS  PubMed  Google Scholar 

  • Barral A, Pedral-Sampaio D, Grimaldi Júnior G, Momen H, McMahon-Pratt D, Ribeiro de Jesus A, Almeida R, Badaro R, Barral-Netto M, Carvalho EM, Warren Jr DJ (1991) Leishmaniasis in Bahia, Brazil: evidence that Leishmania amazonensis produces a wide spectrum of clinical disease. Am J Trop Med Hyg 44:536–546

    CAS  PubMed  Google Scholar 

  • Bataller R, Brenner DA (2005) Liver fibrosis. J Clin Invest 115:209–218. doi:10.1172/JCI24282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Batista LLV, Campesatto EA, de Assis MLB, Barbosa AP, Grillo LA, Dornelas CB (2012) Comparative study of topical green and red propolis in the repair of wounds induced in rats. Rev Col Bras Cir 39:515–520

    Article  PubMed  Google Scholar 

  • Bittencourt AL, Barral A (1991) Evaluation of the histopathological classifications of American cutaneous and mucocutaneous leishmaniasis. Mem Inst Oswaldo Cruz 86:51–56

    Article  CAS  PubMed  Google Scholar 

  • Búfalo MC, Ferreira I, Costa G, Francisco V, Liberal J, Cruz MT, Lopes MC, Batista MT, Sforcin JM (2013) Propolis and its constituent caffeic acid suppress LPS-stimulated pro-inflammatory response by blocking NF-κB and MAPK activation in macrophages. J Ethnopharmacol 149:84–92. doi:10.1016/j.jep.2013.06.004

    Article  PubMed  Google Scholar 

  • Da Silva SS, Thomé G d S, Cataneo AHD, Miranda MM, Felipe I, Andrade CG, Watanabe MA, Piana GM, Sforcin JM, Pavanelli WR, Conchon-Costa I (2013) Brazilian propolis antileishmanial and immunomodulatory effects. Evid Based Complement Alternat Med 2013:673058. doi:10.1155/2013/673058

    PubMed  PubMed Central  Google Scholar 

  • Desjeux P (2004) Leishmaniasis: current situation and new perspectives. Comp Immunol Microbiol Infect Dis 27:305–318. doi:10.1016/j.cimid.2004.03.004

    Article  CAS  PubMed  Google Scholar 

  • Dimov V, Ivanovska N, Bankova V, Popov S (1992) Immunomodulatory action of propolis: IV. Prophylactic activity against gram-negative infections and adjuvant effect of the water-soluble derivative. Vaccine 10:817–823

    Article  CAS  PubMed  Google Scholar 

  • Duarte MI, Corbett CE (1987) Histopathological patterns of the liver involvement in visceral leishmaniasis. Rev Inst Med Trop Sao Paulo 29:131–136

    Article  CAS  PubMed  Google Scholar 

  • Duran G, Duran N, Culha G, Culha G, Ozcan B, Oztas H, Ozer B (2008) In vitro antileishmanial activity of Adana propolis samples on Leishmania tropica: a preliminary study. Parasitol Res 102:1217–1225. doi:10.1007/s00436-008-0896-5

    Article  CAS  PubMed  Google Scholar 

  • Engwerda CR, Kaye PM (2000) Organ-specific immune responses associated with infectious disease. Immunol Today 21:73–78

    Article  CAS  PubMed  Google Scholar 

  • Ferreira FM, Castro RAO, Batista MA, Rossi FMO, Silveira-Lemos D, Frézard F, Moura SAL, Rezende SA (2014) Association of water extract of green propolis and liposomal meglumine antimoniate in the treatment of experimental visceral leishmaniasis. Parasitol Res 113:533–543. doi:10.1007/s00436-013-3685-8

    Article  PubMed  Google Scholar 

  • Fichtner-Feigl S, Strober W, Kawakami K, Puri RK, Kitani A (2006) IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis. Nat Med 12:99–106. doi:10.1038/nm1332

    Article  CAS  PubMed  Google Scholar 

  • Frenkel K, Wei H, Bhimani R, Ye J, Zadunaisky JA, Huang MT, Ferraro T, Conney AH, Grunberger D (1993) Inhibition of tumor promoter-mediated processes in mouse skin and bovine lens by caffeic acid phenethyl ester. Cancer Res 53:1255–1261

    CAS  PubMed  Google Scholar 

  • Friedman SL (2008) Mechanisms of hepatic fibrogenesis. Gastroenterology 134:1655–1669. doi:10.1053/j.gastro.2008.03.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • George J (2003) Ascorbic acid concentrations in dimethylnitrosamine-induced hepatic fibrosis in rats. Clin Chim Acta 335:39–47

    Article  CAS  PubMed  Google Scholar 

  • George J, Chandrakasan G (1996) Glycoprotein metabolism in dimethylnitrosamine induced hepatic fibrosis in rats. Int J Biochem Cell Biol 28:353–361

    Article  CAS  PubMed  Google Scholar 

  • George J, Tsutsumi M, Takase S (2004) Expression of hyaluronic acid in N-nitrosodimethylamine induced hepatic fibrosis in rats. Int J Biochem Cell Biol 36:307–319

    Article  CAS  PubMed  Google Scholar 

  • Grevelink SA, Lerner EA (1996) Leishmaniasis. J Am Acad Dermatol 34:257–272

    Article  CAS  PubMed  Google Scholar 

  • Gupta G, Oghumu S, Satoskar AR (2013) Mechanisms of immune evasion in leishmaniasis. Adv Appl Microbiol 82:155–184. doi:10.1016/B978-0-12-407679-2.00005-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gutierrez Y, Maksem JA, Reiner NE (1984) Pathologic changes in murine leishmaniasis (Leishmania donovani) with special reference to the dynamics of granuloma formation in the liver. Am J Pathol 114:222–230

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hohmann MSN, Cardoso RDR, Pinho-Ribeiro FA, Crespigio J, Cunha TM, Alves-Filho JC, da Silva RV, Pinge-Filho P, Ferreira SH, Cunha FQ, Casagrande R, Verri Jr WA (2013) 5-lipoxygenase deficiency reduces acetaminophen-induced hepatotoxicity and lethality. Biomed Res Int 2013:627046. doi:10.1155/2013/627046

    Article  PubMed  PubMed Central  Google Scholar 

  • Ikeda R, Yanagisawa M, Takahashi N, Kawada T, Kumazawa S, Yamaotsu N, Nakagome I, Hirono S, Tsuda T (2011) Brazilian propolis-derived components inhibit TNF-α-mediated downregulation of adiponectin expression via different mechanisms in 3T3-L1 adipocytes. Biochim Biophys Acta 1810:695–703. doi:10.1016/j.bbagen.2011.04.007

    Article  CAS  PubMed  Google Scholar 

  • Ji J, Sun J, Soong L (2003) Impaired expression of inflammatory cytokines and chemokines at early stages of infection with Leishmania amazonensis. Infect Immun 71:4278–4288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones DE, Buxbaum LU, Scott P (2000) IL-4-independent inhibition of IL-12 responsiveness during Leishmania amazonensis infection. J Immunol 165:364–372

    Article  CAS  PubMed  Google Scholar 

  • Khorasgani EM, Karimi AH, Nazem MR (2010) A comparison of healing effects of Propolis and silver sulfadiazine on full thickness skin wounds in rats. In: Pak Vet J 30(2).

  • Leite VH, Croft SL (1996) Hepatic extracellular matrix in BALB/c mice infected with Leishmania donovani. Int J Exp Pathol 77:181–190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Machado GM de C, Leon LL, De Castro SL (2007) Activity of Brazilian and Bulgarian propolis against different species of Leishmania. Mem Inst Oswaldo Cruz 102:73–77

  • Magill AJ, Grögl M, Gasser RA, Sun W, Oster CN (1993) Visceral infection caused by leishmania tropica in veterans of operation desert storm. N Engl J Med 328:1383–1387. doi:10.1056/NEJM199305133281904

    Article  CAS  PubMed  Google Scholar 

  • Miranda MM, Panis C, Cataneo AHD, da Silva SS, Kawakami NY, Lopes LGF, Morey AT, Yamauchi LM, Andrade CGTJ, Cecchini R, Silva JJN, Sforcin JM, Conchon-Costa I, Pavanelli WR (2015) Nitric oxide and Brazilian propolis combined accelerates tissue repair by modulating cell migration, cytokine production and collagen deposition in experimental leishmaniasis. PLoS ONE 10(5):e0125101. doi:10.1371/journal.pone.0125101

    Article  PubMed  PubMed Central  Google Scholar 

  • Missima F, Sforcin JM (2008) Green Brazilian propolis action on macrophages and lymphoid organs of chronically stressed mice. Evid Based Complement Alternat Med 5:71–75. doi:10.1093/ecam/nel112

    Article  PubMed  PubMed Central  Google Scholar 

  • Miyataka H, Nishiki M, Matsumoto H, Fujimoto T, Matsuka M, Satoh T (1997) Evaluation of propolis. I. Evaluation of Brazilian and Chinese propolis by enzymatic and physico-chemical methods. Biol Pharm Bull 20:496–501

    Article  CAS  PubMed  Google Scholar 

  • Mohareb EW, Mikhail EM, Youssef FG (1996) Leishmania tropica in Egypt: an undesirable import. Trop Med Int Health 1:251–254

    Article  CAS  PubMed  Google Scholar 

  • Montes GS, Junqueira LC (1991) The use of the Picrosirius-polarization method for the study of the biopathology of collagen. Mem Inst Oswaldo Cruz 86(Suppl 3):1–11

    Article  PubMed  Google Scholar 

  • Murad JM, Calvi SA, Soares AM, Bankova V, Sforcin JM (2002) Effects of propolis from Brazil and Bulgaria on fungicidal activity of macrophages against Paracoccidioides brasiliensis. J Ethnopharmacol 79:331–334

    Article  CAS  PubMed  Google Scholar 

  • Murray HW (2001) Tissue granuloma structure-function in experimental visceral leishmaniasis. Int J Exp Pathol 82:249–267

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nieto N (2006) Oxidative-stress and IL-6 mediate the fibrogenic effects of [corrected] Kupffer cells on stellate cells. Hepatology 44:1487–1501. doi:10.1002/hep.21427

    Article  CAS  PubMed  Google Scholar 

  • Nylén S, Gautam S (2010) Immunological perspectives of leishmaniasis. J Glob Infect Dis 2:135–146. doi:10.4103/0974-777X.62876

    Article  PubMed  PubMed Central  Google Scholar 

  • Okamoto Y, Tanaka M, Fukui T, Masuzawa T (2012) Brazilian propolis inhibits the differentiation of Th17 cells by inhibition of interleukin-6-induced phosphorylation of signal transducer and activator of transcription 3. Immunopharmacol Immunotoxicol 34:803–809. doi:10.3109/08923973.2012.657304

    Article  CAS  PubMed  Google Scholar 

  • Olczyk P, Ramos P, Komosinska-Vassev K, Stojko J, Pilawa B (2013a) Positive effect of propolis on free radicals in burn wounds. Evid Based Complement Alternat Med 2013:356737. doi:10.1155/2013/356737

    PubMed  PubMed Central  Google Scholar 

  • Olczyk P, Wisowski G, Komosinska-Vassev K, Stojko J, Klimek K, Olczyk M, Kozma EM (2013b) Propolis modifies collagen types I and III accumulation in the matrix of burnt tissue. Evid Based Complement Alternat Med 2013:423809. doi:10.1155/2013/423809

    PubMed  PubMed Central  Google Scholar 

  • Orsi RO, Funari SRC, Soares AMVC, Calvi SA, Oliveira SL, Sforcin JM, Bankova V (2000) Immunomodulatory action of propolis on macrophage activation. J Venom Anim Toxins 6:205–219. doi:10.1590/S0104-79302000000200006

    Article  Google Scholar 

  • Orsi RO, Fernandes A, Bankova V, Sforcin JM (2012) The effects of Brazilian and Bulgarian propolis in vitro against salmonella typhi and their synergism with antibiotics acting on the ribosome. Nat Prod Res 26:430–437. doi:10.1080/14786419.2010.498776

    Article  CAS  PubMed  Google Scholar 

  • Ozbilge H, Kaya EG, Albayrak S, Silici S (2010) Anti-leishmanial activities of ethanolic extract of Kayseri propolis. In: African J Microbiol Res 4(7).

  • Pontin K, Da Silva Filho A a, Santos FF, Silva ML, Cunha WR, Nanayakkara NP, Bastos JK, de Albuquerque S (2008) In vitro and in vivo antileishmanial activities of a Brazilian green propolis extract. Parasitol Res 103:487–492. doi:10.1007/s00436-008-0970-z

    Article  PubMed  Google Scholar 

  • Ramos AFN, Miranda JL (2007) Propolis: a review of its anti-inflammatory and healing actions. J Venom Anim Toxins incl Trop Dis 13:697–710

    Article  CAS  Google Scholar 

  • Reithinger R, Dujardin J-C, Louzir H, Pirmez C, Alexander B, Brooker S (2007) Cutaneous leishmaniasis. Lancet Infect Dis 7:581–596. doi:10.1016/S1473-3099(07)70209-8

    Article  PubMed  Google Scholar 

  • Ribeiro-Romão RP, Moreira OC, Osorio EY, Cysne-Finkelstein L, Gomes-Silva A, Valverde JG, Pirmez C, Da-Cruz AM, Pinto EF (2014) Comparative evaluation of lesion development, tissue damage, and cytokine expression in golden hamsters (Mesocricetus auratus) infected by Inocula with different Leishmania (Viannia) braziliensis concentrations. Infect Immun 82:5203–5213. doi:10.1128/IAI.02083-14

    Article  PubMed  PubMed Central  Google Scholar 

  • Roberts M, Alexander J, Blackwell JM (1989) Influence of Lsh, H-2, and an H-11-linked gene on visceralization and metastasis associated with Leishmania mexicana infection in mice. Infect Immun 57:875–881

    CAS  PubMed  PubMed Central  Google Scholar 

  • Seo KW, Park M, Song YJ, Kim SJ, Yoon KR (2003) The protective effects of Propolis on hepatic injury and its mechanism. Phytother Res 17:250–253. doi:10.1002/ptr.1120

    Article  PubMed  Google Scholar 

  • Sforcin JM (2007) Propolis and the immune system: a review. J Ethnopharmacol 113:1–14. doi:10.1016/j.jep.2007.05.012

    Article  CAS  PubMed  Google Scholar 

  • Soliman MFM (2006) The persistence, dissemination, and visceralization tendency of Leishmania major in Syrian hamsters. Acta Trop 97:146–150. doi:10.1016/j.actatropica.2005.09.007

    Article  CAS  PubMed  Google Scholar 

  • Sundar S, Chakravarty J (2013) Leishmaniasis: an update of current pharmacotherapy. Expert Opin Pharmacother 14:53–63. doi:10.1517/14656566.2013.755515

    Article  CAS  PubMed  Google Scholar 

  • Volpert R, Elstner EF (1996) Interactions of different extracts of propolis with leukocytes and leukocytic enzymes. Arzneimittelforschung 46:47–51

    CAS  PubMed  Google Scholar 

  • Walton BC, Intermill RW, Hajduk ME (1977) Differences in biological characteristics of three Leishmania isolates from patients with espundia. Am J Trop Med Hyg 26:850–855

    CAS  PubMed  Google Scholar 

  • Wilson ME, Jeronimo SMB, Pearson RD (2005) Immunopathogenesis of infection with the visceralizing Leishmania species. Microb Pathog 38:147–160. doi:10.1016/j.micpath.2004.11.002

    Article  CAS  PubMed  Google Scholar 

  • Wynn TA (2004) Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol 4:583–594. doi:10.1038/nri1412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeisberg M, Kramer K, Sindhi N, Sarkar P, Upton M, Kalluri R (2006) De-differentiation of primary human hepatocytes depends on the composition of specialized liver basement membrane. Mol Cell Biochem 283:181–189. doi:10.1007/s11010-006-2677-8

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Dr. A. Leyva helped with English editing of the manuscript.

This work was supported by Brazilian grants from Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Secretaria da Ciência, Tecnologia e Ensino Superior (SETI)/Fundação Araucária, and Governo do Estado do Paraná.

Author information

Authors and Affiliations

  1. Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, 86057-970, Paraná, Brazil

    Suelen S. da Silva, Sandra S. Mizokami, Jacqueline R. Fanti, Milena M. Miranda, Natalia Y. Kawakami, Maria A. E. Watanabe, Wander R. Pavanelli, Waldiceu A. Verri Jr, Ionice Felipe & Ivete Conchon-Costa

  2. Departamento de Histologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, 86057-970, Paraná, Brazil

    Fernanda Humel Teixeira & Eduardo J. A. Araújo

  3. Laboratório de Mediadores Inflamatórios, Universidade do Oeste do Paraná, UNIOESTE, Francisco Beltrão, 85605-010, Paraná, Brazil

    Carolina Panis

  4. Departamento de Microbiologia e Imunologia, Instituto de Biociências, Universidade Estadual Paulista, UNESP, Botucatu, 18618-970, São Paulo, Brazil

    José M. Sforcin

Authors
  1. Suelen S. da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandra S. Mizokami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jacqueline R. Fanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Milena M. Miranda
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Natalia Y. Kawakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fernanda Humel Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Eduardo J. A. Araújo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Carolina Panis
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Maria A. E. Watanabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. José M. Sforcin
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Wander R. Pavanelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Waldiceu A. Verri Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Ionice Felipe
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ivete Conchon-Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Suelen S. da Silva.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

da Silva, S.S., Mizokami, S.S., Fanti, J.R. et al. Propolis reduces Leishmania amazonensis-induced inflammation in the liver of BALB/c mice. Parasitol Res 115, 1557–1566 (2016). https://doi.org/10.1007/s00436-015-4890-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00436-015-4890-4

Keywords

Search

Navigation