Abstract
The development of therapeutic alternatives to treat leishmaniasis has received considerable attention. The present study aimed to investigate the efficacy of the Agaricus blazei Murill water extract (AbM) to treat BALB/c mice infected with Leishmania amazonensis. First, a dose–titration curve was performed. The most well-defined concentration able to induce the most effective results in the infected animals, considering a daily administration of the product, was that of 100 mg kg−1 day−1. In this context, the AbM was administered orally, beginning on day 0 up to 20 days postinfection. Additional animals were treated with amphotericin B (AmpB, 5 mg kg−1 day−1) by peritoneal route for the same period of time, while the control group received distilled water. The animals were evaluated at 14 weeks post-infection, at which time the parasitological and immunological parameters were analyzed. Mice treated with the AbM presented a 60 % reduction in the inflammation of infected footpads as compared to untreated control-infected mice. Moreover, in the treated mice, as compared to the untreated controls, approximately 60 and 66 % reductions could be observed in the parasite burdens of the footpad and draining lymph nodes, respectively. In addition, no parasites could be detected in the spleen of treated mice at week 14 postinfection. These treated animals produced significantly higher levels of interferon gamma (IFN-γ) and nitric oxide (NO), higher levels of parasite-specific IgG2a isotype antibodies, and lower levels of interleukin (IL)-4, and IL-10 in the spleen and lymph node cell cultures than did the controls. Differences could be observed by comparing animals treated with AbM to those treated with AmpB, as indicated by a significant reduction in tissue parasitism, higher levels of IFN-γ and NO, and lower levels of IL-4 and IL-10, as well as by a decreased hepatic toxicity. In conclusion, the present study’s data show that the A. blazei Murill water extract presents a high potential for the treatment of leishmaniasis, although additional studies on mice, as well as on other mammal hosts, are warranted in an attempt to determine this extract’s true efficacy as compared to other known therapeutic products.
Similar content being viewed by others
References
Afonso LC, Scott P (1993) Immune responses associated with susceptibility of C57BL/10 mice to Leishmania amazonensis. Infect Immun 61:2952–2959
Aguiar MG, Silva DL, Nunan FA, Nunan EA, Fernandes AP, Ferreira LAM (2009) Combined topical paromomycin and oral miltefosine treatment of mice experimentally infected with Leishmania (Leishmania) major leads to reduction in both lesion size and systemic parasite burdens. J Antimicrob Chemother 64:1234–1240
Aguiar MG, Pereira AMM, Fernandes AP, Ferreira LAM (2010) Reductions in skin and systemic parasite burdens as a combined effect of topical paromomycin and oral miltefosine treatment of mice experimentally infected with Leishmania (Leishmania) amazonensis. Antimicrob Agents Chemother 54:4699–4704
Balaraman S, Tewary P, Singh VK, Madhubala R (2004) Leishmania donovani induces interferon regulatory factor in murine macrophages: a host defense response. Biochem Biophys Res Commun 317:639–647
Barral A, Pedral-Sampaio D, Grimaldi G Jr, Momen H, McMahon-Pratt D, Ribeiro-de-Jesus A, Almeida R, Badaró R, Barral-Netto M, Carvalho EM, Johnson WD Jr (1991) Leishmaniasis in Bahia, Brazil: evidence that Leishmania amazonensis produces a wide spectrum of clinical disease. AmJTrop Med Hyg 44:536–546
Berman J (2003) Current treatment approaches to leishmaniasis. Curr Opin Infect Dis 16:397–401
Berman F (2005) Clinical status of agents being developed for leishmaniasis. Expert Opin Invest Drugs 14:1337–1346
Bernardshaw S, Hetland G, Ellertsen LK, Tryggestad AM, Johnson E (2005) An extract of the medicinal mushroom Agaricus blazei Murill differentially stimulates production of pro-inflammatory cytokines in human monocytes and human vein endothelial cells in vitro. Inflammation 29:147–153
Bernardshaw S, Hetland G, Ellertsen LK, Tryggestad AMA, Johnson E (2006) An extract of the medicinal mushroom Agaricus blazei Murill differentially stimulates production of pro-inflammatory cytokines in human monocytes and human vein endothelial cells in vitro. Inflammation 29:147–153
Bernardshaw S, Lyberg T, Hetland G, Johnson E (2007) Effect of an extract of the mushroom Agaricus blazei Murill on expression of adhesion molecules and production of reactive oxygen species in monocytes and granulocytes in human whole blood ex vivo. APMIS 115:719–725
Coelho EAF, Tavares CAP, Carvalho FAA, Chaves KF, Teixeira KN, Rodrigues RC, Matlashewski G, Gazzinelli RT, Fernandes AP (2003) Immune responses induced by the Leishmania (Leishmania) donovani A2 antigen, but not by the LACK antigen, are protective against experimental Leishmania (Leishmania) amazonensis infection. Infect Immun 71:3988–3994
Croft SL, Coombs GH (2003) Leishmaniasis—current chemotherapy and recent advances in the search for novel drugs. Trends Parasitol 19:502–508
Croft SL, Olliaro P (2011) Leishmaniasis chemotherapy-challenges and opportunities. Clin Microbiol Infect 17:1478–1483
Cupolilo SM, Souza CS, Abreu-Silva AL, Calabrese KS, Goncalves da Costa SC (2003) Biological behavior of Leishmania (L.) amazonensis isolated from a human diffuse cutaneous leishmaniasis in inbred strains of mice. Histol Histopathol 18:1059–1065
Forland DT, Johnson E, Tryggestad AM, Lyberg T, Hetland G (2010) An extract based on the medicinal mushroom Agaricus blazei Murill stimulates monocyte-derived dendritic cells to cytokine and chemokine production in vitro. Cytokine 49:245–250
Frézard F, Demicheli C (2009) New delivery strategies for the old pentavalent antimonial drugs. Expert Opin Drug Deliv 7:1343–1358
Grimaldi G Jr, Tesh RB (1993) Leishmaniases of the New World: current concepts and implications for future research. Clin Microbiol Rev 6:230–250
Hsu CH, Hwang KC, Chiang YH, Chou P (2008) The mushroom Agaricus blazei Murill extract normalizes liver function in patients with chronic hepatitis B. J Altern Complement Med 14:299–301
Kedzierski L, Sakthianandeswaren A, Curtis JM, Andrews PC, Junk PC, Kedzierska K (2009) Leishmaniasis: current treatment and prospects for new drugs and vaccines. Curr Med Chem 16:599–614
Kim YW, Kim KH, Choi HJ, Lee DS (2005) Anti-diabetic activity of beta-glucans and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei. Biotechnol Lett 27:483–487
Kim CF, Jiang JJ, Leung KN, Fung KP, Lau CB (2009) Inhibitory effects of Agaricus blazei Murill extracts on human myeloid leukemia cells. J Ethnopharmacol 122:320–326
Mondal S, Bhattacharya P, Rahaman M, Ali N, Goswami RP (2010) A curative immune profile one week after treatment of Indian kala-azar patients predicts success with a short-course liposomal amphotericin B therapy. PLoS Negl Trop Dis 27:e764
Oliveira LF, Schubach AO, Martins MM, Passos SL, Oliveira RV, Marzochi MC, Andrade CA (2011) Systematic review of the adverse effects of cutaneous leishmaniasis treatment in the New World. Acta Trop 118:87–96
Padigel UM, Alexander J, Farrell JP (2003) The role of interleukin-10 in susceptibility of BALB/c mice to infection with Leishmania mexicana and Leishmania amazonensis. J Immunol 171:3705–3710
Sorimachi K, Akimoto K, Ikehara Y, Inafuku K, Okubo A, Yamazaki S (2001) Secretion TNF-α, IL-12 and nitric oxide by macrophages activated with Agaricus blazei Murill fractions in vitro. Cell Struct Funct 26:103–108
Talcott JA, Clark JA, Lee IP (2007) Measuring perceived effects of drinking an extract of basidiomycetes Agaricus blazei Murill: a survey of Japanese consumers with cancer. BMC Complement Alternat Med 29:7–32
Tang NY, Yang JS, Lin JP, Hsia TC, Fan MJ, Lin JJ, Weng SW, Ma YS, Lu HF, Shen JJ, Lin JG, Chung JG (2009) Effects of Agaricus blazei Murill extract on immune responses in normal BALB/c mice. In Vivo 23:761–766
Valadares DG, Duarte MC, Oliveira JS, Chávez-Fumagalli MA, Martins VT, Costa LE, Leite JPV, Santoro MM, Régis WCB, Tavares CAP, Coelho EAF (2011) Leishmanicidal activity of the Agaricus blazei Murill in different Leishmania species. Parasitol Int 60:357–363
Van Assche T, Deschacht M, Da Luz RA, Maes L, Cos P (2011) Leishmania-macrophage interactions: insights into the redox biology. Free Radic Biol Med 51:337–351
Vieira LQ, Goldschmidt M, Nashleanas M, Pfeffer K, Mak T, Scott P (1996) Mice lacking the TNF receptor p55 fail to resolve lesions caused by infection with Leishmania major, but control parasite replication. J Immunol 157:827–835
World Health Organization (2000) The disease and its impact. http://who.int/emc/diseases/leish/index.html
Wu MF, Hsu YM, Tang MC, Chen HC, Chung JG, Lu HF, Lin JP, Tang NY, Yeh C, Yeh MY (2011) Agaricus blazei Murill extract abrogates CCl4-induced liver injury in rats. In Vivo 25:35–40
Acknowledgments
This work was supported by grants from Pró-Reitoria de Pesquisa from UFMG (Edital 08/2011), FAPEMIG (CBB-APQ-00496-11, CBB-APQ-02364-08, and CBB-APQ-00496-11), CNPq (APQ-472090/2011-9), Instituto Nacional de Ciência e Tecnologia em Nanobiofarmacêutica (INCT NANO-BIOFAR), and Instituto Nacional de Ciência e Tecnologia em Vacinas (INCT-V), CNPq. DGV, APF, and EAFC are grant recipient of CNPq, while MACF is a grant recipient of CAPES. This study was in part supported in Spain by grants from Ministerio de Ciencia e Innovación FIS/PI1100095.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Valadares, D.G., Duarte, M.C., Ramírez, L. et al. Therapeutic efficacy induced by the oral administration of Agaricus blazei Murill against Leishmania amazonensis . Parasitol Res 111, 1807–1816 (2012). https://doi.org/10.1007/s00436-012-3028-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00436-012-3028-1