Therapeutic efficacy induced by the oral administration of Agaricus blazei Murill against Leishmania amazonensis
- 321 Downloads
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.
KeywordsNitric Oxide Infected Animal Visceral Leishmaniasis Leishmaniasis Cutaneous Leishmaniasis
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.
- 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 64:1234–1240PubMedCrossRefGoogle Scholar
- 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 54:4699–4704PubMedCrossRefGoogle Scholar
- 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 44:536–546Google Scholar
- 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 29:147–153PubMedCrossRefGoogle Scholar
- 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 29:147–153CrossRefGoogle Scholar
- 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 71:3988–3994PubMedCrossRefGoogle Scholar
- 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 29:7–32Google Scholar
- World Health Organization (2000) The disease and its impact. http://who.int/emc/diseases/leish/index.html