Leishmanicidal activity of Himatanthus sucuuba latex against Leishmania amazonensis.
ABSTRACT Himatanthus sucuuba (HsL) latex exhibited a potent leishmanicidal activity against intracellular amastigotes of Leishmania amazonensis, a causative agent of cutaneous leishmaniasis. HsL inhibited intracellular amastigote growth in a dose-dependent manner (IC(50)=15.7microg/mL). Moreover, HsL increased nitric oxide (NO) and Tumor Nuclear Factor-alpha (TNF-alpha) and decreased Transforming Growth Factor-beta (TGF-beta) production in macrophages. As assessed by plasma membrane integrity and mitochondrial activity, HsL showed low toxicity for host macrophages. HsL in vivo was active by the oral route, reducing the parasite load in established footpad lesions after only five doses. In summary, these findings support HsL as an interesting candidate for further evaluations regarding its potential application as a therapeutical agent against Leishmania.
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Article: Advances in leishmaniasis.[show abstract] [hide abstract]
ABSTRACT: Governed by parasite and host factors and immunoinflammatory responses, the clinical spectrum of leishmaniasis encompasses subclinical (inapparent), localised (skin lesions), and disseminated infection (cutaneous, mucosal, or visceral). Symptomatic disease is subacute or chronic and diverse in presentation and outcome. Clinical characteristics vary further by endemic region. Despite T-cell-dependent immune responses, which produce asymptomatic and self-healing infection, or appropriate treatment, intracellular infection is probably life-long since targeted cells (tissue macrophages) allow residual parasites to persist. There is an epidemic of cutaneous leishmaniasis in Afghanistan and Pakistan and of visceral infection in India and Sudan. Diagnosis relies on visualising parasites in tissue or serology; culture and detection of parasite DNA are useful in the laboratory. Pentavalent antimony is the conventional treatment; however, resistance of visceral infection in India has spawned new treatment approaches--amphotericin B and its lipid formulations, injectable paromomycin, and oral miltefosine. Despite tangible advances in diagnosis, treatment, and basic scientific research, leishmaniasis is embedded in poverty and neglected. Current obstacles to realistic prevention and proper management include inadequate vector (sandfly) control, no vaccine, and insufficient access to or impetus for developing affordable new drugs.The Lancet 01/2005; 366(9496):1561-77. · 39.06 Impact Factor
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ABSTRACT: The aim of this study was to characterize the in vitro antileishmanial activity of quassin, a traditional Chinese herbal medicine. The cytotoxic effect of quassin was studied in murine peritoneal macrophages at various concentrations using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide method. The role of quassin as an antileishmanial agent was evaluated by microscopic counting of intracellular amastigotes in macrophages stained with Giemsa. To understand the effector mechanism of quassin-treated macrophages against leishmanial parasites, western blot and real-time PCR analysis of inducible nitric oxide (NO) synthase 2 (iNOS2) were done followed by measurement of NO generation by Griess reaction. The effect of quassin on the production of Th1 cytokines such as interleukin (IL)-12 and tumour necrosis factor (TNF)-alpha and Th2 cytokines such as IL-10 and transforming growth factor-beta was measured by ELISA, and the mRNA expression of these cytokines was analysed by real-time PCR. Quassin at a dose of 25 microg/mL (64.36 microM) showed less cytotoxicity to the host murine peritoneal macrophages but at the same dose was effective enough to control the intracellular parasitic load compared with higher doses of quassin. Leishmania donovani is known to exert its pathogenic effects mainly by the suppression of NO generation and subversion of the cellular inflammatory responses in the macrophages. Quassin was found to induce a potent host-protective immune response by enhancing NO generation and iNOS2 expression both at a protein and mRNA level and by up-regulating pro-inflammatory cytokines such as TNF-alpha and IL-12 in L. donovani-infected macrophages with concurrent inhibition of anti-inflammatory responses. These findings strongly support the effectiveness of quassin as a potent immunomodulatory tool for controlling the establishment of leishmanial parasite within the host macrophages.Journal of Antimicrobial Chemotherapy 12/2008; 63(2):317-24. · 5.34 Impact Factor
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ABSTRACT: In this study, we show the leishmanicidal effects of a chloroform fraction (CLF) and a purified indole alkaloid obtained from crude stem extract of Peschiera australis against Leishmania amazonensis, a causative agent of cutaneous leishmaniasis in the New World. In a bioassay-guided chemical fractionation, the leishmanicidal activity in CLF completely and irreversibly inhibited promastigote growth. This fraction was also active against amastigotes in infected murine macrophages. Chemical analysis of CLF identified an iboga-type indole alkaloid coronaridine as one of its major compounds. Coronaridine showed potent antileishmanial activity, inhibiting promastigote and amastigote growth. Promastigotes and amastigotes treated with CLF or coronaridine showed pronounced alterations in their mitochondria as assessed by transmission electron microscopy.Antimicrobial Agents and Chemotherapy 06/2001; 45(5):1349-54. · 4.57 Impact Factor