scholarly journals In VitroandIn VivoEfficacy of Novel Flavonoid Dimers against Cutaneous Leishmaniasis

2014 ◽  
Vol 58 (6) ◽  
pp. 3379-3388 ◽  
Author(s):  
Iris L. K. Wong ◽  
Kin-Fai Chan ◽  
Yun-Fu Chen ◽  
Zhao-Rong Lun ◽  
Tak Hang Chan ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Donovani ◽  
Leishmania Major ◽  
Leishmania Braziliensis ◽  
Leishmania Tropica ◽  
Content Type ◽  
New Class ◽  
Limited Efficacy ◽  
Intralesional Administration ◽  
Subcutaneous Inoculation

ABSTRACTTreatment of leishmaniasis by chemotherapy remains a challenge because of limited efficacy, toxic side effects, and drug resistance. We previously reported that synthetic flavonoid dimers have potent antipromastigote and antiamastigote activity againstLeishmania donovani, the causative agent of visceral leishmaniasis. Here, we further investigate their leishmanicidal activities against cutaneousLeishmaniaspecies. One of the flavonoid dimers (compound 39) has marked antipromastigote (50% inhibitory concentrations [IC50s], 0.19 to 0.69 μM) and antiamastigote (IC50s, 0.17 to 2.2 μM) activities toward different species ofLeishmaniathat cause cutaneous leishmaniasis, includingLeishmania amazonensis,Leishmania braziliensis,Leishmania tropica, andLeishmania major. Compound 39 is not toxic to peritoneal elicited macrophages, with IC50values higher than 88 μM. In the mouse model of cutaneous leishmaniasis induced by subcutaneous inoculation ofL. amazonensisin mouse footpads, intralesional administration of 2.5 mg/kg of body weight of compound 39.HCl can reduce footpad thickness by 36%, compared with that of controls values. The amastigote load in the lesions was reduced 20-fold. The present study suggests that flavonoid dimer 39 represents a new class of safe and effective leishmanicidal agent against visceral and cutaneous leishmaniasis.

Leishmanicidal Activity of Plant Extracts from Sefrou, a Moroccan Focus of Leishmaniasis, against Various Leishmania Parasites in the Promastigote Stage

2018 ◽  
Vol 17 (2) ◽  
pp. 83-89 ◽  
Author(s):  
I. Zeouk ◽  
A. Et-Touys ◽  
M. Balouiri ◽  
H. Fellah ◽  
A. El Ouali Lalami ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Plant Extracts ◽  
Leishmania Infantum ◽  
Leishmania Major ◽  
Local Population ◽  
Public Health Problem ◽  
World Health ◽  
Total Phenolic ◽  
Leishmania Tropica ◽  
Cistus Salviifolius

According to the World Health Organization, leishmaniasis remains a major worldwide public health problem. The province of Sefrou located in the center of Morocco is a focus of cutaneous leishmaniasis. The present study aims at evaluating the antileishmanial potential of Berberis sp.,Crataegus oxyacantha, Cistus salviifolius, Ephedra altissima and Lavandula dentatafrequently used by the local population. Methanolic extracts were tested against the promastigote form ofLeishmania tropica, Leishmania majorandLeishmania infantumusing tetrazolium-based colorimetric (MTT) assay. The total phenol and flavonoids content of all extracts were determined using the Folin–Ciocalteu reagent, aluminum chloride, and potassium acetate solutions respectively. The plant extracts exhibited antileishmanial activity with variability depending on the tested strain and the plant species compared to Glucantime® used as control (IC50 (the half maximal inhibitory concentration) > 1,000 μg/mL). The best inhibition was observed with Berberis sp., againstLeishmania major(IC50 = 394.40 ± 3.02 μg/ml), andEphedra altissima(reported for the first time) againstLeishmania infantum(IC50 = 490.84 ± 3.15 μg/mL).Leishmania tropicahas shown the same sensitivity behavior toward the five extracts (in average IC50 = 540 ± 11.20 μg/mL). The total phenolic content was higher forCrataegus oxyacanthaandCistus salviifolius(140.67 ± 3.17 μg eq Gallic Acid (GA)/ mg of Extract (E) and 133.83 ± 9.03 μg eq GA/mg of E respectively), while flavonoid was higher forCistus salviifoliusandLavandula dentata(57.92 ± 2.46 μg eq Quercetin (Que)/ mg of Extract (E) and 41.53 ± 1.74 μg eq Que/mg of E). All the tested extracts present some promising aspects that may cure cutaneous leishmaniasis in the center of Morocco; further bioguided assays are needed to isolate the fractions and the bioactive molecule.

scholarly journals EAPB0503: an imiquimod analog with potent in vitro activity against cutaneous leishmaniasis caused by Leishmania major and Leishmania tropica

2020 ◽  
Vol 13 (12) ◽  
pp. 2112
Author(s):  
Rana El Hajj ◽  
Hanady Bou Youness ◽  
Laurence Lachaud ◽  
Patrick Bastien ◽  
Carine Masquefa ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Vitro Activity ◽  
Leishmania Tropica ◽  
In Vitro Activity

Inhibition by Dications of In Vitro Growth of Leishmania major and Leishmania tropica: Causative Agents of Old World Cutaneous Leishmaniasis

2008 ◽  
Vol 94 (3) ◽  
pp. 743-749 ◽  
Author(s):  
Alexa C. Rosypal ◽  
Karl A. Werbovetz ◽  
Manar Salem ◽  
Chad E. Stephens ◽  
Arvind Kumar ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Leishmania Tropica ◽  
In Vitro Growth ◽  
Old World ◽  
Causative Agents

scholarly journals EAPB0503: An Imiquimod analog with potent in vitro activity against cutaneous leishmaniasis caused by Leishmania major and Leishmania tropica

2018 ◽  
Vol 12 (11) ◽  
pp. e0006854 ◽  
Author(s):  
Rana El Hajj ◽  
Hanady Bou Youness ◽  
Laurence Lachaud ◽  
Patrick Bastien ◽  
Carine Masquefa ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Vitro Activity ◽  
Leishmania Tropica ◽  
In Vitro Activity

scholarly journals Expression of Inducible Nitric Oxide Synthase in Skin Lesions of Patients with American Cutaneous Leishmaniasis

2002 ◽  
Vol 70 (8) ◽  
pp. 4638-4642 ◽  
Author(s):  
Muna Qadoumi ◽  
Inge Becker ◽  
Norbert Donhauser ◽  
Martin Röllinghoff ◽  
Christian Bogdan
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Donovani ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Skin Lesions ◽  
And Function ◽  
Oxide Synthase

ABSTRACT Cytokine-inducible (or type 2) nitric oxide synthase (iNOS) is indispensable for the resolution of Leishmania major or Leishmania donovani infections in mice. In contrast, little is known about the expression and function of iNOS in human leishmaniasis. Here, we show by immunohistological analysis of skin biopsies from Mexican patients with local (LCL) or diffuse (DCL) cutaneous leishmaniasis that the expression of iNOS was most prominent in LCL lesions with small numbers of parasites whereas lesions with a high parasite burden (LCL or DCL) contained considerably fewer iNOS-positive cells. This is the first study to suggest an antileishmanial function of iNOS in human Leishmania infections in vivo.

Inhibition by Dications of In Vitro Growth of Leishmania major and Leishmania tropica: Causative Agents of Old World Cutaneous Leishmaniasis

2008 ◽  
Vol 94 (3) ◽  
pp. 743 ◽  
Author(s):  
Alexa C. Rosypal ◽  
Karl A. Werbovetz ◽  
Manar Salem ◽  
Chad E. Stephens ◽  
Arvind Kumar ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Leishmania Tropica ◽  
In Vitro Growth ◽  
Old World ◽  
Causative Agents

scholarly journals Zinc(II)-Dipicolylamine Coordination Complexes as Targeting and Chemotherapeutic Agents for Leishmania major

2016 ◽  
Vol 60 (5) ◽  
pp. 2932-2940 ◽  
Author(s):  
Douglas R. Rice ◽  
Paola Vacchina ◽  
Brianna Norris-Mullins ◽  
Miguel A. Morales ◽  
Bradley D. Smith
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Mammalian Cells ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Coordination Complexes ◽  
Chemotherapeutic Agents ◽  
Selective Toxicity ◽  
Content Type

ABSTRACTCutaneous leishmaniasis is a neglected tropical disease that causes painful lesions and severe disfigurement. Modern treatment relies on a few chemotherapeutics with serious limitations, and there is a need for more effective alternatives. This study describes the selective targeting of zinc(II)-dipicolylamine (ZnDPA) coordination complexes towardLeishmania major, one of the species responsible for cutaneous leishmaniasis. Fluorescence microscopy ofL. majorpromastigotes treated with a fluorescently labeled ZnDPA probe indicated rapid accumulation of the probe within the axenic promastigote cytosol. The antileishmanial activities of eight ZnDPA complexes were measured using anin vitroassay. All tested complexes exhibited selective toxicity againstL. majoraxenic promastigotes, with 50% effective concentration values in the range of 12.7 to 0.3 μM. Similar toxicity was observed against intracellular amastigotes, but there was almost no effect on the viability of mammalian cells, including mouse peritoneal macrophages.In vivotreatment efficacy studies used fluorescence imaging to noninvasively monitor changes in the red fluorescence produced by an infection of mCherry-L. majorin a mouse model. A ZnDPA treatment regimen reduced the parasite burden nearly as well as the reference care agent, potassium antimony(III) tartrate, and with less necrosis in the local host tissue. The results demonstrate that ZnDPA coordination complexes are a promising new class of antileishmanial agents with potential for clinical translation.

scholarly journals Transgenic Expression of CXCR3 on T Cells Enhances Susceptibility to Cutaneous Leishmania major Infection by Inhibiting Monocyte Maturation and Promoting a Th2 Response

2014 ◽  
Vol 83 (1) ◽  
pp. 67-76 ◽  
Author(s):  
Steve Oghumu ◽  
James C. Stock ◽  
Sanjay Varikuti ◽  
Ran Dong ◽  
Cesar Terrazas ◽  
...  
Keyword(s):  
T Cells ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Critical Role ◽  
Sand Fly ◽  
Interleukin 4 ◽  
Th2 Response ◽  
Content Type ◽  
Transgenic Expression ◽  
Inflammatory Monocytes

Cutaneous leishmaniasis, caused mainly byLeishmania major, an obligate intracellular parasite, is a disfiguring disease characterized by large skin lesions and is transmitted by a sand fly vector. We previously showed that the chemokine receptor CXCR3 plays a critical role in mediating resistance to cutaneous leishmaniasis caused byLeishmania major. Furthermore, T cells fromL. major-susceptible BALB/c but notL. major-resistant C57BL/6 mice fail to efficiently upregulate CXCR3 upon activation. We therefore examined whether transgenic expression of CXCR3 on T cells would enhance resistance toL. majorinfection in susceptible BALB/c mice. We generated BALB/c and C57BL/6 transgenic mice, which constitutively overexpressed CXCR3 under a CD2 promoter, and then examined the outcomes withL. majorinfection. Contrary to our hypothesis, transgenic expression of CXCR3 (CXCR3Tg) on T cells of BALB/c mice resulted in increased lesion sizes and parasite burdens compared to wild-type (WT) littermates afterL. majorinfection. Restimulated lymph node cells fromL. major-infected BALB/c-CXCR3Tgmice produced more interleukin-4 (IL-4) and IL-10 and less gamma interferon (IFN-γ). Cells in draining lymph nodes from BALB/c-CXCR3Tgmice showed enhanced Th2 and reduced Th1 cell accumulation associated with increased neutrophils and inflammatory monocytes. However, monocytes displayed an immature phenotype which correlated with increased parasite burdens. Interestingly, transgenic expression of CXCR3 on T cells did not impact the outcome ofL. majorinfection in C57BL/6 mice, which mounted a predominantly Th1 response and spontaneously resolved their infection similar to WT littermates. Our findings demonstrate that transgenic expression of CXCR3 on T cells increases susceptibility of BALB/c mice toL. major.

scholarly journals Relation between Skin Pharmacokinetics and Efficacy in AmBisome Treatment of Murine Cutaneous Leishmaniasis

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Gert-Jan Wijnant ◽  
Katrien Van Bocxlaer ◽  
Vanessa Yardley ◽  
Andy Harris ◽  
Sudaxshina Murdan ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Parasite Load ◽  
Lesion Size ◽  
Clear Correlation ◽  
Relative Reduction ◽  
Multiple Dosing ◽  
Content Type ◽  
Drug Levels ◽  
Skin Pharmacokinetics

ABSTRACTAmBisome (LAmB), a liposomal formulation of amphotericin B (AmB), is a second-line treatment for the parasitic skin disease cutaneous leishmaniasis (CL). Little is known about its tissue distribution and pharmacodynamics to inform clinical use in CL. Here, we compared the skin pharmacokinetics of LAmB with those of the deoxycholate form of AmB (DAmB; trade name Fungizone) in murine models ofLeishmania majorCL. Drug levels at the target site (the localized lesion) 48 h after single intravenous (i.v.) dosing of the individual AmB formulations (1 mg/kg of body weight) were similar but were 3-fold higher for LAmB than for DAmB on day 10 after multiple administrations (1 mg/kg on days 0, 2, 4, 6, and 8). After single and multiple dosing, intralesional concentrations were 5- and 20-fold, respectively, higher than those in the healthy control skin of the same infected mice. We then evaluated how drug levels in the lesion after LAmB treatment relate to therapeutic outcomes. After five administrations of the drug at 0, 6.25, or 12.5 mg/kg (i.v.), there was a clear correlation between dose level, intralesional AmB concentration, and relative reduction in parasite load and lesion size (R2values of >0.9). This study confirms the improved efficacy of the liposomal over the deoxycholate AmB formulation in experimental CL, which is related to higher intralesional drug accumulation.

scholarly journals Molecular characterization of Leishmania tropica and Leishmania major from stray dogs and patients in Saudi Arabia

2020 ◽  
Author(s):  
Abdullah D Alanazi ◽  
Abdulazi S Alouffi S Alouffi ◽  
Mohamed S Alyousif S Alyousif ◽  
Abdulsadah A Rahi ◽  
Magda A Ali ◽  
...  
Keyword(s):  
Saudi Arabia ◽  
Cutaneous Leishmaniasis ◽  
Nested Pcr ◽  
Leishmania Major ◽  
Sand Fly ◽  
Human Populations ◽  
Leishmania Tropica ◽  
Stray Dogs ◽  
Wild Canids ◽  
Control And Prevention

Abstract Background: Leishmania major and Leishmania tropica cause cutaneous leishmaniasis in humans and dogs in several parts of the world, with a large number of cases recorded in the Middle East. However, when occurring in sympatry, the role of each species of Leishmania in the epidemiology of cutaneous leishmaniasis (CL) is not clear. Methods: To determine the prevalence and to identify the species of Leishmania that infects humans and stray dogs in Riyadh and Al-Qassim (Saudi Arabia), 311 stray dogs and 27 human patients, suspected for Leishmania, were examined for CL by a nested PCR (nPCR).Results: Nested PCR (nPCR) detected seven patients (25.9%) positive for cutaneous leishmaniasis. Five patients from Riyadh were infected by L. major and two from Al-Qassim by L. tropica. In addition, five dogs (1.6%) were infected by L. tropica. Conclusions: This is one of the first molecular studies of leishmaniasis from Saudi Arabia. The relationship between the sand fly vectors and the reservoirs of both Leishmania spp. is still scarcely known in this region, and further epidemiological investigations of domestic and wild canids infected with L. major and L. tropica are needed towards a control and prevention of the infection in canine and human populations.

Sign in / Sign up

Export Citation Format

Share Document