In vitro and in vivo leishmanicidal activity of Dysoxylum binectariferum and its fractions against Leishmania donovani

Phytomedicine ◽  
2007 ◽  
Vol 14 (1) ◽  
pp. 36-42 ◽  
Author(s):  
V. Lakshmi ◽  
K. Pandey ◽  
A. Kapil ◽  
N. Singh ◽  
M. Samant ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Leishmanicidal Activity ◽  
Dysoxylum Binectariferum

scholarly journals Nanotized Curcumin and Miltefosine, a Potential Combination for Treatment of Experimental Visceral Leishmaniasis

2016 ◽  
Vol 61 (3) ◽  
Author(s):  
Brajendra Tiwari ◽  
Richa Pahuja ◽  
Pradeep Kumar ◽  
Srikanta Kumar Rath ◽  
Kailash Chand Gupta ◽  
...  
Keyword(s):  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Oral Drug ◽  
Hamster Model ◽  
Content Type ◽  
Leishmanicidal Activity ◽  
Traditional Indian Medicine ◽  
Indian Medicine

ABSTRACT Leishmaniasis chemotherapy remains very challenging due to high cost of the drug and its associated toxicity and drug resistance, which develops over a period of time. Combination therapies (CT) are now in use to treat many diseases, such as cancer and malaria, since it is more effective and affordable than monotherapy. CT are believed to represent a new explorable strategy for leishmaniasis, a neglected tropical disease caused by the obligate intracellular parasite Leishmania. In the present study, we investigated the effect of a combination of a traditional Indian medicine (ayurveda), a natural product curcumin and miltefosine, the only oral drug for visceral leishmaniasis (VL) using a Leishmania donovani-hamster model. We developed an oral nanoparticle-based formulation of curcumin. Nanoformulation of curcumin alone exhibited significant leishmanicidal activity both in vitro and in vivo. In combination with miltefosine, it exhibited a synergistic effect on both promastigotes and amastigotes under in vitro conditions. The combination of these two agents also demonstrated increased in vivo leishmanicidal activity accompanied by increased production of toxic reactive oxygen/nitrogen metabolites and enhanced phagocytic activity. The combination also exhibited increased lymphocyte proliferation. The present study thus establishes the possible use of nanocurcumin as an adjunct to antileishmanial chemotherapy.

scholarly journals In Vitro and In Vivo Activities of a Triterpenoid Saponin Extract (PX-6518) from the Plant Maesa balansae against Visceral Leishmania Species

2004 ◽  
Vol 48 (1) ◽  
pp. 130-136 ◽  
Author(s):  
Louis Maes ◽  
Dirk Vanden Berghe ◽  
Nils Germonprez ◽  
Ludo Quirijnen ◽  
Paul Cos ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Human Fibroblasts ◽  
Subcutaneous Administration ◽  
Leishmania Species ◽  
Host Cells ◽  
Triterpenoid Saponin ◽  
Sodium Stibogluconate ◽  
Triterpenoid Saponins

ABSTRACT The in vitro and in vivo activities of a mixture of six oleane triterpene saponins, recovered from the methanolic extract of the leaves of the Vietnamese plant Maesa balansae (PX-6518), were evaluated against drug-sensitive visceral Leishmania strains. The in vitro 50% inhibitory concentration (IC50) against intracellular Leishmania infantum amastigotes was 0.04 μg/ml. The cytotoxic concentrations causing 50% cell death (CC50s) were about 1 μg/ml in murine macrophage host cells and >32 μg/ml in human fibroblasts (MRC-5 cell line). Evaluation in the Leishmania donovani BALB/c mouse model indicated that a single subcutaneous administration of 0.4 mg/kg at 1 day after infection reduced liver amastigote burdens by about 95% in all treated animals. If treatment was delayed until 14 days after infection, a dose of 1.6 mg/kg of body weight was required to maintain the same level of activity. Single 250-mg/kg doses of sodium stibogluconate (Pentostam) 1 and 14 days after infection produced comparable efficacies. A single dose of PX-6518 at 2.5 mg/kg administered 5 days before infection was still 100% effective in preventing liver infection, suggesting a particularly long residual action. Spleen and bone marrow could not be cleared by PX-6518 nor sodium stibogluconate. PX-6518 did not show activity after oral dosing at up to 200 mg/kg for 5 days. This study concludes that triterpenoid saponins from M. balansae show promising in vitro and in vivo antileishmanial potential and can be considered as new lead structures in the search for novel antileishmanial drugs.

scholarly journals Antiparasitary Activity Of The Juglone Compound: A Narrative Review

2021 ◽  
pp. 13
Author(s):  
◽  
Keyword(s):  
Mortality Rate ◽  
Leishmania Donovani ◽  
Inhibitory Concentration ◽  
Narrative Review ◽  
Hymenolepis Nana ◽  
Compound A ◽  
Living Organisms ◽  
Nanomolar Range

Objective: To report, based on the literature, the action of the compound 5-hydroxy-1,4-naphthoquinone against parasites (protozoa and helminths) that affect humans. Methods: This is a narrative review that used Pubmed and Google Scholar as a data tool. This work included articles published until September 2020 that were directly related to the use of the compound juglone in antiparasitic trials. Results: The compound juglone demonstrated promising effects as a human and animal antiparasitic substance. In protozoa, the Apicomplexo Toxoplasma gondii parasite showed a high mortality rate in concentrations of juglone in the nanomolar range. The juglone showed an average inhibitory concentration (IC50) of 1.62 µM, >100 µM, and 2.02 µM µM for Trypanosoma cruzi, T. brucei rhodesiense, and Leishmania donovani, respectively. Also, the juglone showed antihelmintic activity on Hymenolepis nana in mice, and on adult worms of Schistosoma mansoni (LE strain) with IC50 34.16 µM, 32.14 µM, and 25 µM in the 24h, 48h, and 72 h, respectively. Conclusion: The results published so far show the in vitro antiparasitic potential of juglone, and the need for further studies on the specific mode of action that interacts with parasites. Besides, the literature is still limited to studies that evaluate in vivo the compound juglone, requiring better information on its interaction with living organisms.

scholarly journals TCP1γ Subunit Is Indispensable for Growth and Infectivity of Leishmania donovani

2020 ◽  
Vol 64 (8) ◽  
Author(s):  
Shailendra Yadav ◽  
Jitendra Kuldeep ◽  
Mohammad I. Siddiqi ◽  
Neena Goyal
Keyword(s):  
Cell Cycle Progression ◽  
Leishmania Donovani ◽  
Gene Replacement ◽  
Titration Calorimetry ◽  
Content Type ◽  
T Complex ◽  
Complex Protein ◽  
Oligomeric Complex

ABSTRACT T-complex protein-1 (TCP1) is a ubiquitous group II chaperonin and is known to fold various proteins, such as actin and tubulin. In Leishmania donovani, the γ subunit of TCP1 (LdTCP1γ) has been cloned and characterized. It forms a high-molecular-weight homo-oligomeric complex that performs ATP-dependent protein folding. In the present study, we evaluated the essentiality of the LdTCP1γ gene. Gene replacement studies indicated that LdTCP1γ is essential for parasite survival. The LdTCP1γ single-allele-replacement mutants exhibited slowed growth and decreased infectivity in mouse macrophages compared to the growth and infectivity of the wild-type parasites. Modulation of LdTCP1γ expression in promastigotes also modulated cell cycle progression. Suramin, an antitrypanosomal drug, not only inhibited the luciferase refolding activity of the recombinant LdTCP1γ (rLdTCP1γ) homo-oligomeric complex but also exhibited potential antileishmanial efficacy both in vitro and in vivo. The interaction of suramin and LdTCP1γ was further validated by isothermal titration calorimetry. The study suggests LdTCP1γ as a potential drug target and also provides a framework for the development of a new class of drugs.

In vitro and in vivo Activities of Three Acridine Thioethers against Leishmania donovani

Pharmacology ◽  
2002 ◽  
Vol 65 (2) ◽  
pp. 74-82 ◽  
Author(s):  
Concepción Mesa ◽  
Nieves Rodriguez-Cabezas ◽  
Juan J. Castilla ◽  
Valentín Moraleda-Lindez ◽  
Jacques Barbe ◽  
...  
Keyword(s):  
Leishmania Donovani

scholarly journals In vitro and in vivo immunomodulatory properties of octyl-β-d-galactofuranoside during Leishmania donovani infection

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Hélène Guegan ◽  
Kevin Ory ◽  
Sorya Belaz ◽  
Aurélien Jan ◽  
Sarah Dion ◽  
...  
Keyword(s):  
Immune Response ◽  
Leishmania Donovani ◽  
Parasite Burden ◽  
Human Monocyte ◽  
Fold Increase ◽  
Control Group ◽  
End Of Treatment ◽  
Immunosuppressed Patients

Abstract Background The chemotherapeutic arsenal available to treat visceral leishmaniasis is currently limited, in view of many drawbacks such as high cost, toxicity or emerging resistance. New therapeutic strategies are particularly needed to improve the management and the outcome in immunosuppressed patients. The combination of an immunomodulatory drug to a conventional anti-Leishmania treatment is an emerging concept to reverse the immune bias from Th2 to Th1 response to boost healing and prevent relapses. Methods Here, immunostimulating and leishmanicidal properties of octyl-β-d-galactofuranose (Galf) were assessed in human monocyte-derived macrophages (HM) and in a murine model, after challenge with Leishmania donovani promastigotes. We recorded parasite loads and expression of various cytokines and immune effectors in HM and mouse organs (liver, spleen, bone marrow), following treatment with free (Galf) and liposomal (L-Galf) formulations. Results Both treatments significantly reduced parasite proliferation in HM, as well as liver parasite burden in vivo (Galf, P < 0.05). Consistent with in vitro results, we showed that Galf- and L-Galf-treated mice displayed an enhanced Th1 immune response, particularly in the spleen where pro-inflammatory cytokines TNF-α, IL-1β and IL-12 were significantly overexpressed compared to control group. The hepatic recruitment of myeloid cells was also favored by L-Galf treatment as evidenced by the five-fold increase of myeloperoxidase (MPO) induction, which was associated with a higher number of MPO-positive cells within granulomas. By contrast, the systemic level of various cytokines such as IL-1β, IL-6, IL-17A or IL-27 was drastically reduced at the end of treatment. Conclusions Overall, these results suggest that Galf could be tested as an adjuvant in combination with current anti-parasitic drugs, to restore an efficient immune response against infection in a model of immunosuppressed mice.

Leishmania donovani infection of bone marrow stromal macrophages selectively enhances myelopoiesis, by a mechanism involving GM-CSF and TNF-α

Blood ◽  
2000 ◽  
Vol 95 (5) ◽  
pp. 1642-1651 ◽  
Author(s):  
Sara E. J. Cotterell ◽  
Christian R. Engwerda ◽  
Paul M. Kaye
Keyword(s):  
Infectious Disease ◽  
Bone Marrow ◽  
Stromal Cell ◽  
Leishmania Donovani ◽  
Protozoan Parasite ◽  
Gm Csf ◽  
Tnf Α ◽  
Macrophage Colony

Alterations in hematopoiesis are common in experimental infectious disease. However, few studies have addressed the mechanisms underlying changes in hematopoietic function or assessed the direct impact of infectious agents on the cells that regulate these processes. In experimental visceral leishmaniasis, caused by infection with the protozoan parasite Leishmania donovani, parasites persist in the spleen and bone marrow, and their expansion in these sites is associated with increases in local hematopoietic activity. The results of this study show that L donovani targets bone marrow stromal macrophages in vivo and can infect and multiply in stromal cell lines of macrophage, but not other lineages in vitro. Infection of stromal macrophages increases their capacity to support myelopoiesis in vitro, an effect mediated mainly through the induction of granulocyte macrophage-colony stimulating factor and tumor necrosis factor-. These data are the first to directly demonstrate that intracellular parasitism of a stromal cell population may modify its capacity to regulate hematopoiesis during infectious disease.

In vitro and in vivo Activity of Two Pt(IV) Salts against Leishmania donovani

Pharmacology ◽  
1998 ◽  
Vol 57 (3) ◽  
pp. 160-172 ◽  
Author(s):  
C.M. Mesa-Valle ◽  
M.N. Rodriguez-Cabezas ◽  
V. Moraleda-Lindez ◽  
D. Craciunescu ◽  
M. Sanchez-Moreno ◽  
...  
Keyword(s):  
Leishmania Donovani

scholarly journals In vitro and in vivo antileishmanial efficacy of a combination therapy of diminazene and artesunate against Leishmania donovani in BALB/c mice

2011 ◽  
Vol 53 (3) ◽  
pp. 129-132 ◽  
Author(s):  
Joshua Muli Mutiso ◽  
John Chege Macharia ◽  
Mustafa Barasa ◽  
Evans Taracha ◽  
Alain J. Bourdichon ◽  
...  
Keyword(s):  
Leishmania Donovani ◽  
Combined Therapy ◽  
Parasite Burden ◽  
Mice Model ◽  
In Vivo Evaluation ◽  
Reference Drug ◽  
Drug Treatments ◽  
Potential Use

The in vitro and in vivo activity of diminazene (Dim), artesunate (Art) and combination of Dim and Art (Dim-Art) against Leishmania donovani was compared to reference drug; amphotericin B. IC50 of Dim-Art was found to be 2.28 ± 0.24 µg/mL while those of Dim and Art were 9.16 ± 0.3 µg/mL and 4.64 ± 0.48 µg/mL respectively. The IC50 for Amphot B was 0.16 ± 0.32 µg/mL against stationary-phase promastigotes. In vivo evaluation in the L. donovani BALB/c mice model indicated that treatments with the combined drug therapy at doses of 12.5 mg/kg for 28 consecutive days significantly (p < 0.001) reduced parasite burden in the spleen as compared to the single drug treatments given at the same dosages. Although parasite burden was slightly lower (p < 0.05) in the Amphot B group than in the Dim-Art treatment group, the present study demonstrates the positive advantage and the potential use of the combined therapy of Dim-Art over the constituent drugs, Dim or Art when used alone. Further evaluation is recommended to determine the most efficacious combination ratio of the two compounds.

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