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      Antileishmanial activity of a mixture ofTridax procumbensandAllium sativumin mice

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          Abstract

          We tested a mixture of Tridax procumbens, known for its direct action against Leishmania mexicana, and Allium sativum, known for its immunomodulatory effect, as an alternative to treat cutaneous leishmaniasis. Acute oral toxicity was tested with the Up-and-Down Procedure (UDP) using a group of healthy mice administered with either T. procumbens or A. sativum extracts and compared with a control group. Liver injury and other parameters of toxicity were determined in mice at day 14. The in vivo assay was performed with mice infected with L. mexicana promastigotes and treated with either a mixture of T. procumbens and A. sativum or each extract separately. The thickness of the mice’s footpads was measured weekly. After the 12-week period of infection, blood samples were obtained by cardiac puncture to determine the total IgG, IgG1 and IgG2a immunoglobulins by a noncommercial indirect ELISA. We showed that the mixture of T. procumbens and A. sativum extracts was better at controlling L. mexicana infection while not being toxic when tested in the acute oral toxicity assay in mice. An increase in the ratio of IgG2a/IgG1 indicated a tendency to raise a Th1-type immune response in mice treated with the mixture. The mixture of T. procumbens and A. sativum extracts is a promising natural treatment for cutaneous leishmaniasis and its healing effects make it a good candidate for a possible new phytomedicine.

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          Most cited references22

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          Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance.

          Miltefosine (MIL), the only oral drug for visceral leishmaniasis (VL), is currently the first-line therapy in the VL elimination program of the Indian subcontinent. Given the paucity of anti-VL drugs and the looming threat of resistance, there is an obvious need for close monitoring of clinical efficacy of MIL. In a cohort study of 120 VL patients treated with MIL in Nepal, we monitored the clinical outcomes up to 12 months after completion of therapy and explored the potential role of drug compliance, parasite drug resistance, and reinfection. The initial cure rate was 95.8% (95% confidence interval [CI], 92.2-99.4) and the relapse rate at 6 and 12 months was 10.8% (95% CI, 5.2-16.4) and 20.0% (95% CI, 12.8-27.2) , respectively. No significant clinical risk factors of relapse apart from age <12 years were found. Parasite fingerprints of pretreatment and relapse bone marrow isolates within 8 patients were similar, suggesting that clinical relapses were not due to reinfection with a new strain. The mean promastigote MIL susceptibility (50% inhibitory concentration) of isolates from definite cures was similar to that of relapses. Although more tolerant strains were observed, parasite resistance, as currently measured, is thus not likely involved in MIL treatment failure. Moreover, MIL blood levels at the end of treatment were similar in cured and relapsed patients. Relapse in one-fifth of the MIL-treated patients observed in our study is an alarming signal for the VL elimination campaign, urging for further review and cohort monitoring.
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            Cross-protective efficacy of a prophylactic Leishmania donovani DNA vaccine against visceral and cutaneous murine leishmaniasis.

            The fucose-mannose ligand (FML) complex of Leishmania donovani is a promising vaccine candidate against murine and canine visceral leishmaniasis, and its main component is a 36-kDa nucleoside hydrolase (NH36). In this study, we tested the immune response and protection induced by the purified FML, the recombinant NH36 (rNH36), and NH36 DNA vaccines against the agents of visceral (L. chagasi) and cutaneous (L. mexicana) leishmaniasis in BALB/c mice. Mice developed weak humoral response to the vaccines alone, except for those immunized with FML. However, all three vaccine groups presented elevated immunoglobulin G (IgG), IgG1, and IgG2a levels after infection with L. chagasi, whereas no differences were observed between vaccine and control groups after infection with L. mexicana. A strong intradermal reaction to L. donovani and L. mexicana antigens was observed in mice immunized with rNH36 or FML, whereas mice immunized with NH36 DNA only reacted against L. donovani antigens. Experimental infection of immunized mice demonstrated that FML and rNH36 induced significant protection against L. chagasi infection with reductions in parasite loads of 79%. FML also conferred partial protection against L. mexicana infection. The best protection was observed in mice immunized with the VR1012-NH36 DNA vaccine, which induced an 88% reduction in L. chagasi parasite load and a 65% reduction in L. mexicana lesion size. Fluorescence-activated cell sorting analysis indicated the DNA vaccine induced a two- to fivefold increase in gamma interferon-producing CD4(+) T cells, indicating a Th1-type immune response. Our results showed that the NH36 DNA vaccine induced a strong immunoprotection against visceral and cutaneous leishmaniasis, suggesting that this DNA vaccine represents a very good candidate for use against several Leishmania species.
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              In vitro antiprotozoal activity of extract and compounds from the stem bark of Combretum molle.

              The antiprotozoal activity of the Ethiopian medicinal plant Combretum molle (R. Br. ex G. Don.) Engl & Diels (Combretaceae) was evaluated by in vitro testing against Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani. The acetone fraction of the stem bark of this plant prepared by soxhlet extraction was inactive against the intracellular amastigotes of L. donovani and T. cruzi in murine peritoneal macrophages but showed significant activity against extracellular T. b. rhodesiense blood stream form trypomastigotes and trophozoites of P. falciparum with IC(50) values of 2.19 and 8.17 microg/mL, respectively. Phytochemical examination of the bioactive fraction resulted in the isolation of two tannins and two oleanane-type pentacyclic triterpene glycosides. One of the tannins was identified as the ellagitannin, punicalagin, whilst the structure of the other (CM-A) has not yet been fully elucidated. The saponins that were characterized as arjunglucoside (also called 4-epi-sericoside) and sericoside displayed no activity against any of the four species of protozoa tested. On the other hand, punicalagin and CM-A had IC(50) values of 1.75 and 1.50 microM, respectively, against T. b. rhodesiense and were relatively less toxic to KB cells (cytotoxic/antiprotozoal ratios of 70 and 48, respectively). The tannins also showed intermediate activity against P. falciparum, although their selectivity against these parasites was less favourable than the above. It appears that our findings are the first report of hydrolysable tannins exhibiting antitrypanosomal and antiplasmodial activities. Copyright 2001 John Wiley & Sons, Ltd.
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                Author and article information

                Journal
                Parasite
                Parasite
                EDP Sciences
                1776-1042
                2014
                April 2014
                : 21
                :
                : 15
                Article
                10.1051/parasite/2014016
                57e17dec-6523-4439-a999-a04d7a461698
                © 2014

                This work is licensed under a Creative Commons Attribution 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History

                Parasitology,Life sciences
                Parasitology, Life sciences

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