Therapeutic Efficacy of <i>Arnica</i> in Hamsters with Cutaneous Leishmaniasis Caused by <i>Leishmania braziliensis</i> and <i>L. tropica</i>
Leishmaniasis may occur in three different clinical forms, namely, visceral, mucocutaneous and cutaneous, which are caused by different species of trypanosomatid protozoans of the genus <i>Leishmania</i>. Pentavalent antimonials are the leading treatment for cutaneous leishmaniasis despi...
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| Main Authors: | , , , , , , , |
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MDPI AG,
2022-06-01T00:00:00Z.
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| Summary: | Leishmaniasis may occur in three different clinical forms, namely, visceral, mucocutaneous and cutaneous, which are caused by different species of trypanosomatid protozoans of the genus <i>Leishmania</i>. Pentavalent antimonials are the leading treatment for cutaneous leishmaniasis despite the hepatic, renal, and cardiac toxicity. In addition, the response of some <i>Leishmania</i> species to pentavalent antimonials is increasingly poorer, and therefore new and more potent therapeutic alternatives are needed. <i>Arnica montana</i> L., Asteraceae, is a traditional medicinal plant of Europe and preparations of its flowers are commonly used externally to treat disorders of the musculoskeletal system as well as superficial inflammatory conditions. Previous studies have shown that Arnica tincture (AT), an ethanolic extract prepared from the flowerheads of <i>Arnica montana</i> as well as isolated Arnica sesquiterpene lactones (STLs) have antileishmanial activity in vitro against <i>L. donovani</i> and <i>L. infantum</i>, as well as in vivo against <i>L. braziliensis</i>. In this work, we studied the in vitro cytotoxicity and antileishmanial activity of AT and STLs against both <i>L. braziliensis</i> and <i>L. tropica</i>. The in vivo therapeutic effect of AT was studied in hamsters with cutaneous Leishmaniasis (CL) caused by experimental infection with <i>L. braziliensis</i> and <i>L. tropica</i>. Furthermore, various semisolid Arnica preparations were also evaluated against <i>L. braziliensis</i>. The STLs and the AT possess a very high in vitro activity against both <i>Leishmania</i> species with median effective concentrations (EC<sub>50</sub>) ranging from 1.9 to 5.9 μg/mL. The AT was not cytotoxic for human tissue macrophages, skin fibroblasts, and hepatic cells. The therapeutic response of hamsters infected with <i>L. braziliensis</i> to the topical treatment with AT was 87.5% at a dose of 19.2 μg STL/2× day/60 d, 72.7% at doses of 19.2 μg STL/1× d/60 d and 67% at a dose of 38.4 μg STL/2× d/60 d. In turn, the therapeutic response in hamsters infected with <i>L. tropica</i> was 100% when treated at a dose of 19.2 μg STL/2× day/60 d and 71% at a dose of 38.4 μg STL/2× d/60 d. On the other hand, the effectiveness of treatment with glucantime administered intralesionally at a dose of 200 mg/every three days for 30 days was 62.5% for <i>L. braziliensis</i> and 37.5% for <i>L. tropica</i> infection. These results are promising and encourage the implementation of clinical trials with AT in CL patients as a first step to using AT as a drug against CL. |
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| Item Description: | 10.3390/ph15070776 1424-8247 |