Activity of physalins purified from Physalis angulata in in vitro and in vivo models of cutaneous leishmaniasis.
ABSTRACT We have previously demonstrated the immunomodulatory effects of physalins, secosteroids purified from Physalis angulata. Here we investigate the antileishmanial activity of physalins in vitro and in vivo in a model of cutaneous leishmaniasis.
The antileishmanial activity of physalins B, D and F was tested in Leishmania-infected macrophage cultures. For the in vivo studies, BALB/c mice were infected with Leishmania amazonensis subcutaneously in the ear pinna and treated with physalin F by topical administration.
Physalins B and F were able to reduce the percentage of Leishmania-infected macrophages and the intracellular parasite number in vitro at concentrations non-cytotoxic to macrophages. More importantly, topical treatment with physalin F significantly reduced the lesion size, the parasite load and histopathological alterations in BALB/c mice infected with L. amazonensis.
Our results demonstrate the potent antileishmanial activity of physalins, especially physalin F, and suggest these molecules as the basis for the development of new therapeutic options for cutaneous leishmaniasis.
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ABSTRACT: Diseases caused by insect borne trypanosomatid parasites are significant, yet remain a neglected public health problem. Leishmania, a unicellular protozoan parasite is the causative organism of Leishmaniasis and is transmitted by female phlebotamine sandflies affecting millions of people worldwide. In the wake of resistance to pentavalent antimonial drugs, new therapeutic alternatives are desirable. The plant kingdom has in the past provided several affordable compounds and this review aims to provide an overview of the current status of available leishmanicidal plant derived compounds that are effective singly or in combination with conventional anti-leishmanial drugs, yet are non toxic to mammalian host cells. Furthermore, delineation of the contributory biochemical mechanisms involved in mediating their effect would help develop new chemotherapeutic approaches.Phytomedicine: international journal of phytotherapy and phytopharmacology 05/2011; 18(12):1056-69. · 2.97 Impact Factor
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ABSTRACT: Antileishmanial in vitro tests, as well as Ames and micronucleus assays were performed with a concentrated ethanolic extract of Physalis angulata (EEPA) RESULTS: EEPA did not present mutagenic effect in Salmonella typhimurium strains at concentration reaching 3000μg/plate and did not induce mutagenic effects after two oral administrations with a 24h interval at a dose level of 2000mg/kg. EEPA presented antileishmanial activity and presented an IC50 value of 5.35±2.50μg/mL and 4.50±1.17μg/mL against Leishmania amazonensis and Leishmania braziliensis promastigotes, respectively. In the cytotoxicity test against macrophages, the EEPA had a LC50 of 6.14±0.59μg/mL. Importantly, the IC50 against L. amazonensis intracellular amastigotes was 1.23±0.11μg/mL. EEPA extract is non-mutagenic and presented a promising pharmacological effect against Leishmania parasites.Environmental toxicology and pharmacology. 10/2013; 36(3):1304-1311.
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ABSTRACT: Physalin B is a natural secosteroidal, extracted from the Solanaceae plant, Physalis angulata, and it presents immune-modulator effects on the bloodsucking bug, Rhodnius prolixus. In this work, R. prolixus was treated with physalin B at a concentration of 1mg/ml of blood meal (oral application), or 20ng/insect (applied topically) or 57ng/cm(2) of filter paper (contact treatment), and infected with Trypanosoma cruzi Dm28c clone (2×10(6) epimastigotes/insect). The three types of applications significantly decreased the number of T. cruzi Dm28c in the gut comparing with the non-treated infected insects (controls). All groups of infected insects treated with physalin B had higher numbers of bacterial microbiota in the gut than the non-treated controls infected with T. cruzi. We observed that the infected physalin B insects with topical and contact treatments had a lower antibacterial activity in the gut when compared with control infected insects. Furthermore, infected insects with the physalin B oral treatment produced higher levels of nitrite and nitrate in the gut than control infected insects. These results demonstrate that physalin B decreases the T. cruzi transmission by inhibiting the parasite development in the insect vector R. prolixus. Herein the importance of physalin B modulation on the immune system and microbiota population in terms of parasite development and transmission are discussed.Journal of insect physiology 10/2012; · 2.24 Impact Factor