Publications by authors named "Ivone M Ribeiro"

9 Publications

  • Page 1 of 1

Physalin F, a seco-steroid from Physalis angulata L., has immunosuppressive activity in peripheral blood mononuclear cells from patients with HTLV1-associated myelopathy.

Biomed Pharmacother 2016 Apr 19;79:129-34. Epub 2016 Feb 19.

Gonçalo Moniz Research Center-CPqGM/FIOCRUZ, Salvador, Bahia, Brazil; Bahiana School of Medicine and Public Health, Salvador, Bahia, Brazil. Electronic address:

Human T-lymphotropic virus type 1 (HTLV-1) induces a strong activation of the immune system, especially in individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Physalin F is a secosteroid with potent anti-inflammatory and immunomodulatory activities. The present study aimed to investigate the effects of physalin F on peripheral blood mononuclear cells (PBMC) of HAM/TSP subjects. A concentration-dependent inhibition of spontaneous proliferation of PBMC from HAM/TSP subjects was observed in the presence of physalin F, as evaluated by (3)H-thymidine uptake. The IC50 for physalin F was 0.97 ± 0.11 μM. Flow cytometry analysis using Cytometric Bead Array (CBA) showed that physalin F (10 μM) significantly reduced the levels of IL-2, IL-6, IL-10, TNF-α and IFN-γ, but not IL-17A, in supernatants of PBMC cultures. Next, apoptosis induction was addressed by using flow cytometry to evaluate annexin V expression. Treatment with physalin F (10 μM) increased the apoptotic population of PBMC in HAM/TSP subjects. Transmission electron microscopy analysis of PBMC showed that physalin F induced ultrastructural changes, such as pyknotic nuclei, damaged mitochondria, enhanced autophagic vacuole formation, and the presence of myelin-like figures. In conclusion, physalin F induces apoptosis of PBMC, decreasing the spontaneous proliferation and cytokine production caused by HTLV-1 infection.
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http://dx.doi.org/10.1016/j.biopha.2016.01.041DOI Listing
April 2016

Physalins B and F, seco-steroids isolated from Physalis angulata L., strongly inhibit proliferation, ultrastructure and infectivity of Trypanosoma cruzi.

Parasitology 2013 Dec 4;140(14):1811-21. Epub 2013 Sep 4.

Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, Rua Waldemar Falcão, 121, Candeal, Salvador, Bahia, CEP: 40296-710, Brazil.

We previously observed that physalins have immunomodulatory properties, as well as antileishmanial and antiplasmodial activities. Here, we investigated the anti-Trypanosoma cruzi activity of physalins B, D, F and G. We found that physalins B and F were the most potent compounds against trypomastigote and epimastigote forms of T. cruzi. Electron microscopy of trypomastigotes incubated with physalin B showed disruption of kinetoplast, alterations in Golgi apparatus and endoplasmic reticulum, followed by the formation of myelin-like figures, which were stained with MDC to confirm their autophagic vacuole identity. Physalin B-mediated alteration in Golgi apparatus was likely due to T. cruzi protease perturbation; however physalins did not inhibit activity of the trypanosomal protease cruzain. Flow cytometry examination showed that cell death is mainly caused by necrosis. Treatment with physalins reduced the invasion process, as well as intracellular parasite development in macrophage cell culture, with a potency similar to benznidazole. We observed that a combination of physalins and benznidazole has a greater anti-T. cruzi activity than when compounds were used alone. These results indicate that physalins, specifically B and F, are potent and selective trypanocidal agents. They cause structural alterations and induce autophagy, which ultimately lead to parasite cell death by a necrotic process.
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http://dx.doi.org/10.1017/S0031182013001297DOI Listing
December 2013

Physalin B inhibits Trypanosoma cruzi infection in the gut of Rhodnius prolixus by affecting the immune system and microbiota.

J Insect Physiol 2012 Dec 16;58(12):1620-5. Epub 2012 Oct 16.

Laboratório de Bioquímica e Fisiologia de Insetos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil.

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 1 mg/ml of blood meal (oral application), or 20 ng/insect (applied topically) or 57 ng/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.
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http://dx.doi.org/10.1016/j.jinsphys.2012.10.001DOI Listing
December 2012

Antimalarial activity of physalins B, D, F, and G.

J Nat Prod 2011 Oct 28;74(10):2269-72. Epub 2011 Sep 28.

Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.

The antimalarial activities of physalins B, D, F, and G (1-4), isolated from Physalis angulata, were investigated. In silico analysis using the similarity ensemble approach (SEA) database predicted the antimalarial activity of each of these compounds, which were shown using an in vitro assay against Plasmodium falciparum. However, treatment of P. berghei-infected mice with 3 increased parasitemia levels and mortality, whereas treatment with 2 was protective, causing a parasitemia reduction and a delay in mortality in P. berghei-infected mice. The exacerbation of in vivo infection by treatment with 3 is probably due to its potent immunosuppressive activity, which is not evident for 2.
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http://dx.doi.org/10.1021/np200260fDOI Listing
October 2011

Activity of physalins purified from Physalis angulata in in vitro and in vivo models of cutaneous leishmaniasis.

J Antimicrob Chemother 2009 Jul 19;64(1):84-7. Epub 2009 May 19.

Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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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http://dx.doi.org/10.1093/jac/dkp170DOI Listing
July 2009

Trypanosoma rangeli: effects of physalin B on the immune reactions of the infected larvae of Rhodnius prolixus.

Exp Parasitol 2006 Jan 3;112(1):37-43. Epub 2005 Nov 3.

Departamento de Bioquímica e Biologia Molecular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (Fiocruz), Av. Brazil 4365, Rio de Janeiro 21045-900, RJ, Brazil.

Physalins are seco-steroids obtained from plants of the family Solanaceae. Herein, we tested Physalis angulata L purified physalin B as an immunomodulatory compound in 5th-instar larvae of Rhodnius prolixus, which were systemically infected with the H14 Trypanosoma rangeli strain protozoan. In uninfected insects, the effective concentration of physalin B, which inhibited 50% of the blood ingested (ED(50)) volume, was 15.2+/-1.6 microg/ml of the meal. Ecdysis processes and mortality in uninfected larvae, treated orally with physalin B in concentrations ranging from 1 to 10 microg/ml, was similar to that observed in insects not treated with physalin B. However, R. prolixus larvae previously fed on blood containing 1.0, 0.1, and 0.01 microg of physalin B/ml exhibited mortality rates of 78.1, 54.3, and 12.7%, respectively, 6 days after inoculation of T. rangeli (1 x 10(3) parasites/insect), whereas only 7.2% mortality was observed in the control group, injected with sterile culture medium. The insects treated with physalin B (0.1 microg/ml) and inoculated with T. rangeli did not modify the phenoloxidase (PO) activity and total hemocyte count in the hemolymph. However, physalin B treatment caused a reduction in hemocyte micro-aggregation and nitric oxide production and enhanced the parasitemia in the hemolymph. These results demonstrate that physalin B from P. angulata is a potent immunomodulatory substance for the bloodsucking insect, R. prolixus.
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http://dx.doi.org/10.1016/j.exppara.2005.09.003DOI Listing
January 2006

Mechanisms of the anti-inflammatory effects of the natural secosteroids physalins in a model of intestinal ischaemia and reperfusion injury.

Br J Pharmacol 2005 Sep;146(2):244-51

Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627 - Pampulha, 31270-901 Belo Horizonte MG Brazil.

Reperfusion of an ischaemic tissue is associated with an intense inflammatory response and inflammation-mediated tissue injury. Physalins, a group of substances with secosteroidal chemical structure, are found in Physalis angulata stems and leaves. Here, we assessed the effects of physalins on the local, remote and systemic injuries following intestinal ischaemia and reperfusion (I/R) in mice and compared with the effects of dexamethasone. Following I/R injury, dexamethasone (10 mg kg(-1)) or physalin B or F markedly prevented neutrophil influx, the increase in vascular permeability in the intestine and the lungs. Maximal inhibition occurred at 20 mg kg(-1). Moreover, there was prevention of haemorrhage in the intestine of reperfused animals. Dexamethasone or physalins effectively suppressed the increase in tissue (intestine and lungs) and serum concentrations of TNF-alpha. Interestingly, treatment with the compounds was associated with enhancement of IL-10. The anti-inflammatory effects of dexamethasone or physalins were reversed by pretreatment with the corticoid receptor antagonist RU486 (25 mg kg(-1)). The drug compounds suppressed steady-state concentrations of corticosterone, but did not alter the reperfusion-associated increase in levels of corticosterone. The IL-10-enhancing effects of the drugs were not altered by RU486. In conclusion, the in vivo anti-inflammatory actions of physalins, natural steroidal compounds, appear to be mostly due to the activation of glucocorticoid receptors. Compounds derived from these natural secosteroids may represent novel therapeutic options for the treatment of inflammatory diseases.
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http://dx.doi.org/10.1038/sj.bjp.0706321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1576270PMC
September 2005

Relationship between the concentration of supplemental oxygen and signal intensity of CSF depicted by fluid-attenuated inversion recovery imaging.

AJNR Am J Neuroradiol 2003 Oct;24(9):1863-8

Section of Radiology, Santa Casa de Misericórdia de São Paulo, Brazil.

Background And Purpose: Prior reports have described increased signal intensity (SI) of CSF on fluid-attenuated inversion recovery (FLAIR) images of anesthetized patients receiving 100% O(2). This appearance can simulate that of diseases. We evaluated the relationship between the concentration of inhaled O(2) and the development of increased SI of CSF on FLAIR images.

Methods: FLAIR was performed in 25 healthy volunteers breathing room air and 100% O(2) through a face mask for 5, 10, and 15 minutes. MR imaging, including FLAIR imaging, was performed in 52 patients with no potential meningeal abnormalities under general anesthesia: 21 received an equal mixture of N(2)O and O(2), and 31 received 100% O(2). The SI of CSF in volunteers and patients was graded in several locations by using a three-point scale.

Results: SI of CSF significantly increased (P <.05) in various locations, in both volunteers and patients breathing 100% O(2), when compared with SI in the same volunteers breathing room air. Hyperintensity of CSF was not significantly different in volunteers receiving 100% O(2) through a face mask compared with anesthetized patients receiving 100% O(2) through a laryngeal airway or an endotracheal tube. No significant increase in SI occurred in patients receiving 50% O(2), when compared with the SI of volunteers breathing room air.

Conclusion: Supplemental oxygen at 100% is a main cause of artifactual CSF hyperintensity on FLAIR images, regardless of the anesthetic drug used. This artifact does not develop when 50% O(2) is administered.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976282PMC
October 2003

Inhibition of macrophage activation and lipopolysaccaride-induced death by seco-steroids purified from Physalis angulata L.

Eur J Pharmacol 2003 Jan;459(1):107-12

Centro de Pesquisas Gonçalo Moniz, Rua Waldemar Falcão, 121-Brotas-FIOCRUZ, 40295-001 BA, Salvador, Brazil. [email protected]

Physalis angulata L. is an annual herb widely used in popular medicine for the treatment of a variety of pathologies. Here, we tested immunomodulatory activities of physalins, seco-steroids purified from P. angulata extracts. Addition of physalins B, F or G, but not D, caused a reduction in nitric oxide production by macrophages stimulated with lipopolysaccaride and interferon-gamma. In the presence of physalin B, macrophages stimulated with lipopolysaccaride, alone or in combination with interferon-gamma, produced lower levels of tumour necrosis factor (TNF)-alpha, interleukin-6 and interleukin-12. The inhibitory activity of physalin B, unlike that of dexamethasone, was not reversed by RU486 [(4-dimethylamino) phenyl-17beta-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one], an antiglucocorticoid. Physalin B-treated mice had lower levels of serum TNF-alpha than control mice after lipopolysaccaride challenge. More importantly, mice injected with physalins B, F or G survived after a lethal lipopolysaccaride challenge. These results demonstrate that seco-steroids from P. angulata are potent immunomodulatory substances and act through a mechanism distinct from that of dexamethasone.
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http://dx.doi.org/10.1016/s0014-2999(02)02829-7DOI Listing
January 2003
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