| 1. |
- Calla-Magariños, Jacqueline, 1963-, et al.
(author)
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An alkaloid extract of Evanta, traditionally used as anti-Leishmania agent in Bolivia, inhibits cellular proliferation and interferon-g production in polyclonally activated cells
- 2009
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In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 69:3, s. 251-258
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Journal article (peer-reviewed)abstract
- Traditional medicine and scientific studies have shown that the raw extract ofEvanta [Galipea longiflora, Angostura longiflora (Krause) Kallunki] exhibits antileishmanialactivity. We hypothesized that the healing observed when usingthis plant might not only be due to the direct action on the parasite, but possiblyto a parallel effect on the host immune response to the parasite involvedin the healing process. We show here that an alkaloid extract of Evanta (AEE)directly killed the parasite already at a dose of 10 lg ⁄ ml, but at this low concentration,AEE did not have a major effect on viability and proliferation ofeukaryotic cells. The whole extract was also found to be stronger than 2-phenylquinoline,the most prominent alkaloid in AEE. AEE was not directlystimulating B or T cells or J774 macrophages. However, it interfered with theactivation of both mouse and human T cells, as revealed by a reduction of invitro cellular proliferation and interferon-gamma (IFN-c) production. The effectwas more evident when the cells were pretreated with AEE and subsequentlystimulated with the polyclonal T-cell activators Concanavalin A and anti-CD3.Taken together, our results suggest that Evanta have a direct leishmanicidaleffect and due to the effect on IFN-c production it might contribute to controlthe chronic inflammatory reaction that characterize Leishmania infectionpathology, but in vivo studies are necessary to corroborate this finding.
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| 2. |
- Fernández Mastache, Elena, et al.
(author)
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Somatic hypermutation of Ig genes is affected differently by failures in apoptosis caused by disruption of Fas (lpr mutation) or by over-expression of Bcl-2
- 2006
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In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 63:6, s. 420-429
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Journal article (peer-reviewed)abstract
- The effects of the two main apoptotic pathways on the somatic hypermutation process were analysed. Transgenic mice carrying the V(kappa)Ox1-J(kappa)5 rat transgene were crossed with Fas-deficient lpr mice or with mice overexpressing the Bcl-2 protein. The transgenic V(kappa)Ox1 segment and the endogenous J(H)4-C-mu Ig intron from Peyer's patches germinal centre B cells were sequenced to study the intrinsic somatic hypermutation process without the skewing effects of specific antigen selection. The lpr/ox mice displayed, in both regions, a high level of mutations with a normal pattern of substitutions. On the contrary, the bcl-2/ox mice displayed a lower level of mutations with an altered pattern, showing a decreased mutational rate in the intrinsic hotspots of the V(kappa)Ox1 gene. Our results suggest that the lpr mutation does not have a direct effect on the somatic hypermutation process, but rather on the negative selection of B cells in the germinal centres, leading to the accumulation of recurrent mutations. In contrast, Bcl-2 overexpression might influence the somatic hypermutational process either by altering the incorporation of mutations or by enhancing the repair mechanism(s). The present work supports the hypothesis that both apoptotic pathways, Fas and Bcl-2, play distinct roles in the germinal centre reactions.
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| 3. |
- Calla-Magariños, Jacqueline, et al.
(author)
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Quinolinic Alkaloids from Galipea longiflora Krause Suppress Production of Proinflammatory Cytokines in vitro and Control Inflammation in vivo upon Leishmania Infection in Mice
- 2013
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In: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 77:1, s. 30-38
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Journal article (peer-reviewed)abstract
- An antileishmanial activity of quinolinic alkaloids from Galipea longiflora Krause, known as Evanta, has been demonstrated. We have previously shown that, apart from its leishmanicidal effect, in vitro pretreatment of spleen cells with an alkaloid extract of Evanta (AEE) interfered with the proliferation and interferon-γ production in lymphocytes polyclonally activated either with concanavalin A or anti-CD3. In the present study, we investigated if AEE could interfere with antigen-specific lymphocyte activation. We found that in vitro and in vivo treatment reduced recall lymphocyte responses, as measured by IFN-γ production (55% and 63% reduction compared to untreated cells, respectively). Apart from IFN-γ, the production of IL-12 and TNF was also suppressed. No effects were observed for meglumine antimoniate (SbV), the conventional drug used to treat leishmaniasis. When mice infected with Leishmania braziliensis promastigotes in the hind footpad were treated with AEE, the dynamics of the infection changed and the footpath thickness was efficiently controlled. The parasite load was also reduced but to a lesser extent than upon treatment with SbV. Combined treatment efficiently controlled both the thickness and parasite load as smaller lesions during the entire course of the infection were seen in the mice treated with AEE plus SbV compared with AEE or SbV alone. We discuss the benefits of combined administration of AEE plus SbV.
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| 4. |
- Calla-Magariños, Jacqueline, 1963-, et al.
(author)
-
Quinolinic alkaloids from Galipea longiflora suppress inflammatory cytokine production in vitro and control inflammatory reaction in vivo upon Leishmania infection
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In: Scandinavian Journal of Immunology. - 0300-9475 .- 1365-3083.
-
Journal article (peer-reviewed)abstract
- An antileishmanial activity of quinolinic alkaloids from Galipea longiflora Krause, known as Evanta, has been demonstrated. We have previously shown that, apart from its leishmanicidal effect, in vitro pretreatment of spleen cells with an alkaloid extract of Evanta (AEE) interfered with the proliferation and interferon-g production in lymphocytes polyclonally activated either with concanavalin A or anti-CD3. In the present study, we investigated if AEE could interfere with antigen-specific lymphocyte activation. We found that in vitro and in vivo treatment reduced recall lymphocyte responses, as measured by IFN-g production (55 % and 63 % reduction compared to untreated cells, respectively). Apart from IFN-g, the production of IL-12 and TNF were also suppressed. No effects were observed for meglumine antimoniate (SbV), the conventional drug used to treat leishmaniasis. When mice infected with Leishmania braziliensis promastigotes in the hind footpad were treated with AEE, the dynamics of the infection changed and the footpath thickness was efficiently controlled. The parasite load was also reduced but to a lesser extent than upon treatment with SbV. Combined treatment efficiently controlled both the thickness and parasite load since smaller lesions during the entire course of the infection were seen in the mice treated with AEE plus SbV compared with AEE or SbV alone. We discuss the benefits of combined administration of AEE plus SbV.
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