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Quinolinic alkaloids from Galipea longiflora suppress inflammatory cytokine production in vitro and control inflammatory reaction in vivo upon Leishmania infection
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
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(English)In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083Article in journal (Refereed) Accepted
Abstract [en]

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.

Keyword [en]
Leishmania infection, Galipea longiflora Krause, Evanta, herbal medicine, cytokines, IFN-gamma, inflammation, meglumine antimoniate
National Category
Medical and Health Sciences
Research subject
Immunology
Identifiers
URN: urn:nbn:se:su:diva-81446OAI: oai:DiVA.org:su-81446DiVA: diva2:561730
Available from: 2012-10-21 Created: 2012-10-21 Last updated: 2017-12-07Bibliographically approved
In thesis
1. Bioactive leishmanicidal alkaloid molecules from Galipea longiflora Krause with immunomodulatory activity
Open this publication in new window or tab >>Bioactive leishmanicidal alkaloid molecules from Galipea longiflora Krause with immunomodulatory activity
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

According to WHO, leishmaniasis is endemic in 98 countries, and has been placed ninth in a global analysis of infectious diseases. Treatment of leishmaniasis is based on pentavalent antimonials but toxicity and developing resistance have been reported. Traditional medicine and scientific studies have shown that the extract of Galipea longiflora Krause (Evanta) exhibits antileishmanial activity. We hypothesized that the healing observed when using this plant might not only be due to the direct action on the parasite, but possibly to a parallel effect on the host immune response. We found that an alkaloid extract of Evanta (AEE) inhibited the growth of Leishmania braziliensis promastigotes while viability of eukaryotic cells was practically not affected. We also found that AEE interfered with polyclonal activation or Leishmania-specific re-stimulation of lymphocytes, as revealed by a reduction of in vitro cellular proliferation and IFN-g production. More important, AEE treatment of mice hosting L. braziliensis showed that AEE is able to control both inflammation and parasite load. Additionally, the healing process was improved when AEE and meglumine antimoniate were administered simultaneously. Dendritic cells (DCs) play a pivotal role in T-cell stimulation and polarization of naïve T cells. Therefore, we investigated if AEE could alter the activation of DCs and if allostimulatory DCs properties were altered if activated in the presence of AEE. DCs activated in the presence of AEE reduced the production of IL-12p40 and IL-23. When we analyzed the allostimulatory capacity of AEE-treated DCs, we found that allogeneic CD4+ T-cells secreted lower levels of IFN-γ.

In conclusion, this thesis provides valuable insight into the effects of Evanta derived extract. The dual effect found for AEE, on Leishmania parasite and on the immune response, suggests that AEE may be useful in controlling the parasite burden and preventing over-production of inflammatory mediators and subsequently avoiding tissue damage.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2012. 75 p.
Keyword
Leishmania infection, Leishmaniasis, herbal medicine, natural products, Galipea longiflora Krause, Evanta, cytokines, IFN-gamma, dendritic cells, inflammation, meglumine antimoniate
National Category
Medical and Health Sciences
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-81439 (URN)978-91-7447-586-9 (ISBN)
Public defence
2012-11-22, William-Olssonsalen, Geovetenskapens hus, Svante Arrhenius väg 14, Stockholm, 10:00 (English)
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Note

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Accepted. Paper 3: Submitted.

Available from: 2012-10-31 Created: 2012-10-20 Last updated: 2012-10-24Bibliographically approved

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