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Alkaloids from Galipea longiflora Krause modify the maturation of human dendritic cells and their ability to stimulate allogeneic CD4+ T cells
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
(English)Article in journal (Refereed) Submitted
Abstract [en]

Alkaloids obtained from the plant Evanta have been shown to have dual effects in Leishmania infection; a direct leishmanicidal effect on the parasite and more importantly, the alkaloids affect both polyclonal and Leishmania-specific stimulation of T-cells.  

Dendritic cells (DCs) play a pivotal role in stimulation and polarization of naïve T cells towards a Th1, Th2, Th17 or regulatory phenotype. In leishmaniasis, the interactions between the parasites and DCs are complex and involve contradictory functions that can stimulate or suppress T cell responses, leading to the control of infection or progression of disease.

 In this study the effect of an alkaloid extract of Evanta (AEE) or the purified alkaloid 2-phenilquinoline (2Ph) on the activation of human DCs and their ability to stimulate allogeneic CD4+ T cells was analyzed. The expression of surface activation molecules was not affected on DCs stimulated in the presence of AEE or 2Ph nor did AEE-DCs or 2Ph-CDs affect the expression of activation surface molecules on allogeneic CD4+ T cells. In contrast, as compared with control, the secretion of IL-12p40, IL-23 and IL-6 was lower from AEE-DCs and 2Ph-CDs and allogeneic CD4+ T cells co-cultured with these DCs secreted lower levels of IFN-γ and IL-10 but the same levels of IL-17.

These results demonstrate that AEE and 2Ph affect the stimulation of DCs and their ability to stimulate allogeneic CD4+ T cells by reducing the production of IFN-g, IL-12 p40, IL-6 and IL-23. This suggests that AEE and 2Ph may take part in regulation of inflammation.

Keyword [en]
Leishmaniasis, Galipea longiflora Krause, natural products, dendritic cells, cytokines
National Category
Medical and Health Sciences
Research subject
Immunology
Identifiers
URN: urn:nbn:se:su:diva-81447OAI: oai:DiVA.org:su-81447DiVA: diva2:561733
Available from: 2012-10-21 Created: 2012-10-21 Last updated: 2012-10-22Bibliographically 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)
Opponent
Supervisors
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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