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DOI: 10.1055/s-0029-1186165
© Georg Thieme Verlag KG Stuttgart · New York
Inhibitory Effect of the Alkaloid Warifteine Purified from Cissampelos sympodialis on B Lymphocyte Function In Vitro and In Vivo
Publication History
received Dec. 5, 2008
revised July 17, 2009
accepted August 28, 2009
Publication Date:
28 September 2009 (online)
![](https://www.thieme-connect.de/media/plantamedica/201004/lookinside/thumbnails/10.1055-s-0029-1186165-1.jpg)
Abstract
The aqueous fraction of the ethanolic extract of the plant Cissampelos sympodialis (Menispermaceae) was previously described to inhibit B cell function. The alkaloid warifteine is the major component of this extract. In the present study we investigated the effect of warifteine on B lymphocyte function and characterized its mechanism of action. Purified splenic murine B lymphocytes were stimulated with either Toll-like receptor (TLR) ligands (LPS, Pam3Cys and CpG oligodeoxynucleotides) or anti-IgM antibody and the effect of warifteine on B cell response was investigated. Warifteine inhibited both the proliferative response and immunoglobulin (Ig) secretion induced by these stimuli. Kinetics studies demonstrated that warifteine blocked B cell function even when added after 24 h of a 72 h culture. The inhibitory effect of warifteine was also detected in cultures activated by phorbol myristate acetate and calcium ionophore. We investigated the signal transduction pathways blocked by warifteine. It did not modify the total protein phosphorylation pattern in LPS and anti-IgM-stimulated B cell cultures. It did, however, decrease the rise in intracellular calcium levels, the phosphorylation of the mitogen activated protein kinase (MAPK) ERK and the intranuclear levels of the transcription factor NFκB. Warifteine also induced an increase in cAMP and its effect on LPS-induced proliferation was mimicked by the control adenyl cyclase activator forskolin. In vivo Ig production induced by the TI-2 antigen TNP-ficoll was also inhibited by warifteine. Taking together, our data suggest that warifteine is a potent inhibitor of B cell response both in vitro and in vivo and that this effect may be due to the induction of increased intracellular cAMP levels, suggesting that this substance may be useful as a modulator of B cell function.
Key words
B lymphocyte - Cissampelos sympodialis - Menispermaceae - warifteine - immunoglobulin - signal transduction - Toll‐like receptors
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Dr. Ligia Peçanha
Departamento de Imunologia
Instituto de Microbiologia Prof. Paulo de Góes
Universidade Federal do Rio de Janeiro
CCS
Bloco I, sala I2-062
Ilha do Fundão
21944–570 Rio de Janeiro
Brazil
Phone: + 55 21 25 62 67 47
Fax: + 55 21 25 60 83 44
Email: lpecanha@micro.ufrj.br
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