Inhibitory effect of the alkaloid warifteine purified from Cissampelos sympodialis on B lymphocyte function in vitro and in vivo.

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, Pam (3)Cys 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 NFkappaB. 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.

Rocha JD ，Decoté-Ricardo D ，Redner P ，Lopes UG ，Barbosa-Filho JM ，Piuvezam MR ，Arruda LB ，Maria Torres Peçanha L ... -  《-》

Anti-allergic properties of Cissampelos sympodialis and its isolated alkaloid warifteine.

Bezerra-Santos CR ，Vieira-de-Abreu A ，Barbosa-Filho JM ，Bandeira-Melo C ，Piuvezam MR ，Bozza PT ... -  《INTERNATIONAL IMMUNOPHARMACOLOGY》

Warifteine, an alkaloid purified from Cissampelos sympodialis, inhibits neutrophil migration in vitro and in vivo.

Lima TF ，Rocha JD ，Guimarães-Costa AB ，Barbosa-Filho JM ，Decoté-Ricardo D ，Saraiva EM ，Arruda LB ，Piuvezam MR ，Peçanha LM ... -  《-》

Effectiveness of Cissampelos sympodialis and its isolated alkaloid warifteine in airway hyperreactivity and lung remodeling in a mouse model of asthma.

Cissampelos sympodialis Eichl. (Menispermaceae) is a plant found in Northeastern and Southeast of Brazil and hot water infusion of C. sympodialis root bark is largely used in the indigenous and folk medicine to treat several inflammatory disorders, including asthma. Asthma is a chronic inflammatory allergic disease characterized by airway hyperreactivity (AHR), eosinophil tissue infiltration and lung remodeling. The aim of this study was to evaluate the therapeutic effect of C. sympodialis and its isolated alkaloid warifteine on allergen triggered airway hyperreactivity (AHR) and lung remodeling in murine model of asthma. The oral pre-treatment with C. sympodialis or warifteine inhibited allergen-induced AHR to inhaled methacholine and IL-13 levels in the bronchoalveolar lavage (BAL). In order to investigate the therapeutic potential of C. sympodialis and warifteine, animals were treated 1h after the last ovalbumin (OVA) challenge in sensitized animals. Similarly to the pre-treatment, post-treatment with warifteine was effective to inhibit significantly AHR to inhaled methacholine and to reduce IL-13 levels in the BAL. In addition, oral pre- or post-treatments with C. sympodialis or warifteine reduced OVA-induced eosinophil tissue infiltration, mucus production and subepithelial fibrosis to values similar to nonallergic controls. Our data show the anti-allergic and immunoregulatory properties of C. sympodialis, acting mostly through the active compound warifteine, to inhibit the airway hyperreactivity and lung remodeling through a mechanism at least partially dependent of IL-13 and eosinophil inhibition. Therefore placing warifteine as an interesting therapeutic candidate in allergic inflammation and corroborating the folk medicine use of C. sympodialis as anti-allergic plant.

Bezerra-Santos CR ，Vieira-de-Abreu A ，Vieira GC ，Filho JR ，Barbosa-Filho JM ，Pires AL ，Martins MA ，Souza HS ，Bandeira-Melo C ，Bozza PT ，Piuvezam MR ... -  《-》

A G protein-associated ERK pathway is involved in LPS-induced proliferation and a PTK-associated p38 MAPK pathway is involved in LPS-induced differentiation in resting B cells.

Kim J ，Yang HY ，Jang YS 《MOLECULAR IMMUNOLOGY》