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

Bezerra-Santos, C.R.; Vieira‐de‐Abreu, Adriana; Vieira, Giciane Carvalho; Filho, Jaime Ribeiro; Barbosa-Filho, José Maria; Pires, Ana Lucia A.; Martins, Marco A.; Souza, Heitor; Bandeira‐Melo, Christianne; Bozza, Patrı́cia T.; Piuvezam, Márcia Regina

doi:10.1016/j.intimp.2012.03.014

Cited by 40 publications

(16 citation statements)

References 24 publications

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“…Allergen-induced AHR has been associated with Th2dependent cytokines, such as IL-4, IL-5, IL-8, IL-13 and TNF-a, eosinophil infiltration into the lungs, mucus secretion (29,32), and production of collagen (29,42) and other ECM proteins (42,43). Changes of airway remodeling, which occur in response to persistent inflammation, correlate with the development of AHR (29,32).…”

Section: Hong Kim and Romentioning

confidence: 99%

Expression of Airway Remodeling Proteins in Mast Cell Activated by TGF-β Released in OVA-Induced Allergic Responses and Their Inhibition by Low-Dose Irradiation or 8-oxo-dG

Hong

Kim

2014

Radiation Research

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Allergic asthma is characterized by chronic airway remodeling, which is associated with the expression of extracellular matrix proteins (ECM) by TGF-β. However, to date there are no reports demonstrating that structural proteins are directly expressed in mast cells. This study aimed to investigate whether ECM proteins are expressed in mast cells activated with antigen/antibody reaction, and whether the resolution effects of irradiation or 8-oxo-dG may contribute to allergic asthma prevention. Bone marrow-derived mast cells (BMMCs) were activated with DNP-HSA/anti-DNP IgE antibody (act-BMMCs). C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) to induce allergic asthma. Mice were treated orally with 8-oxo-dG or exposed to whole body irradiation (using (137)Cs gamma ray at a dose of 0.5 Gy) for three consecutive days 24 h after OVA challenge. Expression of extracellular matrix (ECM) proteins, TGF-β signaling molecules and NF-κB/AP-1 was determined in the BMMCs, bronchoalveolar lavage (BAL) cells or lung tissues using Western blot, polymerase chain reaction (PCR) and electrophoretic mobility shift assay (EMSA), respectively. Act-BMMCs increased expression of ECM proteins, TGF-β/TGF-β receptor I, TGF-β signaling molecules and cytokines; and increased both NF-κB and AP-1 activity. In addition, the population of mast cells; expression of mast cell markers, TGF-β signaling molecules, ECM proteins/amounts; OVA-specific serum IgE level; numbers of goblet cells; airway hyperresponsiveness; cytokines/chemokines were increased in BAL cells and lung tissues of OVA-challenged mice. All of the above end points were reduced by irradiation or 8-oxo-dG in vitro and in vivo, respectively. The data suggest that mast cells induce expression of ECM proteins through TGF-β produced in inflammatory cells of OVA mice and that post treatment of irradiation or 8-oxo-dG after OVA-challenge may reduce airway remodeling through down-regulating mast cell re-activation by TGF-β/Smad signals.

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Section: Hong Kim and Romentioning

confidence: 99%

Expression of Airway Remodeling Proteins in Mast Cell Activated by TGF-β Released in OVA-Induced Allergic Responses and Their Inhibition by Low-Dose Irradiation or 8-oxo-dG

Hong

Kim

2014

Radiation Research

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“…The alkaloid warifteine, the main alkaloid isolated from this plant extract, was previously shown to inhibit leukotriene production, which would impart an anti-inflammatory effect to this alkaloid [7, 42]. In the present study we further characterized the anti-inflammatory mechanism of warifteine and described the effect of the alkaloid in neutrophil migration.…”

Section: Discussionmentioning

confidence: 58%

“…Peritoneal exudates were obtained between 3 and 5 h after casein injection since kinetic studies have shown that neutrophil migration would peak in this time interval (data not shown). The doses of warifteine used in vivo were the ones that were previously characterized as able to significantly inhibit allergic inflammation [7, 42] and to induce maximal inhibition of neutrophil migration in preliminary studies (data not shown). In order to thoroughly investigate the effect of warifteine in neutrophil migration in vivo , the inhibitory effect of warifteine in casein-induced in vivo neutrophil mobilization was analyzed and determined by three approaches: determination of the number of cells in the PMN gate by flow cytometry analysis in plots of forward scatter (FSC) by side scatter (SSC) (Figures 2(a) and 2(b)), calculation of the percentage of Gr-1+ cells in the PMN gate measured by flow cytometry (Figures 2(c) and 2(d)), and, finally, determination of the percentage of neutrophils in cytospin smears (Figure 2(e)).…”

Section: Resultsmentioning

confidence: 99%

Warifteine, an Alkaloid Purified fromCissampelos sympodialis, Inhibits Neutrophil MigrationIn VitroandIn Vivo

Lima

Rocha

Guimarães-Costa

et al. 2014

Journal of Immunology Research

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Cissampelos sympodialis Eichl is a plant from the Northeast and Southeast of Brazil. Its root infusion is popularly used for treatment of inflammatory and allergic diseases. We investigated whether warifteine, its main alkaloid, would have anti-inflammatory effect due to a blockage of neutrophil function. In vivo warifteine treatment inhibited casein-induced neutrophil migration to the peritoneal cavity but did not inhibit neutrophil mobilization from the bone marrow. Analysis of the direct effect of warifteine upon neutrophil adherence and migration in vitro demonstrated that the alkaloid decreased cell adhesion to P and E-selectin-transfected cells. In addition, fLMP-induced neutrophil migration in a transwell system was blocked by warifteine; this effect was mimicked by cAMP mimetic/inducing substances, and warifteine increased intracellular cAMP levels in neutrophils. The production of DNA extracellular traps (NETs) was also blocked by warifteine but there was no alteration on PMA-induced oxidative burst or LPS-stimulated TNFα secretion. Taken together, our data indicate that the alkaloid warifteine is a potent anti-inflammatory substance and that it has an effect on neutrophil migration through a decrease in both cell adhesion and migration.

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“…Warifteine is an alkaloid obtained from the plant Cissampelos sympodialis that has been reported to inhibit airway hyper-responsiveness, lung remodeling, and eosinophil infiltration in a mouse model of asthma (Bezerra-Santos et al, 2012).…”

Section: Alkaloidsmentioning

confidence: 99%

Nutraceuticals in Respiratory Disorders

Gulati¹,

Rai²,

Chaudhary³

et al. 2016

Nutraceuticals

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

Cited by 40 publications

References 24 publications

Expression of Airway Remodeling Proteins in Mast Cell Activated by TGF-β Released in OVA-Induced Allergic Responses and Their Inhibition by Low-Dose Irradiation or 8-oxo-dG

Expression of Airway Remodeling Proteins in Mast Cell Activated by TGF-β Released in OVA-Induced Allergic Responses and Their Inhibition by Low-Dose Irradiation or 8-oxo-dG

Warifteine, an Alkaloid Purified fromCissampelos sympodialis, Inhibits Neutrophil MigrationIn VitroandIn Vivo

Nutraceuticals in Respiratory Disorders

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