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. 2020 Aug:85:106616.
doi: 10.1016/j.intimp.2020.106616. Epub 2020 May 22.

Warifteine and methylwarifteine inhibited the type 2 immune response on combined allergic rhinitis and asthma syndrome (CARAS) experimental model through NF-кB pathway

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Warifteine and methylwarifteine inhibited the type 2 immune response on combined allergic rhinitis and asthma syndrome (CARAS) experimental model through NF-кB pathway

Raquel F P Cavalcanti et al. Int Immunopharmacol. 2020 Aug.

Abstract

CARAS is an airway inflammation of allergic individuals, with a type 2 immune response. The pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study evaluated the alkaloids warifteine (War) and methylwarifteine (Mwar) from Cissampelos sympodialis in CARAS experimental model. Therefore, BALB/c mice were ovalbumin (OVA) sensitized and challenged and treated with both alkaloids. Treated animals showed a decrease (p < 0.05) of allergic signs as sneezing and nasal rubbings, histamine nasal hyperreactivity, and inflammatory cell migration into the nasal (NALF) and the bronchoalveolar (BALF) fluids, main eosinophils. In the systemic context, only Mwar reduced eosinophilia, however, both alkaloids reduced the serum levels of OVA-specific IgE. Histological analysis revealed that the alkaloids decreased the inflammatory cells into the subepithelial and perivascular regions of nasal tissue and the peribronchiolar and perivascular regions of lung tissue. Hyperplasia/hypertrophy of nasal and lung goblet cells were reduced in alkaloid treated animals; however, the treatment did not change the number of mast cells. The lung hyperactivity was attenuated by reducing hyperplasia of fibroblast and collagen fiber deposition and hypertrophy of the lung smooth muscle layer. The immunomodulatory effect was by decreasing of type 2 and 3 cytokines (IL-4/IL-13/IL-5 and IL-17A) dependent by the increasing of type 1 cytokine (IFN-γ) into the BALF of treated sick animals. Indeed, both alkaloids reduced the NF-кB (p65) activation on granulocytes and lymphocytes, indicating that the alkaloids shut down the intracellular transduction signals underlie the transcription of TH2 cytokine gens.

Keywords: Alkaloids; Allergy; Cissampelos sympodialis; Immunomodulatory effect; Transcription factor.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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