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Involvement of Potassium Channels, Nitric Oxide Synthase, and Guanylate Cyclase in the Spasmolytic Effect of Simaba ferruginea A.St.-Hil on Rat Isolated Ileum

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Abstract

Background and Aim

Simaba ferruginea A.St.-Hil. Popularly known as “calunga,” is a typical Brazilian cerrado plant whose rhizomes are popular for treating diarrhea.

Aims

The aim of this study was to evaluate the spasmolytic activity and the antidiarrheal effect of the ethanolic extract obtained from S. ferruginea (Sf-EtOH).

Methods

Ileal segments (1–2 cm) from male Wistar rats were mounted in isolated organ baths and connected to a force transducer, and then to an amplifier which was connected to a computer (AVS Projetos/São Paulo-SP). After stabilization for 60 min, under tension (1 gf), two submaximal contractions were induced with KCl 40 mM or carbachol 10−6 M on ileal segments. During the third tonic and sustained contraction, Sf-EtOH was added in cumulative concentrations to the organ bath. Incubations with L-NAME (10−4 M), ODQ (10−5 M), TEA+ (5 or 1 mM), glibenclamide (10−5 M), or apamine (100 nM) were prepared (n = 5), separately and used to verify the involvement of the nitric oxide synthase, guanylate cyclase, and potassium channels in the relaxing effect. The results were expressed as mean ± standard error of the mean and were statistically evaluated using one-way ANOVA followed by Bonferroni test, when necessary *p < 0.05.

Results

Sf-EtOH promotes relaxation on rat isolated ileum pre-contracted with CCh and KCl in a concentration-dependent manner. Sf-EtOH also inhibited ileum contractions against cumulative concentrations of carbachol (CCh), KCl, and CaCl2, shifting the curves to the right in a non-parallel manner with an Emax reduction. In the presence of potassium channel blockers, Sf-EtOH shifted the curves to the right with a reduction of Emax, suggesting the involvement of BKCa, KATP, and SKCa in its spasmolytic effect. In the presence of L-NAME or ODQ, the relaxation curves were shifted to the right, suggesting the involvement of this pathway in Sf-EtOH spasmolytic effect.

Conclusions

Sf-EtOH acts in a concentration-dependent manner, involving the positive modulation of K+ channels and NO pathway.

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Acknowledgments

We are thankful to the UFPI (Federal University of Piauı, Brazil), CNPq (Conselho Nacional de Desenvolvimento Cientıfico e Tecnológico, Brazil), CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nıvel Superior, Brazil) for the scholarships and Boris Timah Acha for reviewing the English language.

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Correspondence to Rita de Cássia M. Oliveira.

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Almendra, R.B., da Fonseca, O.C., Nunes, D.B. et al. Involvement of Potassium Channels, Nitric Oxide Synthase, and Guanylate Cyclase in the Spasmolytic Effect of Simaba ferruginea A.St.-Hil on Rat Isolated Ileum. Dig Dis Sci 64, 3104–3114 (2019). https://doi.org/10.1007/s10620-019-05667-7

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