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. 2020 Dec 23:11:572574.
doi: 10.3389/fphar.2020.572574. eCollection 2020.

Oceanapia magna Sponge Presents Dual Effect on the Gastrointestinal Motility of Rodents: In Vitro and In Vivo Assays

Affiliations

Oceanapia magna Sponge Presents Dual Effect on the Gastrointestinal Motility of Rodents: In Vitro and In Vivo Assays

Joedna Cavalcante Pereira et al. Front Pharmacol. .

Abstract

Oceanapia magna Santos-Neto, Nascimento, Cavalcanti and Pinheiro sponges are distributed across tropical worldwide seas. Some studies of marine products have shown interesting activities in smooth muscle models. Hence, we assessed the effect of the ethanolic extract of Oceanapia magna. (OC-EtOH) on acute toxicity and gastrointestinal motility (in vitro and in vivo) in rodent models. On guinea pig ileum, OC-EtOH induced a concentration dependent contraction on basal tonus, which was not inhibited by atropine, but in the presence of pyrilamine or verapamil, the effect was antagonized. Contrastingly, on KCl- or histamine-induced contractions, OC-EtOH presented a transient contraction followed by a concentration-dependent relaxation. Moreover, OC-EtOH presented a relaxant profile on cumulative curves to CaCl2 and tonic contraction induced by S-(-)-BayK8644, through Cav blockade. The acute toxicity assay showed that OC-EtOH (2,000 mg/kg, p.o.) did not present any sign of toxicity in female mice. Additionally, OC-EtOH presented antidiarrheal effect in mice, increased the intestinal normal transit and reduced the castor oil-induced intestinal transit. Thus, OC-EtOH presented a dual effect on guinea pig ileum promoting contraction through activation of H1 and CaV, and relaxation through CaV blockade, besides the effect on upper gastrointestinal transit in mice, showing a potential medicinal use of this sponge in intestinal diseases such as diarrhea.

Keywords: Oceanapia magna; intestinal transit; marine sponge; spasmogenic; spasmolytic.

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Figures

FIGURE 1
FIGURE 1
Chromatogram (HPLC-ELSD) of Oceanapia magna fraction.
FIGURE 2
FIGURE 2
Representative record of OC-EtOH (0.1–2,187 μg/ml, n = 5) cumulative contractile effect on basal tonus of guinea pig ileum (A). Cumulative concentration-response curves to OC-EtOH (● on basal tonus of guinea pig ileum (n = 5) (B). The upward arrows represent the concentration of 0.1; 0.3; 1; 3; 9; 27; 81; 243; 729 and 2,187 μg/ml of OC-EtOH. W, wash.
FIGURE 3
FIGURE 3
Cumulative concentration–response curves to OC-EtOH (A,C), CCh (B) and histamine (D) on guinea pig ileum in both absence (○, ●, ◀, ●) and presence of atropine 10–9 (▲), 3 × 10–9 (△), 10–8 (◆, ▼) and 3 × 10–8 M (◇, ▽) or pyrilamine 10–9 (green unfiled circle, orange unfiled circle), 3 × 10–9 (green filed square, orange filed square), 10–8 (green unfiled square, orange unfiled square), 3 × 10–8 (green filed triangle, orange filed triangle), 10–7 (green unfiled triangle, orange unfiled triangle) and 3 × 10–7 M (green filed diamond, orange filed diamond) on guinea pig ileum. Symbols and vertical bars represent the mean and S.E.M., respectively (n = 5). CCh = Carbachol. One-way ANOVA followed by Bonferroni’s post-test: ***p < 0.001 (control vs. pyrilamine).
FIGURE 4
FIGURE 4
Cumulative concentration–response curves to OC-EtOH in absence (●) and presence of verapamil 10–7 (), 3 × 10–7 (▲) and 10–6 () on guinea pig ileum. Symbols and vertical bars represent the mean and S.E.M., respectively (n = 5). One-way ANOVA followed by Bonferroni's post-test: ***p < 0.001 (control vs. verapamil).
FIGURE 5
FIGURE 5
Representative records of OC-EtOH relaxant effect on guinea pig ileum pre-contracted by KCl 40 mM (A), histamine 10–6 (B) or CCh 10–5 M (C) (n = 5).
FIGURE 6
FIGURE 6
OC-EtOH contractile effect under KCl-(A) and histamine-(B) induced tonic contractions on guinea pig ileum. Vertical bars represent the means and S.E.M., respectively. One-way ANOVA followed by Bonferroni’s post-test, significant differences are indicated by ***p < 0.001 (n = 5).
FIGURE 7
FIGURE 7
Effect of OC-EtOH on guinea pig ileum pre-contracted with KCl 40 mM (✖), histamine 10–6 M (□) or CCh 10–5 M (■) (n = 5). Symbols and vertical bars represent the mean and S.E.M., respectively.
FIGURE 8
FIGURE 8
Representative records of OC-EtOH relaxant effect on guinea pig ileum pre-contracted with KCl 40 mM in absence (A) and presence (B) of pyrilamine (n = 5). Pyri, pyrilamine.
FIGURE 9
FIGURE 9
Relaxant effect of OC-EtOH on guinea pig ileum pre-contracted with KCl 40 mM in absence (black cross) and presence (blue cross) of pyrilamine. Symbols and vertical bars represent the mean and S.E.M., respectively (n = 5). One-way ANOVA followed by Bonferroni’s post-test: *p < 0.05 (KCl vs. pyrilamine + KCl).
FIGURE 10
FIGURE 10
Cumulative concentration–response curves to CaCl2 in depolarizing medium nominally without Ca2+ in absence () and presence of 27 (blue filed circle), 81 (blue unfiled circle), 243 (blue filed triangle) and 729 μg/ml (blue unfiled triangle) of OC-EtOH (A) and in presence of 3 × 10–8 (red filed circle), 10–7 (red unfiled circle), 3 × 10–7 (red unfiled triangle10–6 (red filed triangle) and 3 × 10–6 M (red inverted filed triangle) of verapamil (B) on guinea pig ileum. Symbols and vertical bars represent the mean and S.E.M., respectively (n = 5). One-way ANOVA followed by Bonferroni's post-test: *p < 0.05 (control vs. verapamil or OC-EtOH).
FIGURE 11
FIGURE 11
Relaxant effect of OC-EtOH (A) on guinea pig ileum pre-contracted with KCl 40 mM (violet unfiled circle) and S-(-)-Bay K8644 3 × 10–7 M (violet right-pointing triangle) in pyrilamine presence and relaxant effect of verapamil (B) on guinea pig ileum pre-contracted with KCl 40 mM (black right-pointing triangle) and S-(-)-Bay K8644 3 × 10–7 M (violet filed square) in pyrilamine presence. Symbols and vertical bars represent the mean and S.E.M., respectively (n = 5). One-way ANOVA followed by Bonferroni's post-test: ***p < 0.001 (S-(-)-Bay K8644 vs. KCl).
FIGURE 12
FIGURE 12
Effect of OC-EtOH on normal (A) and castor-oil-induced (B) upper gastrointestinal transit in mice (n = 6). Columns and vertical bars represent the mean and S.E.M., respectively. One-way ANOVA followed by Bonferroni’s post-test: *p < 0.05 and ***p < 0.001 (saline vs. atropine/OC-EtOH).
FIGURE 13
FIGURE 13
Antidiarrheal effect of OC-EtOH on castor-oil-induced diarrhea in mice (n = 6). Percentage of total stools number (A) and percentage of liquid stools (B). Columns and vertical bars represent mean and S.E.M., respectively. One-way ANOVA followed by Bonferroni’s post-test: ***p < 0.001 (saline vs. loperamide/OC-EtOH).

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