Tablet of Spondias mombin L. Developed from Nebulized Extract Prevents Gastric Ulcers in Mice via Cytoprotective and Antisecretory Effects

Abstract

Spondias mombin L. (Anacardiaceae) has a worldwide distribution and is present in all regions of Brazil. Its leaves, flowers and bark are used as teas in folk medicine to treat diseases of the digestive system. This study aimed to evaluate the acute non-clinical toxicity, gastroprotective activity, and the related mechanisms of action of nebulized extract and tablets based on dried Spondias mombin (SmNE). SmNE screening showed the presence of flavonoids (0.65%), polyphenols (25.50%), where the major compound is gallic acid. In the acute oral toxicity assay, a dose of 2000 mg/kg of SmNE administered orally in Swiss mice did not induce any behavioral changes. SmNE (250 or 500 mg/kg p.o) significantly reduced the ulcerative lesion area when compared to the control group in ethanol and non-steroidal anti-inflammatory drug (NSAIDs) models. Results showed that treatment with SmNE (250 mg/kg) reduced acid secretion and gastric content, accompanied with an increase in pH. Previous administration of indomethacin and glibenclamide reversed the protection provided by SmNE, confirming the participation of prostaglandins (PGs) and ATP-sensitive potassium channels (KATP) in its gastroprotective effect. The SmNE tablets met the pharmacopeial quality requirements with gastroprotective activity and similar protection in comparison to the isolated extract administrated. In conclusion, SmNe has a gastroprotective activity related to cytoprotective mechanisms, such as the participation of endogenous prostaglandins and KATP channels, having an anti-secretory effect with systemic action. The formulation obtained presented gastroprotective effects similar to the administration of the extract, the tablets showed favorable compression characteristics by the direct route and met the pharmacopeial quality requirements.

Keywords: Spondias mombin; cytoprotection; gastric ulcer; herbal medicine.

Figure 1

HPLC chromatogram of the nebulized leaf extract of Spondias mombin. 1. gallic acid (7 min).

Figure 2

Effect of oral pretreatment with SmNE in the ethanol-induced ulcer model. SmNE administered in doses of 250 and 500 mg/kg p.o, lansoprazole 30 mg/kg. The results are expressed as the mean ± SEM (group). One-way analysis of variance (ANOVA), followed by Dunnett’s multiple comparison test. *** (p ˂ 0.001), versus negative control n = 6 animals.

Figure 3

Effect of oral pretreatment with SmNE on the non-steroidal anti-inflammatory drug (NSAID)-induced ulcer model. SmNE administered at a dose of 250 mg/kg p.o, cimetidine 100 mg/kg. The results are expressed as the mean ± SEM (group). One-way analysis of variance (ANOVA), followed by Dunnett’s multiple comparison test. *** (p < 0.001) versus negative control n = 6 animals.

Figure 4

Oral pretreatment effect with SmNE in the ethanol-induced ulcer model, with pretreatment with indomethacin (10 mg/kg). SmNE at a dose of (250 mg/kg), misoprostol (50 µg/kg). The results are expressed as the mean ± SEM (group). One-way analysis of variance (ANOVA), followed by Tukey’s multiple comparison test. * (p < 0.05), ** (p < 0.01) versus negative control n = 6 animals. Saline, SmNE, and misoprostol groups pretreated with saline versus pretreatment with indomethacin * (p ˂ 0.05), ** (p < 0.01). n = 6 animals. n.s—means not significant.

Figure 5

Effect of oral pretreatment with SmNE in the ethanol-induced ulcer model and pretreatment with glibenclamide (10 mg/kg). SmNE at a dose of (250 mg/kg). The results are expressed as the mean ± SEM (group). One-way analysis of variance (ANOVA), followed by Tukey’s multiple comparison test. * (p < 0.05), *** (p < 0.01). Saline and SmNE groups pretreated with saline versus pretreatment with glibenclamide * (p < 0.05), ** (p ˂ 0.01), *** (p < 0.001). n = 6 animals.

Figure 6

Image of tablets.

Figure 7

Average tablet weight.

Figure 8

Effect of oral pretreatment with the SmNE tablet on the ethanol-induced ulcer model. SmNE tablet 800 mg/kg p.o, lansoprazole 30 mg/kg, and excipients 550 mg/kg. The results are expressed as the mean ± SEM (group). One-way analysis of variance (ANOVA), followed by Dunnett’s multiple comparison test. *** (p < 0.001) versus negative control n = 6 animals.