Avaliação da atividade antiulcerogênica, antimicrobiana e citotóxica da cumarina escopoletina

Abstract

Scopoletin is a coumarin isolated from various species of Simaroubaceae family, among which is Simaba ferruginea (CECHINEL, unpublished data). Several studies have related among others, anti-inflammatory, antioxidant, antiulcer, anti-HIV activities for scopoletin. The objective of this study was to evaluate the antiulcer, antimicrobial and cytotoxic activities of scopoletin, using in vivo and in vitro experimental models. Dichloromethane fraction obtained from liquid-liquid partition of methanol extract of Simaba ferruginea, was subjected to column chromatography proceeding with monitoring the fractions by thin layer chromatography, and identification of coumarins such as scopoletin. For antiulcer activity assays, experimental gastric lesion models of ethanol in Swiss mice, and indomethacin in Wistar rats were employed. Scopoletin demonstrated antiulcerogenic activity only in the ethanol induced ulcer. The antiulcerogenic effect of scopoletin is due to its effective inhibition of the pro-inflammatory cytokines TNF-α and IL-1β but it had no effect on NO production in the in vitro assay conducted with cultured RAW 264.7 cells and no significant in vitro antioxidant activity against NO free radical scavenging. In the evaluation of antioxidant activity in vivo against MPO, CAT and GSH in mice ulcerated by ethanol, the antiulcer activity of scopoletin was independent of their actions on the enzymes GSH and MPO, but shown to be linked to its activity in the CAT, indicating the involvement of antioxidant mechanism in their gastroprotective effects. Anti-Helicobacter pylori (ATCC strains) tests were carried out using disk diffusion and broth microdilution. However, scopoletin was inactive in both tests. For the experiments anti-Helicobacter pylori (ATCC strains) tests were used for disk diffusion and broth microdilution. The scopoletin showed no antimicrobial activity in any of the two tests. Antimicrobial activity performed with 9 strains of bacteria and 5 strains of yeast did not demonstrate any anti-bacterial and antifungal activities. In cytotoxicity assays by Alamar blue test and micronucleus test for genotoxicity, the scopoletin showed no cytotoxicity in vitro. The results confirm the antiulcer activity of scopoletin and show its effect on pro-inflammatory cytokines and their antioxidant activity. Its absence of cytotoxicity and mutagenicity to confirm phytotherapeutical as a potential treatment of gastric ulcers.