ABSTRACT
Abstract The cytotoxicity and genotoxicity of the stilbenes (E)-methyl-4-(3-5-dimethoxystyryl)benzoate (ester), (E)-4-(3-5-dimethoxystyryl)aniline (amino), (Z)-1,3-dimethoxy-5-(4-methoxystyryl)benzene (cis-TMS) and (E)-1,3-dimethoxy-5-(4-methoxystyryl)benzene (trans-TMS) were investigated in this work. Structural modifications of resveratrol, a naturally occurring stilbene, have been previously performed, including the replacement of hydroxyl by different functional groups. Such modifications resulted in significant improvement of target-specific effects on cell death and antiproliferative responses. The parameters were evaluated using XTT assay, clonogenic survival assay and the cytokinesis-block micronucleus assay in CHO-K1 and HepG2 cell lines. The results showed that cis-TMS is approximately 250-fold more cytotoxic than the amino and ester, and 128-fold more cytotoxic than trans-TMS. When genotoxicity was evaluated, only the trans-TMS did not significantly increase the frequency of micronucleus (MN). While the cis-TMS induced a mean of 5.2 and 5.9 MN/100 cells at 0.5 μM in CHO-K1 and HepG2, respectively, the amino and ester induced 3.1 and 3.6 MN/100 cells at 10 μM in CHO-K1, respectively, and 3.5 and 3.8 in HepG2. Trans-TMS is genotoxic only in HepG2 cells. Based on these results, the cis-TMS was the most cytotoxic and genotoxic compound in both cell lines.
ABSTRACT
AbstractGastric ulcer is a prevalent gastrointestinal disease, and the drugs currently used in the treatment produce several adverse effects. In this context, the search for new therapeutic antiulcer agents is essential, and medicinal plants have great potential. Here, we investigated the gastroprotective properties of Copaifera langsdorffii Desf., Fabaceae, hydroalcoholic extract obtained from leaves and its isolated compounds. The phytochemistry studies and the compounds isolations were performed using chromatographic and spectroscopic methodologies. The hydroalcoholic extract was evaluated using ethanol/HCl, non-steroidal anti-inflammatory drug, stress-induced-ulcer and chronic ulcer-model. The effects on gastric content volume, pH, total acidity and mucus stomach production were evaluated in the pylorus ligated-model. The C. langsdorffii extract obtained from leaves (50, 250 or 500 mg/kg) reduced the injured area compared to control group in all experiments. The extract showed a significant decrease in the total gastric juice acidity and an increase in mucus production (500 mg/kg) when compared to vehicle. Among isolated compounds (30 mg/kg) α-humulene, β-caryophyllene and caryophyllene oxide showed greater gastroprotective activity in the ethanol/HCl induced ulcer model. The data herein obtained shown that C. langsdorffii leaves extract and isolated compounds from it, presented gastroprotective properties in different animal models of gastric ulcer. These effects may be associated with the ability of the extract to decrease gastric secretion and increase the mucus production.