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Therapeutic Potential of Limonium brasiliense Extracts in Helicobacter pylori-Associated Gastric Pathologies
Augusto Santos Borges1, Ana Carolina Guidi1, Mariana Nascimento de Paula1
1Department of Pharmacy, Laboratory of Pharmaceutical Biology, Palafito, Universidade Estadual de Maringá, Brazil.
Abstract:
Helicobacter pylori infection is related to several gastric pathologies, including gastritis, peptic ulcer, and gastric cancer. Substances capable of eradicating H. pylori have been subject to the attention of researchers. This study evaluated a fully characterized ethyl acetate fraction, obtained from the rhizomes of Limonium brasiliense, and its microparticulate pharmaceutical form against H. pylori, as well as their potential immunomodulatory and antitumor activities associated with H. pylori infection. Ultra-high-performance liquid chromatography analysis of ethyl acetate fraction indicated the presence of samaragenins A and B along with gallic acid, epigallocatechin, and epigallocatechin-3-O-gallate. Antioxidant activity showed half-maximum inhibitory concentration values of 5.7 (95% confidence interval: 5.21 - 6.83), 31.9 (95% confidence interval: 19.57 - 51.99), and 33.1 (95% confidence interval: 24.4 - 44.73) µg/mL for HOCl, O2 •-, and NO, respectively. Ethyl acetate fraction exerted minimal inhibitory concentration values of 1,024 and 128 µg/mL against the H. pylori (ATCC 43 504, clinical isolate H. pylori strain). In vivo treatments in mice with ethyl acetate fraction and microparticulate ethyl acetate fraction (100 mg/kg, in single daily doses for 20 consecutive days) improved gastric pathology in infected animals, reducing urease positivity (14.3% vs. 54.5% in untreated controls), inflammation (tumor necrosis factor alpha, interleukin 1β, and interleukin 6 reduced, p < 0.05), and morphological damage compared with the untreated control group. H. pylori urease was inhibited with half-maximum inhibitory concentration of 521.6 µg/mL (95% confidence interval: 419.2 - 649.0). In addition, ethyl acetate fraction showed antiproliferative activity against gastric adenocarcinoma cells (half cytotoxic concentration of 21.7, 95% confidence interval: 18.1 - 26.04). In Escherichia coli lipopolysaccharide-stimulated macrophages, ethyl acetate fraction reduced the tumor necrosis factor alpha and interleukin 6 production by 16% and 35%, respectively. These results indicate the potential of L. brasiliense as a source of compounds capable of attenuating gastric diseases related to H. pylori infection.
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