Therapeutic Potential of Limonium brasiliense Extracts in Helicobacter pylori-Associated Gastric Pathologies
Augusto Santos Borges, Ana Carolina Guidi, Mariana Nascimento de Paula, Eloisa Lorenzi Da Silva, Gabriel Jorge Fagundes, Marco Aurélio Valadão Fagundes, Rodrigo Rezende Kitagawa, Rita de Cássia Ribeiro Gonçalves, Daniela Cristina De Medeiros Araújo, João Carlos Palazzo de MelloHelicobacter 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 (EAF), obtained from the rhizomes of L. brasiliense and its microparticulate pharmaceutical form (mpEAF) against H. pylori, and in addition for potential immunomodulatory and antitumor activities associated with H. pylori infection. UHPLC analysis of EAF indicated the presence of samaragenins A and B beside gallic acid, (epi)gallocatechin, epigallocatechin-3-O-gallate. Antioxidant activity showed IC50 values of 5.7 (95% CI: 5.21–6.83), 31.9 (95% CI: 19.57–51.99), and 33.1 (95% CI: 24.4–44.73) µg/mL for HOCl, O2•− and NO, respectively. EAF exerts MIC values of 1024 and 128 µg/mL against the H. pylori (ATCC 43504, clinical isolate P7). In vivo treatments in mice with EAF and mpEAF (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), reducing inflammation (TNF-α, IL-1β, and IL-6 reduced, p < 0.05) and morphological damage compared with the untreated control group. <i>Helicobacter pylori</i> urease was inhibited with IC<sub>50</sub> of 521.6 µg/mL (95% CI: 419.2–649.0). In addition, EAF showed antiproliferative activity against gastric adenocarcinoma cells (CC<sub>50</sub> of 21.7, 95% CI: 18.1–26.04). In LPS-stimulated macrophages, EAF reduced the TNF-α and IL-6 production by 16% and 35%, respectively. These results indicate the potential of <i>L. brasiliense</i> as a source of compounds capable of attenuating gastric diseases related to <i>H. pylori</i> infection.