title: Campomanesia adamantium Peel Extract in Antidiarrheal Activity: The Ability of Inhibition of Heat-Stable Enterotoxin by Polyphenols.
abstract: Campomanesia adamantium (Myrtaceae) is a medicinal plant distributed in Brazilian Cerrado. Different parts of this plant are used in popular medicine for treatment of several diseases like fever, diarrhea, hypercholesterolemia and rheumatism. The aim of this work was to evaluate the inhibition of heat-stable enterotoxin type A (STa) by gallic acid present in the peel of C. adamantium fruit and assays to assess the antidiarrheal activity, anti-inflammatory and cytotoxic properties of peel extract using the T84 cell line model. The possible inhibition exerted by the gallic acid of the peel extract on the STa peptide was inferred by molecular dynamics simulations. The antidiarrheal effects were investigated measuring cGMP accumulation in cells after stimulation by STa toxin and antibacterial activity was assessed. The anti-inflammatory activity was assessed by inhibition of COX-1 and COX-2. MTT and LDH assays were used to evaluate any possible cytotoxic action while the CyQUANT test was used to investigate the effect on cell proliferation. A representation showing how the possible interactions between STa and the gallic acid of the extract might reduce the action of the enterotoxin is presented. C. adamantium peel extract significantly decreased the levels of cGMP in T84 cells. However, no effect on the species of microorganisms was observed. The extract also inhibited COX-1 (IC50 255.70 ± 0.04 ng/mL) and COX-2 (IC50 569.50 ± 0.11 ng/mL) enzymes. Cytotoxicity assay have shown significant changes in cells treated with the extract, which inhibited the cell proliferation until 72 hours of treatment. Direct interactions of phenolic compounds present in the extract with the STa toxin may limit its activity. Curative effect in the diarrhea treatment and its anti-inflammatory action is based on the pharmacological properties, mechanism of action of the C. adamantium peel extract, and no toxic effects of the peel extract presented on this work.
authors.affiliation: Department of Pharmacology, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Caroline Honaiser
authors.initials: CH
authors.lastname: Lescano
authors.affiliation: Institute of Chemistry, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Ivan Pires
authors.initials: IP
authors.lastname: de Oliveira
authors.affiliation: Department of Pharmacology, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Zaminelli
authors.affiliation: Faculty of Biological and Environmental Sciences, Federal University of Grande Dourados, Dourados, Mato Grosso do Sul, Brazil.
authors.forename: Débora da Silva
authors.initials: DD
authors.lastname: Baldivia
authors.affiliation: Faculty of Engineering, Federal University of Grande Dourados, Dourados, Mato Grosso do Sul, Brazil.
authors.forename: Luan Ramos
authors.initials: LR
authors.lastname: da Silva
authors.affiliation: Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Mauro
authors.initials: M
authors.lastname: Napolitano
authors.affiliation: Department of Pharmacology, University of Campinas, Campinas, São Paulo, Brazil.
authors.forename: Camila Bitencourt Mendes
authors.initials: CB
authors.lastname: Silvério
authors.affiliation: Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Nilton
authors.initials: N
authors.lastname: Lincopan
authors.affiliation: Faculty of Engineering, Federal University of Grande Dourados, Dourados, Mato Grosso do Sul, Brazil.
authors.forename: Eliana Janet
authors.initials: EJ
authors.lastname: Sanjinez-Argandoña
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000930:Antidiarrheals / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D004768:Enterotoxins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005419:Flavonoids / Q000032:analysis; D005638:Fruit / Q000737:chemistry / Q000378:metabolism; D005707:Gallic Acid / Q000737:chemistry / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D027822:Myrtaceae / Q000737:chemistry* / Q000378:metabolism; D010636:Phenols / Q000032:analysis; D010936:Plant Extracts / Q000737:chemistry*; D059808:Polyphenols / Q000737:chemistry / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000930:Antidiarrheals; D004768:Enterotoxins; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D005707:Gallic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2