tetracycline and myricetin

Liquidambar styraciflua L., ALTINGIACEAE, popularly known as sweet gum or alligator tree, is an aromatic tree with a natural distribution in North America and acclimated in Brazil. In traditional medicine, L. styraciflua L is used for the treatment of stomach disorders, wounds, and coughs. The present study was designed to investigate the biological potential and chemical profile of extracts obtained from aerial parts of L. styraciflua L. The chemical profile was established using liquid chromatography-mass spectrometry analysis and the extracts were tested for total phenolics, flavonoids, and tannins using spectrophotometric assays. The anti-inflammatory activity of L. styraciflua L was tested using an inhibition of hyaluronidase enzyme assay, and cytotoxic activities were tested by the 3-(4,5-dimethylthiazol-2 yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The synergy between the plant extracts with ciprofloxacin and tetracycline was studied by the checkerboard assay method against eight bacterial strains.The phytochemical investigation showed that the leaves and stem are rich in phenolics compounds (1419.34-1614.02 mg GAE/g, 875.21-1557.57 mg GAE/g, respectively), mainly flavonoids and hydrolyzable tannins. The samples of the stem exhibited the best anti-inflammatory activity. The butanol fraction of the stem was better than the commercial propolis extract. The hydroalcoholic extract of the stem and the propolis did not exhibit significant differences (p < 0.05) at any of the concentrations tested. A synergistic interaction was observed against the Gram-positive bacterial Enterococcus faecalis (hydroalcoholic extract of leaves and tetracycline) and Staphylococcus aureus (hydroalcoholic extract of stem and tetracycline). The IC50 values obtained for the extracts indicate the absence of toxicity and moderate cytotoxic for the hydroalcoholic extract of the stem. On the basis of our findings, L. styaciflua may be considered as a potential therapeutic source with high anti-inflammatory activity and synergistic interactions with antibiotics against bacteria.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antioxidants; Chlorocebus aethiops; Enterococcus faecalis; Flavonoids; Gallic Acid; Hydrolysis; Inhibitory Concentration 50; Liquidambar; Medicine, Traditional; Microbial Sensitivity Tests; Phenols; Phytochemicals; Plant Extracts; Plant Leaves; Plant Stems; Quercetin; Staphylococcus aureus; Tannins; Tetracycline; Vero Cells

Combined results of theoretical molecular dynamic simulations and in vitro spectroscopic (circular dichroism and fluorescence) studies are presented, providing the atomistic and secondary structure details of the process by which a selected small molecule may destabilize the β-sheet ordered "amyloid" oligomers formed by the model undecapeptide of amyloid β-peptide 25-35 [Aβ(25-35)]. Aβ(25-35) was chosen because it is the shortest fragment capable of forming large β-sheet fibrils and retaining the toxicity of the full length Aβ(1-40/42) peptides. The conformational transition, that leads to the formation of β-sheet fibrils from soluble unordered structures, was found to depend on the environmental conditions, whereas the presence of myricetin destabilizes the self-assembly and antagonizes this conformational shift. In parallel, we analyzed several molecular dynamics trajectories describing the evolution of five monomer fragments, without inhibitor as well as in the presence of myricetin. Other well-known inhibitors (curcumin and (-)-tetracycline), found to be stronger and weaker Aβ(1-42) aggregation inhibitors, respectively, were also studied. The combined in vitro and theoretical studies of the Aβ(25-35) self-assembly and its inhibition contribute to understanding the mechanism of action of well-known inhibitors and the peptide amino acid residues involved in the interaction leading to a rational drug design of more potent new molecules able to antagonize the self-assembly process.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Circular Dichroism; Curcumin; Flavonoids; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Models, Molecular; Peptide Fragments; Protein Structure, Secondary; Spectrometry, Fluorescence; Temperature; Tetracycline

In this study the in vitro activities of seven antibiotics (ciprofloxacin, ceftazidime, tetracycline, trimethoprim, sulfamethoxazole, polymyxin B and piperacillin) and six phytochemicals (protocatechuic acid, gallic acid, ellagic acid, rutin, berberine and myricetin) against five P. aeruginosa isolates, alone and in combination are evaluated. All the phytochemicals under investigation demonstrate potential inhibitory activity against P. aeruginosa. The combinations of sulfamethoxazole plus protocatechuic acid, sulfamethoxazole plus ellagic acid, sulfamethoxazole plus gallic acid and tetracycline plus gallic acid show synergistic mode of interaction. However, the combinations of sulfamethoxazole plus myricetin shows synergism for three strains (PA01, DB5218 and DR3062). The synergistic combinations are further evaluated for their bactericidal activity against P. aeruginosa ATCC strain using time-kill method. Sub-inhibitory dose responses of antibiotics and phytochemicals individually and in combination are presented along with their interaction network to suggest on the mechanism of action and potential targets for the phytochemicals under investigation. The identified synergistic combinations can be of potent therapeutic value against P. aeruginosa infections. These findings have potential implications in delaying the development of resistance as the antibacterial effect is achieved with lower concentrations of both drugs (antibiotics and phytochemicals).

Topics: Anti-Bacterial Agents; Berberine; Ceftazidime; Ciprofloxacin; Drug Therapy, Combination; Ellagic Acid; Flavonoids; Gallic Acid; Hydroxybenzoates; Microbial Sensitivity Tests; Piperacillin; Polymyxin B; Pseudomonas aeruginosa; Rutin; Sulfamethoxazole; Tetracycline; Trimethoprim

Inhibition of the accumulation of amyloid beta-peptide (Abeta) and the formation of beta-amyloid fibrils (fAbeta) from Abeta, as well as the destabilization of preformed fAbeta in the CNS would be attractive therapeutic targets for the treatment of Alzheimer's disease (AD). We previously reported that nordihydroguaiaretic acid (NDGA) and wine-related polyphenols inhibit fAbeta formation from Abeta(1-40) and Abeta(1-42) as well as destabilizing preformed fAbeta(1-40) and fAbeta(1-42) dose-dependently in vitro. Using fluorescence spectroscopic analysis with thioflavin T and electron microscopic studies, we examined the effects of polymeric polyphenol, tannic acid (TA) on the formation, extension, and destabilization of fAbeta(1-40) and fAbeta(1-42) at pH 7.5 at 37 degrees C in vitro. We next compared the anti-amyloidogenic activities of TA with myricetin, rifampicin, tetracycline, and NDGA. TA dose-dependently inhibited fAbeta formation from Abeta(1-40) and Abeta(1-42), as well as their extension. Moreover, it dose-dependently destabilized preformed fAbetas. The effective concentrations (EC50) of TA for the formation, extension and destabilization of fAbetas were in the order of 0-0.1 microM. Although the mechanism by which TA inhibits fAbeta formation from Abeta as well as destabilizes preformed fAbeta in vitro is still unclear, it could be a key molecule for the development of therapeutics for AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Flavonoids; Kinetics; Masoprocol; Microscopy, Electron; Rifamycins; Tannins; Tetracycline; Thermodynamics