Anti-inflammatory, antimicrobial and antioxidant activities of Diospyros bipindensis (Gürke) extracts and its main constituents.

ETHNOPHARMACOLOGICAL RELEVANCE: Diospyros bipindensis (Gürke) stem bark is used in Cameroon by Baka Pygmies for the treatment of respiratory disorders. AIM OF THE STUDY: To assess the anti-inflammatory, antibacterial and antioxidant properties of constituents from the bark extracts through bioassay-guided fractionation. MATERIALS AND METHODS: The anti-inflammatory activity of extracts, fractions and pure compounds was assessed through the inhibition of the pro-inflammatory mediator nuclear factor-kappa B (NF-κB) transcriptional activity and nitric oxide (NO) production. DPPH, ABTS and ORAC assays were used for determining the antioxidant properties. The activity against Streptococcus pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli and Klebsiella pneumoniae, was evaluated on the basis of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) by the macrodilution method. RESULTS: The water extract showed antimicrobial activity against S. pneumoniae (MIC: 300 µg/ml) and S. pyogenes (MIC: 300 µg/ml). The dichloromethane extract efficiently inhibited NF-κB transcriptional activity and NO production and exhibited significant antioxidant activity in the ORAC assay. An interesting activity was also found against S. pneumoniae (MIC: 200 µg/ml), S. aureus (MIC: 400 µg/ml) and S. pyogenes (MIC: 200 µg/ml). The phytochemical investigation of the dichloromethane extract afforded plumbagin, canaliculatin, ismailin, betulinic acid and 4-hydroxy-5-methyl-coumarin as the main constituents. Plumbagin and ismailin were found to be responsible for the main biological activities observed. CONCLUSIONS: These results may provide a rational support for the traditional use of Diospyros bipindensis stem bark in the treatment of respiratory disorders, since the anti-inflammatory, antimicrobial and antioxidant compounds isolated from the dichloromethane extract were also present in the traditional water extract.

Antioxidant potential and radical-scavenging effects of flavonoids from the leaves of Psidium cattleianum grown in French Polynesia.

Psidium cattleianum J. Sabine (Myrtaceae) is a traditional medicinal plant in French Polynesia. The leaves and roots possess many medicinal properties. These effects may be correlated with the presence of antioxidant compounds. Seven flavonoids along with a benzoic acid were isolated from the leaves of P. cattleianum. The compounds indicated strong antioxidant and radical-scavenging activities in ALP, DPPH(·), ABTS(·-) and ORAC assays. This study demonstrates that the leaves of P. cattleianum possess main compounds with interesting antioxidant and radical-scavenging activities, as clarified by four biological assays. Our findings may justify the use of these leaves in the traditional medicine of French Polynesia. Among the total eight known compounds, reynoutrin and luteolin were isolated for the first time from the genus Psidium.

Xanthones from Gentianella amarella ssp. acuta with acetylcholinesterase and monoamine oxidase inhibitory activities.

Two new xanthone glycosides, corymbiferin 3-O-beta-D-glucopyranoside (1) and swertiabisxanthone-I 8'-O-beta- d-glucopyranoside (2), were isolated from Gentianella amarella ssp. acuta, along with eight known xanthones: triptexanthoside C, veratriloside, corymbiferin 1-O-glucoside, swertianolin, norswertianolin, swertiabisxanthone-I, bellidin, and bellidifolin, four of them identified for the first time in G. amarella ssp. acuta. The isolation was conducted mainly by centrifugal partition chromatography, and the structures of the isolated compounds were established on the basis of spectrometric data including 2D NMR and mass spectrometry. Xanthones were weakly active against acetylcholinesterase (AChE), except triptexanthoside C, which inhibited AChE with an IC(50) of 13.8 +/- 1.6 microM. Some compounds were active against monoamine oxidases (MAO): bellidin and bellidifolin showed interesting inhibitory activity of MAO A, while swertianolin, the 8-O-glucopyranoside form of bellidifolin, gave 93.6% inhibition of MAO B activity at 10(-5) M.

Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation in CYP2B6 slow metabolizers.

Methadone inhibits the cardiac potassium channel hERG and can cause a prolonged QT interval. Methadone is chiral but its therapeutic activity is mainly due to (R)-methadone. Whole-cell patch-clamp experiments using cells expressing hERG showed that (S)-methadone blocked the hERG current 3.5-fold more potently than (R)-methadone (IC50s (half-maximal inhibitory concentrations) at 37 degrees C: 2 and 7 microM). As CYP2B6 slow metabolizer (SM) status results in a reduced ability to metabolize (S)-methadone, electrocardiograms, CYP2B6 genotypes, and (R)- and (S)-methadone plasma concentrations were obtained for 179 patients receiving (R,S)-methadone. The mean heart-rate-corrected QT (QTc) was higher in CYP2B6 SMs (*6/*6 genotype; 439+/-25 ms; n=11) than in extensive metabolizers (non *6/*6; 421+/-25 ms; n=168; P=0.017). CYP2B6 SM status was associated with an increased risk of prolonged QTc (odds ratio=4.5, 95% confidence interval=1.2-17.7; P=0.03). This study reports the first genetic factor implicated in methadone metabolism that may increase the risk of cardiac arrhythmias and sudden death. This risk could be reduced by the administration of (R)-methadone.

Monoamine oxidase inhibitor properties of some benzazoles: structure-activity relationships.

Benzazoles containing two or three nitrogen atoms were screened for their inhibitory activity toward monoamine oxidases MAO-A and MAO-B. In order to clarify the mechanism of interaction of these compounds with the enzyme, their electronic structure was calculated at the ab initio level and the influence of lipophilicity on activity was investigated. The mode of binding of benzazoles to MAO-B appears different from that of previously investigated heterocycles.

Knowledge-based modeling of a legume lectin and docking of the carbohydrate ligand: the Ulex europaeus lectin I and its interaction with fucose.

Ulex europaeus isolectin I is specific for fucose-containing oligosaccharide such as H type 2 trisaccharide alpha-L-Fuc (1-->2) beta-D-Gal (1-->4) beta-D-GlcNAc. Several legume lectins have been crystallized and modeled, but no structural data are available concerning such fucose-binding lectin. The three-dimensional structure of Ulex europaeus isolectin I has been constructed using seven legume lectins for which high-resolution crystal structures were available. Some conserved water molecules, as well as the structural cations, were taken into account for building the model. In the predicted binding site, the most probable locations of the secondary hydroxyl groups were determined using the GRID method. Several possible orientations could be determined for a fucose residue. All of the four possible conformations compatible with energy calculations display several hydrogen bonds with Asp-87 and Ser-132 and a stacking interaction with Tyr-220 and Phe-136. In two orientations, the O-3 and O-4 hydroxyl groups of fucose are the most buried ones, whereas two other, the O-2 and O-3 hydroxyl groups are at the bottom of the site. Possible docking modes are also studied by analysis of the hydrophobic and hydrophilic surfaces for both the ligand and the protein. The SCORE method allows for a quantitative evaluation of the complementarity of these surfaces, on the basis of molecular lipophilicity calculations. The predictions presented here are compared with known biochemical data.