In vitro activity of natural phenolic compounds against fluconazole-resistant Candida species: a quantitative structure-activity relationship analysis.

AIMS: To evaluate the antifungal activity and to analyse the structure-activity relationship of eleven natural phenolic compounds against four Candida species which are resistant to fluconazole. METHODS AND RESULTS: Four different species of Candida isolates were used: Candida albicans, Candida krusei, Candida tropicalis and Candida dubliniensis. The phenolic compound carvacrol showed the highest anti-Candida bioactivity, followed by thymol and isoeugenol. The obtained minimum inhibitory concentration (MIC) values obtained were used in a quantitative structure-activity relationship (QSAR) analysis where the electronic, steric, thermodynamic and topological descriptors served as dependent variables. According to the descriptors obtained in this QSAR study, the antifungal activity of phenols has a first action specific character which is based on their interaction with plasma or mitochondrial membranes. The second action is based on a steric descriptor-the maximal and minimal projection of the area-which could explain the inability of some phenolic compounds to be biotransformed to quinones methylene by Candida species. CONCLUSIONS: According to the descriptors obtained in this QSAR study, the anti-Candida activity of ortho-substituted phenols is due to more than one action mechanism. The anti-Candida activity of phenolic compounds can be predicted by their molecular properties and structural characteristics. SIGNIFICANCE AND IMPACT OF THE STUDY: These results could be employed to predict the anti-Candida activity of new phenolic compounds in the search for new alternatives or complementary therapies to combat against candidiasis.

Inhibitory effect of Thymus vulgaris and Origanum vulgare essential oils on virulence factors of phytopathogenic Pseudomonas syringae strains.

Pseudomonas syringae is a phytopathogenic bacterium that causes lesions in leaves during the colonisation process. The damage is associated with production of many virulence factors, such as biofilm and phytotoxins. The essential oils of Thymus vulgaris (thyme) and Origanum vulgare (oregano) have been demonstrated to inhibit P. syringae. The aim of this study was to investigate the effects of T. vulgaris and O. vulgare essential oils on production of virulence factors of phytopathogenic P. syringae strains, including anti-biofilm and anti-toxins activities. The broth microdilution method was used for determination of MIC and biofilm inhibition assays. Coronatine, syringomycin and tabtoxin were pheno- and genotypically evaluated. Both oils showed good inhibitory activity against P. syringae, with MIC values from 1.43 to 11.5 mg·ml-1 for thyme and 5.8 to 11.6 mg·ml-1 for oregano. Biofilm formation, production of coronatine, syringomycin and tabtoxin were inhibited by thyme and oregano essential oil in most strains. The results presented here are promising, demonstrating the bactericidal activity and reduction of virulence factor production after treatment with thyme and oregano oil, providing insight into how they exert their antibacterial activity. These natural products could be considered in the future for the control of diseases caused by P. syringae.

Achyrocline satureioides (LAM.) DC (Marcela): antimicrobial activity on Staphylococcus spp. and immunomodulating effects on human lymphocytes.

Achyrocline satureioides (LAM.) DC (Compositae) is a sub-bush original from America and distributed in Europe and Africa. It is mainly used in infusions, as digestive, sedative among others and has antimicrobial and antiviral properties. A research was made into the anti-microbial activity of the A. satureioides decoction on the Staphylococcus spp strains. They were isolated from 18 patients with acne lesions and from 7 patients infected with Staphylococcus spp. (5 strains were taken from catheters and 2 from wounds). The strains were classified through biochemical tests and then were seeded in triptein-soy agar with or without decoction to observe the antibacterial activity. On the other hand, cultures of lymphocytes were made from those patients who displayed infections caused by Staphylococcus spp. and from 12 control non-infected individuals. The lymphocytes were stimulated with decoction or PHA-M. Among the expanded, CD8+ T cells, with anti-human CD8 monoclonal antibody were the outstanding ones by indirect IF. The A. satureiodes decoction inhibited 95% of the isolated Staphylococcus spp. strains and stimulated the lymphocyte expansion, of which 40% were CD8+ T cells. The A. satureiodes decoction showed anti-microbial activity and resulted to be an immunostimulating agent on CD8+ T cells, with lesser mitogenic effects than PHA-M.

Immunomodulating properties of Minthostachys verticillata on human lymphocytes and basophils.

BACKGROUND: Minthostachys verticillata (Griseb.) Epling is a South American traditional medicinal herb used as digestive, anti-spasmodic, anti-inflammatory and bronchial dilator agent among other uses. Its anti-microbial activity against staphylococcal strains and its anti-viral properties against HVS-1 and strain RC/79 of PrV have been demonstrated. OBJECTIVE: To determine the immunomodulating ability of M. verticillata decoction and essential oil. As a complementary study, the main constituents of the essential oil were identified. MATERIALS AND METHODS: Lymphocyte-proliferating activity of both vegetal derivatives was tested and compared with cellular expansion induced by PHA, Pokeweed, CGB in cytomorphological study. A non-stimulate culture was used as control reference. The score of lymphocyte clusters and colonies was performed using the method described by Lange. Among proliferated cells, LT CD8+ subpopulation was characterized by direct immunofluorescence. The in vitro degranulant ability of the vegetal fractions was tested on basophils from allergic and non-allergic individuals sensitized to environmental fungi. Essential oil components of M. verticillata were identified by gas chromatography technique. RESULTS: M. verticillata derivatives reached higher proliferation levels compared to non-stimulated cultures, showed mitogenic activity and induced cluster and colony formation similar to PHA, Pokeweed and CGB. Cells that proliferated after stimulation with derivatives showed 40% of LT CD8+. Tested concentrations of decoction and essential oil did not reach minimum degranulation indexes over basophils, from both allergic and non-allergic individuals. Gas chromatography analysis revealed the presence of pulegone and menthone as the main constituents. CONCLUSIONS: M. verticillata derivatives were mitogenic over LT, inducing significant cluster and colony formation. There was no evidence of degranulating ability over basophils at the concentrations tested. We assume that the derivatives from M. verticillata would induce Th1 deviation in cellular cultures from allergic patients, which would diminish hypersensitivity reactions. Some of the compounds of the essential oil revealed by gas chromatography analysis may be responsible of the biological activity of these products.