Health services across the world face an unprecedented situation as a result of a global COVID‐19 outbreak. Urgent joined research efforts regarding the SARS‐COV‐2 rapid tests, accurate diagnosis, especially early recognition, and effective treatment of life‐threatening complications would be highly desirable for humanity and medical workforce all over the world that try to combat a current global pandemic threat. Due to indirect complex effect, intensified COVID‐19 therapies and multi‐drug treatment, it is believed that some oral conditions could be aggravated by COVID‐19 disease, particularly those with autoimmune aetiology, linked to compromised immune system or long‐term pharmacotherapy.

There is a growing body of evidence that flavonoids show antibacterial activity against both Gram-positive and Gram-negative bacteria. The mechanisms of action of phenolic compounds on bacterial cell have been partially attributed to damage to the bacterial membrane, inhibition of virulence factors such as enzymes and toxins, and suppression of bacterial biofilm formation. What is more, some natural polyphenols, aside from direct antibacterial activity, exert a synergistic effect when combined with common chemotherapeutics. Many studies have proved that in synergy with antibiotics plant flavonoids pose a promising alternative for therapeutic strategies against drug resistant bacteria. In this review most recent reports on antimicrobial action of polyphenols on Staphylococcus aureus strains are described, highlighting where proven, the mechanisms of action and the structure–activity relationships. Since many reports in this field are, to some extent, conflicting, a unified in vitro and in vivo susceptibility testing algorithms should be introduced to ensure the selection of effective antibacterial polyphenolic compounds with low cytotoxicity and minimal side effects.

Phenolic compounds constitute one of the most promising and ubiquitous groups with many biological activities. Synergistic interactions between natural phenolic compounds and antibiotics could offer a desired alternative approach to the therapies against multidrug-resistant bacteria. The objective of the presented study was to assess the antibacterial potential of caffeic acid (CA) alone and in antibiotic-phytochemical combination against Staphylococcus aureus reference and clinical strains isolated from infected wounds. The caffeic acid tested in the presented study showed diverse effects on S. aureus strains with the minimum inhibitory concentration (MIC) varied from 256 μg/mL to 1024 μg/mL. The supplementation of Mueller-Hinton agar (MHA) with 1/4 MIC of CA resulted in augmented antibacterial effect of erythromycin, clindamycin, and cefoxitin and to the lesser extent of vancomycin. The observed antimicrobial action of CA seemed to be rather strain than antibiotic dependent. Our data support the notion that CA alone exerts antibacterial activity against S. aureus clinical strains and has capacity to potentiate antimicrobial effect in combination with antibiotics. The synergy between CA and antibiotics demonstrates its potential as a novel antibacterial tool which could improve the treatment of intractable infections caused by multidrug-resistant strains.

Abstract:The objective of this study was to assess in vitro the antimicrobial activity of ethanolic extract of Polish propolis (EEPP) against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates. The combined effect of EEPP and 10 selected antistaphylococcal drugs on S. aureus clinical cultures was also investigated. EEPP composition was analyzed by a High Performance Liquid Chromatography (HPLC) method. The flavonoid compounds identified in Polish Propolis included flavones, flavonones, flavonolols, flavonols and phenolic acids. EEPP displayed varying effectiveness against twelve S. aureus strains, with OPEN ACCESSMolecules 2013, 18 9624 minimal inhibitory concentration (MIC) within the range from 0.39 to 0.78 mg/mL, determined by broth microdilution method. The average MIC was 0.54 ± 0.22 mg/mL, while calculated MIC 50 and MIC 90 were 0.39 mg/mL and 0.78 mg/mL, respectively. The minimum bactericidal concentration (MBC) of the EEPP ranged from 0.78 to 3.13 mg/mL. The in vitro combined effect of EEPP and 10 antibacterial drugs was investigated using disk diffusion method-based assay. Addition of EEPP to cefoxitin (FOX), clindamycin (DA), tetracycline (TE), tobramycin (TOB), linezolid (LIN), trimethoprim+sulfamethoxazole (SXT), penicillin (P), erythromycin (E) regimen, yielded stronger, cumulative antimicrobial effect, against all tested S. aureus strains than EEPP and chemotherapeutics alone. In the case of ciprofloxacin (CIP) and chloramphenicol (C) no synergism with EEPP was observed.

Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate-binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3-O-β-d-rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB-MDA-231, selected as representative for triple-negative breast cancer and (ii) MCF-7 used as a well-characterized model of HER2-negative breast cancer. To assess the cytocompatibility of rutin against non-cancer cells, primary human mammary fibroblasts were used as control and non-target cells. In MDA-MB-231 cells, 20 μM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p < 0.05) increased the anticancer activity of both chemotherapeutics, at 24-48-72 h, and decreased the activity of the adenosine triphosphate-binding cassette transporters, namely, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Flow cytometry analysis showed 20 μM and 50 μM rutin arrested cell cycle at G2/M and G0/G1 phases, respectively, significantly promoting cell apoptosis. Rutin, via non-selective inhibition of P-gp and BCRP pumps, efficiently reverses multidrug resistance and restores chemosensitivity to cyclophosphamide and cyclophosphamide of human chemoresistant, triple-negative breast cancer cells, successfully arresting cell cycle progression. Copyright © 2017 John Wiley & Sons, Ltd.