Although the exact role of quorum sensing (QS) in various stages of biofilm formation, maturation, and dispersal and in biofilm resistance is not entirely clear, the use of QS inhibitors (QSI) has been proposed as a potential antibiofilm strategy. We have investigated whether QSI enhance the susceptibility of bacterial biofilms to treatment with conventional antimicrobial agents. The QSI used in our study target the acyl-homoserine lactone-based QS system present inPseudomonas aeruginosaandBurkholderia cepaciacomplex organisms (baicalin hydrate, cinnamaldehyde) or the peptide-based system present inStaphylococcus aureus(hamamelitannin). The effect of tobramycin (P. aeruginosa,B. cepaciacomplex) and clindamycin or vancomycin (S. aureus), alone or in combination with QSI, was evaluated in variousin vitroandin vivobiofilm model systems, including two invertebrate models and one mouse pulmonary infection model.In vitrothe combined use of an antibiotic and a QSI generally resulted in increased killing compared to killing by an antibiotic alone, although reductions were strain and model dependent. A significantly higher fraction of infectedGalleria mellonellalarvae andCaenorhabditis eleganssurvived infection following combined treatment, compared to treatment with an antibiotic alone. Finally, the combined use of tobramycin and baicalin hydrate reduced the microbial load in the lungs of BALB/c mice infected withBurkholderia cenocepaciamore than tobramycin treatment alone. Our data suggest that QSI may increase the success of antibiotic treatment by increasing the susceptibility of bacterial biofilms and/or by increasing host survival following infection.

Polyphenolic compounds are widely distributed in higher plants and are an integral part of the human diet. Recent interest in these substances has been stimulated by their potential health benefits, which are believed to arise mainly from their antioxidant activity. In the past years, the antioxidant activity of flavonoids has been studied in detail. An important but often overlooked group of polyphenols is that of the proanthocyanidins. Therefore, the present review is focused mainly on the antioxidant activity of proanthocyanidins and its relevancy in vivo. The three most important mechanisms of their antioxidant action will be discussed, i.e. free radical scavenging activity, chelation of transition metals, and inhibition of enzymes. In addition, the protective role of proanthocyanidins against lipid peroxidation and peroxynitrite, as well as their antimicrobial properties will be discussed. To study the in vivo relevancy of the proanthocyanidin activities, the knowledge of their pharmacokinetic parameters is crucial. Although bioavailability and metabolism data on polyphenols in general and proanthocyanidins in particular are still largely unavailable, the first reports indicate that at least monomers and smaller oligomeric procyanidins are absorbed. There is also considerable scientific and public interest in the important role that antioxidants may play in health care, e.g. by acting as cancer chemopreventive and antiinflammatory agents and by reducing risk of cardiovascular mortality. Each of these aspects will be discussed, with special attention to the role of proanthocyanidins on apoptosis, gene expression and transcription factors, such as NF-kappa B.

Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. Based on their chemical structure, phytoestrogens can be classified into four main groups, i. e., isoflavonoids, flavonoids, stilbenes, and lignans. For each group, the chemistry, dietary sources and biotransformation of the most interesting compounds will be discussed. Since phytoestrogens are structurally very similar to the estrogen 17β-estradiol, they may exhibit selective estrogen receptor modulating activities. Therefore, special attention will be given to the hormonal effects of various isoflavonoids, including genistein, daidzein, coumestrol and equol, several prenylated flavonoids, especially 8-prenylnaringenin, and the stilbene resveratrol. Furthermore, their non-hormonal effects will be discussed briefly. Finally, the latest developments on the potential protective properties of phytoestrogens and phytoestrogen-containing foods against hormone-dependent breast and prostate cancers and cardiovascular diseases, and as estrogen replacement therapy for postmenopausal women will be discussed.