Antibacterial activity of free or encapsulated selected phenylpropanoids against Escherichia coli and Staphylococcus epidermidis.

AIMS: Antibacterial activities of phenylpropenes (PPs) (eugenol, isoeugenol, estragole and trans-anethole) and hydroxycinnamic acids (HCAs) (p-coumaric, caffeic and ferulic acids) were assessed against Escherichia coli and Staphylococcus epidermidis. Effect of cyclodextrin and liposome encapsulation on the PPs activity was also evaluated. METHODS AND RESULTS: All PPs inhibited the bacterial growth in the hundred micromolar range, while HCAs did not, as determined by broth macrodilution. Anethole and estragole showed a higher efficiency than eugenol and isoeugenol, and E. coli was more susceptible than S. epidermidis. Hydroxypropyl-ß-cyclodextrin/PP complexes and anethole-loaded Lipoid S100-liposomes were prepared by freeze-drying and ethanol injection respectively. Both formulations were substantially less active than free PPs. For instance, E. coli growth inhibition was about 14% for all HP-ß-CD/PP complexes evaluated at MIC50 values of free PPs (P < 0·05), and about 12% for liposomal anethole evaluated at minimal bactericidal concentration value of free anethole (P < 0·05). CONCLUSIONS: Hydrophobicity appears to be crucial for PPs antibacterial activity. Encapsulation in cyclodextrin and liposome seems to retain the PPs preventing their interaction with bacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: This study highlights the structural features of simple phenylpropanoids related to their antibacterial activity. The limitations of conventional encapsulation systems on the activity of PPs should be considered in future applications.

Ferutinin stability in human plasma and interaction with human serum albumin.

Ferutinin is a potent phytoestrogen extracted from plants of the genus Ferula. The biological activity of this sesquiterpene is associated with the esterification of p-hydroxybenzoic acid with the daucane alcohol, jaeschkeanadiol. A HPLC method was developed to investigate the stability of ferutinin in acidic and basic solutions (pH 1.5 and 9.0, respectively), in buffer (pH 7.4) as well as in serial dilutions of albumin and in human plasma. The degradation of ferutinin was relatively slow at physiological pH 7.4 compared with low or high pH. Ferutinin was fully stable in human plasma as well as in albumin solution and the stability increased with albumin concentration. The binding of ferutinin to albumin was investigated by fluorescence spectroscopy. Ferutinin decreased the fluorescence of HSA and that of the only tryptophan residue located in domain IIA. As a result of the interaction between ferutinin and albumin, the binding of bilirubin decreased. The stability of ferutinin in plasma is attributable to ferutinin-albumin binding.

Effect of cucurbitacins on bilirubin-albumin binding in human plasma.

The aim of this study is to investigate the effect of three cucurbitacins (Cuc) E, D and I on the bilirubin-albumin binding, both in human serum albumin (HSA) and in plasma. Bilirubin-HSA solution and plasma free of cucurbitacins were prepared as well as others containing serial concentrations of cucurbitacins. The concentration of unbound bilirubin was determined in bilirubin-HSA solution and the direct and total bilirubin concentrations were measured in plasma (with normal or elevated bilirubinemia) by Jendrassik and Grof method. In the conditions we adopted Cuc E and D (to a lesser extent), decreased the levels of unbound bilirubin in bilirubin-HSA solution and decreased direct bilirubin concentration and total bilirubin concentration in plasma in a dose-dependent manner while Cuc I had no effect. The effect of Cuc is related to the presence of native HSA. Thus, when albumin was absent or has been denatured by heating or by urea, Cuc E did not modify bilirubin levels, suggesting that the native structure of albumin is essential for such activity. The interaction of HSA with Cuc E was investigated by fluorescence spectroscopy. Cuc E increased the intrinsic fluorescence of the protein and the magnitude of fluorescence intensity of bilirubin-albumin complex. We concluded that Cuc E and D produced a rearrangement in the structure of albumin, particularly in the domain-II, resulting in an increase in the binding of bilirubin to albumin regardless to whether it's conjugated to glucuronic acid or unconjugated.