Vascular smooth muscle cell (VSMC) proliferation contributes to the development of atherosclerosis. Red wine consumption due to the polyphenol content has been reported to counteract atherosclerosis progression possibly through inhibition of VSMC proliferation, among other mechanisms. In this study we investigate the antiproliferative activity of four wine polyphenols: resveratrol, quercetin, ethyl gallate, and (+)-catechin in rat aortic VSMC. All four polyphenols inhibited serum-induced VSMC proliferation when applied as a single treatment. To further address a potential synergistic action of the investigated polyphenols, the antiproliferative effect of different combinations in equimolar, as well as equipotent ratios were quantified. The IC₅₀ values of single polyphenols regarding the inhibition of VSMC proliferation ranged from 49.58 µM to 86.06 µM. However, apparent inhibitory efficacy of each compound increased by a factor of 10.4 in the quadruple equipotent mixture, as calculated from the dose-reduction index. Thus, the effective IC₅₀ values of each of the four mixture constituents ranged from 4.76 µM to 8.27 µM. The calculated combination index (CI, where CI <, =, or > 1 indicate synergy, additivity, or antagonism, respectively) values of equimolar combinations of the polyphenols indeed indicated mainly synergy (CI ranging from 0.24 ± 0.01 to 1.51 ± 0.13). Optimized equipotent mixture showed enhanced synergy (CI ranging from 0.18 ± 0.04 to 1.36 ± 0.26). In conclusion, we show for the first time that four major polyphenols from wine synergistically inhibit VSMC proliferation.

. In the fosfomycin group, MRSA was detectable in 2 out of 10 (20%) animals (3.42 ؋ 10 2 and 1.51 ؋ 10 3 CFU/g of bone). Vancomycin was superior to the no-drug control (P ‫؍‬ 0.002), and fosfomycin was superior to the no-drug control and vancomycin (P < 0.001). The cultures from the wires were positive in all untreated animals (median, 2.5 ؋ 10 3 CFU/implant), in 10 animals in the vancomycin group (median, 1.15 ؋ 10 3 CFU/ implant), and negative in all animals in the fosfomycin group. Based on the bacterial counts from the implants, vancomycin was not superior to the no-drug control (P ‫؍‬ 0.324), and fosfomycin was superior to the no-drug control and vancomycin (P < 0.001). No emergence of resistance was observed. In conclusion, it was demonstrated that fosfomycin monotherapy is highly effective for the treatment of experimental implant-associated MRSA osteomyelitis.

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The present study aimed to investigate the capacity of resveratrol (RV) delivered into macrophages by bacterial ghosts (BGs), representing intact empty nonliving envelopes of Gram-negative bacteria, to modulate nitric oxide (NO) production related to the presence of the pathogen-associated molecular patterns on the surface of BGs. Incubation of the murine macrophage cell line RAW 264.7 with BGs leads to a dose-dependent activation of inducible NO synthase. To modify BG-induced NO formation in RAW 264.7 cells by RV; BGs were loaded with RV (RV-BGs) and incubated with murine macrophages in a dose-dependent manner. RV-BGs delivering RV to the target macrophages significantly reduced BG-induced NO production with concentration of RV more than one order of magnitude lower than the amount of RV capable of reducing NO formation when applied directly. Moreover, no cytotoxic impact of BGs on the viability of RAW 264.7 cells added to macrophages alone or loaded with RV was detected after a mutual 24 h incubation, whereas cell viability slightly decreased (~10%) when RV concentrations of 30 lM alone were applied. The results obtained in the present study clearly indicate that the intracellular delivery of RV by BGs significantly enhances the total RV effect.

In a bioassay-guided approach the chemical composition of rhizomes of Metaxya rostrata (Kunth C. Presl) was studied for the first time. Investigations of the cytotoxicity of extracts and fractions on SW480 colorectal carcinoma cells resulted in the isolation of two polyphenols Ð cinnamtannin B-1 and aesculitannin B. The structures of the compounds were elucidated by different NMR experiments. Additionally, sugars, common sterols, such as sitosterol, stigmasterol and campesterol, as well as chlorogenic acid and caffeic acid were identified in Metaxya rostrata.