Three extracts of defatted seeds of Oenothera paradoxa Hudziok, aqueous extract, 60% ethanolic extract, and 30% isopropanolic extract, differing by their total content of phenolic compounds and by their contents of individual polyphenols, were investigated in this study. The extracts exerted cytotoxic action on HTB-140 human skin melanoma cells. After 24 h of incubation, IC(50) values of 169.7 +/- 5.9 mug/mL, 72.4 +/- 3.8 mug/mL, and 155.3 +/- 6.3 mug/mL were obtained for HTB-140 cells with the aqueous extract, 60% ethanolic extract, and 30% isopropanolic extract at the tested concentrations (5-200 mug/mL), respectively, while IC(50) for normal fibroblast cells NHDFs was not attained. Moreover, for HTB-140 cells, LD(50)(concentration at which 50% of cells were dead) of 89.2 +/- 4.3 mug/mL and 181.4 +/- 6.5 mug/mL were obtained with 60% ethanolic extract and 30% isopropanolic extract, respectively. In melanoma cells, all three extracts caused a concentration-dependent increase of ROS production, GSH, and ATP lowering, and appearance of phosphatidylserine on the external surface of cellular membranes where it was bound to annexin V-FITC; furthermore, apoptosis without activation of caspase-3 took place. The most effective was 60% ethanolic extract, which had the greatest total content of phenolic compounds and the greatest content of pentagalloyloglucose (PGG).

Adhesion and migration of leukocytes into the surrounding tissue are crucial steps in inflammation, immunity and atherogenesis. Expression of cell adhesion molecules by endothelial cells plays a role in these processes. Propionate is a naturally occurring short chain fatty acid produced by bacterial fermentation of dietary fibre. High intake of dietary fibre has been associated with an improved bowel function and with a reduced risk of cardiovascular disease. However, the molecular mechanisms responsible for these effects remain unknown. In this study, the effects of propionate on the expression of endothelial leukocyte adhesion molecules by cytokine-stimulated human umbilical vein endothelial cells (HUVEC) were investigated. Pretreatment of HUVEC with propionate significantly inhibited the tumor necrosis factor alpha (TNF-alpha)-induced expression of vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) in a time- and dose-dependent manner. At 10 mM, propionate also inhibited the interleukin-1 (IL- 1)-mediated VCAM-1 and ICAM-1 expression, with the latter effect being more pronounced, as well as decreased the TNF-alpha-induced VCAM-1 and ICAM-1 mRNA expression in a similar manner. The decrease in VCAM-1 and ICAM-1 expression was associated with a reduction of adherence of monocytes and lymphocytes to the cytokine-stimulated HUVEC. In addition, propionate significantly inhibited the TNF-alpha-induced activation of nuclear factor-kappa B (NF-kappaB) and significantly increased the expression of peroxisome proliferator-activated receptor alpha (PPARalpha) in HUVEC. These results demonstrate that propionate may have antiinflammatory and possibly antiatherogenic properties. Our findings warrant further investigation into the therapeutic effects of propionate on a number of pathological events nvolving leukocyte recruitment.

BACKGROUND: Relatively high concentrations of acrylamide in commonly ingested food products, such as French fries, potato chips, or cereals, may constitute a potential risk to human health. OBJECTIVE: The objective of this pilot study was to investigate the possible connection between chronic ingestion of acrylamide-containing potato chips and oxidative stress or inflammation. DESIGN: Fourteen healthy volunteers (mean age: 35 y; 8 women and 6 smokers of >20 cigarettes/d) were given 160 g of potato chips containing 157 mg of acrylamide daily for 4 wk. RESULTS: An increase in acrylamide-hemoglobin adducts in blood was found in all the study subjects, with a mean of 43.1 pmol/L/g hemoglobin (range: 27-76; P < 0.01) in nonsmokers and 59.0 pmol . L(-1). g(-1) hemoglobin (range: 43-132; P < 0.05) in smokers. Concurrently, a significant increase (P < 0.01) in the oxidized LDL, high-sensitivity interleukin-6, high-sensitivity C-reactive protein, and gamma-glutamyltransferase concentrations was observed in both smokers and nonsmokers. A significant increase in reactive oxygen radical production by monocytes, lymphocytes, and granulocytes and an increase in CD14 expression in macrophages (P < 0.001) were found after intake of potato chips. Twenty-eight days from the discontinuation of the experiment, the variables under study decreased to some extent. It has been shown also that acrylamide increases the production of reactive oxygen species in isolated human monocyte-macrophages in vitro and decreases the cellular glutathione concentration. CONCLUSION: These novel findings seem to indicate that chronic ingestion of acrylamide-containing products induces a proinflammatory state, a risk factor for progression of atherosclerosis.

In this study, for the first time, we used the in vitro metallopeptidase model for the identification of a potential novel activity of defatted evening primrose seed extracts. Prepared extracts of different polarity (aqueous, 60% ethanolic, isopropanolic, and 30% isopropanolic) at concentrations of 1.5-100 mug/mL exhibited a significant and dose dependent inhibition of three tested enzymes. The 50% inhibition of enzymes activity showed that aminopeptidase N (APN) was the enzyme affected to the greatest extent with IC 50 at the level of 2.8 mug/mL and 2.9 mug/mL for aqueous and 30% isopropanolic extracts, respectively. The activity of neutral endopeptidase (NEP) was quite strongly inhibited by the extracts as well. The HPLC-DAD analysis and bioguided fractionation led to the identification of four active compounds:(-)-epicatechin gallate, proanthocyanidin B3, oenothein B, and penta- O-galloyl-beta- d-glucose (PGG). Oenothein B has been shown previously to inhibit metallopeptidases. The three other compounds are known to inhibit angiotensin-converting enzyme (ACE), but they have not been previouly reported to inhibit the NEP and APN activity. PGG and procyanidins with different degrees of polymerization, as the dominating compounds in O. paradoxa seeds, seemed to play a role in the crude extract activity.

Background: High-dose statins are used in acute coronary syndromes (ACS) to reduce inflammation. The aim of the study was the evaluation of the influence of low-dose atorvastatin (20 mg) on selected inflammatory parameters and clinical outcomes after ACS. Methods: Seventy eight patients (pts) with ACS were randomly divided into group A (39 pts) taking atorvastatin, and group NA (39 pts) not taking any statin for the following six weeks. C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and tumour necrosis factor alpha (TNFa) levels were measured on the first and the fifth days and six weeks after ACS. Results: There was no significant CRP and IL-6 level decrease in group A (CRP - 62%; IL-6 - 73%) or group NA (CRP - 44%; IL-6 - 62%). There was also no significant change in TNFa levels. The MCP-1 level finally reached the level of significant difference (p < 0.04). Cardiovascular events (MACE) and the restenosis rates did not differ between the groups. Conclusions: Low-dose atorvastatin does not have a significant influence on cooling down inflammation in ACS, and MCP-1 can be used as an early indicator of statin anti-inflammatory activity. Furthermore, it does not reduce MACE or restenosis rates despite its influence on MCP-1 levels.