S-Nitrosylation of Paraxonase 1 (PON1) Elevates Its Hydrolytic and Antioxidant Activities.

Covalent binding between nitric oxide (NO) and a protein's free thiol group (SH) is termed protein S-nitrosylation. Protein S-nitrosylation is involved in cellular regulation mechanisms that underlie a wide range of critical functions, such as apoptosis, alteration of enzyme activities, and transcription-factor stability. Impaired protein S-nitrosylation is associated with a growing list of pathophysiological conditions, such as cardiovascular disease, multiple sclerosis, pulmonary hypertension, and sickle cell disease.

Towards a Consensus on Alzheimer's Disease Comorbidity?

Alzheimer's disease (AD) is often comorbid with other pathologies. First, we review shortly the diseases most associated with AD in the clinic. Then we query PubMed citations for the co-occurrence of AD with other diseases, using a list of 400 common pathologies.

Flavonoids-Macromolecules Interactions in Human Diseases with Focus on Alzheimer, Atherosclerosis and Cancer.

Flavonoids, a class of polyphenols, consumed daily in our diet, are associated with a reduced risk for oxidative stress (OS)-related chronic diseases, such as cardiovascular disease, neurodegenerative diseases, cancer, and inflammation. The involvement of flavonoids with OS-related chronic diseases have been traditionally attributed to their antioxidant activity. However, evidence from recent studies indicate that flavonoids' beneficial impact may be assigned to their interaction with cellular macromolecules, rather than exerting a direct antioxidant effect.

Galantamine Quantity and Alkaloid Profile in the Bulbs of and cultivars () Grown in Israel.

Alkaloids produced by the bulbs of the are a source of pharmaceutical compounds. The main alkaloid, galantamine, is a reversible acetylcholinesterase inhibitor and allosteric nicotinic receptor modulator, which slows cognitive and functional decline in mild to moderate dementia due to Alzheimer's disease. Having a complex stereochemistry, the organic synthesis of galantamine for pharmaceutical uses is highly challenging and not always economically viable, and it is therefore isolated from bulbs.

Lyso-diacylglyceryltrimethylhomoserine (lyso-DGTS) isolated from Nannochloropsis microalgae improves high-density lipoprotein (HDL) functions.

Many population studies have shown that blood concentrations of high-density lipoprotein (HDL) cholesterol are inversely correlated with risk of cardiovascular disease (CVD). However, in recent studies, increasing blood HDL cholesterol concentrations failed to reduce CVD events. On the other hand, studies suggest that improving HDL quality can be a more efficient tool for assessing atherosclerotic risk than simply measuring blood HDL cholesterol concentration.

Genome-wide localization of the polyphenol quercetin in human monocytes.

Background: Quercetin is a polyphenol of great interest given its antioxidant activity and involvement in the immune response. Although quercetin has been well studied at the molecular level as a gene regulator and an activator of specific cellular pathways, not much attention has been given to its mechanism of action at the genome-wide level. The present study aims to characterize quercetin's interaction with cellular DNA and to show its subsequent effect on downstream transcription.

Punicalagin Decreases Serum Glucose Levels and Increases PON1 Activity and HDL Anti-Inflammatory Values in Balb/c Mice Fed a High-Fat Diet.

Polyphenols are consumed daily in the human diet and are associated with reduced risk of a number of chronic diseases, including cancer, cardiovascular disease, and diabetes. Traditionally, the health benefits of polyphenols have been attributed to their antioxidant activity, but many studies might be hampered by oral administration and insignificant bioavailability. Rather than exerting a direct antioxidant effect, the mechanisms by which polyphenols express their beneficial effect seem to involve their interaction with proteins.

Lyso-DGTS lipid isolated from microalgae enhances PON1 activities in vitro and in vivo, increases PON1 penetration into macrophages and decreases cellular lipid accumulation.

High-density lipoprotein (HDL) plays an important role in preventing atherosclerosis. The antioxidant effect of HDL is mostly associated with paraoxonase 1 (PON1) activity. Increasing PON1 activity using nutrients might improve HDL function and quality and thus, decrease atherosclerotic risk.

Punicalagin Induces Serum Low-Density Lipoprotein Influx to Macrophages.

High levels of circulating low-density lipoprotein (LDL) are a primary initiating event in the development of atherosclerosis. Recently, the antiatherogenic effect of polyphenols has been shown to be exerted via a mechanism unrelated to their antioxidant capacity and to stem from their interaction with specific intracellular or plasma proteins. In this study, we investigated the interaction of the main polyphenol in pomegranate, punicalagin, with apolipoprotein B-100 (ApoB100) that surrounds LDL.

The effects and mechanism of flavonoid-rePON1 interactions. Structure-activity relationship study.

Flavonoids are plant phenolic secondary metabolites that are widely distributed in the human diet. These antioxidants have received much attention because of their neuroprotective, cardioprotective, and chemopreventive actions. While a major focus has been on the flavonoids' antioxidant properties, there is an emerging view that many of the potential health benefits of flavonoids and their in vivo metabolites are due to modulatory actions in cells through direct interactions with proteins, and not necessarily due to their antioxidant function.

Glabridin protects paraoxonase 1 from linoleic acid hydroperoxide inhibition via specific interaction: a fluorescence-quenching study.

The enzyme paraoxonase 1 (PON1) binds to high-density lipoprotein (HDL) and is responsible for many of HDL's antiatherogenic properties. We previously showed that recombinant PON1 is inhibited by linoleic acid hydroperoxide (LA-OOH) present in the lipid fraction of the human carotid plaque (LLE) via oxidation of the enzyme's Cys284 thiol. Here we explore the effect of glabridin, an isoflavan isolated from licorice root, on preventing LA-OOH's inhibitory effect on rePON1 using the tryptophan-fluorescence-quenching technique and modeling calculations.