First-in-Class Selenium-Containing Potent Serotonin Receptor 5-HT6 Agents with a Beneficial Neuroprotective Profile against Alzheimer's Disease.

Alzheimer's disease (AD) has a complex and not-fully-understood etiology. Recently, the serotonin receptor 5-HT6 emerged as a promising target for AD treatment; thus, here a new series of 5-HT6R ligands with a 1,3,5-triazine core and selenoether linkers was explored. Among them, the 2-naphthyl derivatives exhibited strong 5-HT6R affinity and selectivity over 5-HT1AR (13-15), 5-HT7R (14 and 15), and 5-HT2AR (13). Compound 15 displayed high selectivity for 5-HT6R over other central nervous system receptors and exhibited low risk of cardio-, hepato-, and nephrotoxicity and no mutagenicity, indicating its "drug-like" potential. Compound 15 also demonstrated neuroprotection against rotenone-induced neurotoxicity as well as antioxidant and glutathione peroxidase (GPx)-like activity and regulated antioxidant and pro-inflammatory genes and NRF2 nuclear translocation. In rats, 15 showed satisfying pharmacokinetics, penetrated the blood-brain barrier, reversed MK-801-induced memory impairment, and exhibited anxiolytic-like properties. 15's neuroprotective and procognitive-like effects, stronger than those of the approved drug donepezil, may pave the way for the use of selenotriazines to inhibit both causes and symptoms in AD therapy.

Quality Control of the Dietary Supplements Containing Selected Fat-Soluble Vitamins D and K.

Nowadays, the most important aspect related to the use of dietary supplements seems to be their quality. There are many reports indicating their insufficient quality primarily related to a much lower content of ingredients or even their absence. Currently, there is an increasing interest in supplementing the diet with various kinds of supplements, including those containing combinations of vitamins and minerals, among which preparations with vitamin D are very popular. This is probably due to the reduced production of this vitamin, depending on the amount of time spent in the sun and the use of UV-filters. Very often, preparations with cholecalciferol also contain vitamin K2, which is associated with their synergistic effect. Therefore, the question arises about the effectiveness of supplementation, which may be correlated with the quality of commonly available dietary supplements. In the presented work, it was undertaken to develop optimal conditions for the qualitative and quantitative determination of vitamins D2, D3 and K2 in dietary supplements available in various forms, using thin-layer chromatography with densitometric detection. As a result, the methodology for analyzing the content of three vitamins from various matrices was developed, optimized and validated in accordance with ICH requirements. The obtained results allow us to conclude that it is reliable and meets the requirements for analytical procedures used in the analysis of medicinal products. Based on the results obtained for examined dietary supplements, it can be stated that the amount of vitamin D3 in analyzed products is basically similar to that declared by the manufacturer, in contrast to vitamin K2, the content of which is diverse. The developed methodology seems to be a good, low-cost and quick way to control the quality of dietary supplements so that they can supplement the human diet and be a wholesome product.

Vitamin D - current stage of knowledge about analysis and supplementation.

Nowadays, topics related to the proper nutrition of the body, which requires a complex of compounds and supplementation of these ingredients have undoubtedly gained popularity, so it should come as no surprise that there is a widespread interest in vitamin D in science, medicine, analytics and nutrition. In the world of developing technologies, new directions of physiological action of this vitamin on the body are being discovered. Issues related to the demand for vitamin D in various populations and its sources in food, the appropriate form of supplementation, safety and toxicity are extremely important. The present manuscript focuses on the concise evaluation of key data in the field of vitamin D. Structure and physicochemical properties, demand and delivery trails, deficiency and its diagnosis, supplementation, interactions of vitamin D with supplements and drugs are discussed. Attention has also been paid to the methods of vitamin D analysis in various matrices, which allow for an accurate and precise quality assessment of dietary supplements, drugs and food products. The presented information allows deeper understanding of the mechanisms responsible for the development of many diseases in the context of vitamin D levels.

Analytical approaches to determination of carnitine in biological materials, foods and dietary supplements.

l-Carnitine is a vitamin-like amino acid derivative, which is an essential factor in fatty acid metabolism as acyltransferase cofactor and in energy production processes, such as interconversion in the mechanisms of regulation of cetogenesis and termogenesis, and it is also used in the therapy of primary and secondary deficiency, and in other diseases. The determination of carnitine and acyl-carnitines can provide important information about inherited or acquired metabolic disorders, and for monitoring the biochemical effect of carnitine therapy. The endogenous carnitine pool in humans is maintained by biosynthesis and absorption of carnitine from the diet. Carnitine has one asymmetric carbon giving two stereoisomers d and l, but only the l form has a biological positive effect, thus chiral recognition of l-carnitine enantiomers is extremely important in biological, chemical and pharmaceutical sciences. In order to get more insight into carnitine metabolism and synthesis, a sensitive analysis for the determination of the concentration of free carnitine, carnitine esters and the carnitine precursors is required. Carnitine has been investigated in many biochemical, pharmacokinetic, metabolic and toxicokinetic studies and thus many analytical methods have been developed and published for the determination of carnitine in foods, dietary supplements, pharmaceutical formulations, biological tissues and body fluid. The analytical procedures presented in this review have been validated in terms of basic parameters (linearity, limit of detection, limit of quantitation, sensitivity, accuracy, and precision). This article presented the impact of different analytical techniques, and provides an overview of applications that address a diverse array of pharmaceutical and biological questions and samples.

Bioactive substances of garlic and their role in dietoprophylaxis and dietotherapy.

Garlic is characterised by medicinal properties due to the content of over 2000 biologically active substances. Numerous commercially processed garlic forms, which differ in the content of bioactive compounds, especially sulphuric, are available on the market. The knowledge of the types of bioactive substances present in garlic and its products, their changes during treatment and pro-health influence is of crucial importance to the diet supplement producers, doctors, pharmacists and consumers. Therefore, this work has aimed to characterise the most important bioactive substances of garlic, its preparations and describe in detail the role of garlic in dietoprophylaxis and dietotherapy.