Current Pharmaceutical Design - Volume 25, Issue 15, 2019

Chronic and non-healing wounds, especially diabetic foot ulcers and radiation injuries, imply remarkable morbidity with a significant effect on the quality of life and a high sanitary cost. The management of these wounds requires complex actions such as surgical debris, antibiotic treatment, dressings and even revascularization. These wounds are characterized by poor oxygen supply resulting in inadequate oxygenation of the affected tissue. The adjuvant treatment with hyperbaric oxygen therapy (HBOT) may increase tissue oxygenation favoring the healing of wounds which do not respond to the usual clinical care. The increase in the partial pressure of oxygen contributes to cover the energy demands necessary for the healing process and reduces the incidence of infections. Moreover, the increase in oxygen leads to the production of reactive species with hormetic activity, acting on signaling pathways that modulate the synthesis of inflammation mediators, antioxidants and growth factors which can contribute to the healing process. Studies performed with cell cultures and in animal models seem to demonstrate the beneficial effects of HBOT. However, clinical trials do not show such conclusive results; thus, additional randomized placebo-controlled studies are necessary to determine the real efficacy of HBOT and the mechanism of action for various types of wounds.

Background: Selenium (Se) is a trace element active in selenoproteins, which can regulate oxidative stress. It is generally perceived as an import factor for maintaining health in the elderly. Methods: The goal of this review is to discuss selenium concentration in biological samples, primarily serum or plasma, as a function of age and its relation with longevity. The elemental level in various age-related diseases is reviewed. Conclusion: Highest selenium values were observed in healthy adults, while in an elderly population significantly lower concentrations were reported. Variables responsible for contradictory findings are mentioned. Risk and benefits of Se-supplementation still remain under debate.

Selenium is an essential non-metal trace element, and the imbalance in the bioavailability of selenium is associated with many diseases ranking from acute respiratory distress syndrome, myocardial infarction and renal failure (Se overloading) to diseases associated with chronic inflammation like inflammatory bowel diseases, rheumatoid arthritis, and atherosclerosis (Se unload). The only source of selenium is the diet (animal and cereal sources) and its intestinal absorption is limiting for selenocysteine and selenomethionine synthesis and incorporation in selenoproteins. In this review, after establishing the link between selenium and inflammatory diseases, we envisaged the potential of selenium nanoparticles and organic selenocompounds to compensate the deficit of selenium intake from the diet. With high selenium loading, nanoparticles offer a low dosage to restore selenium bioavailability whereas organic selenocompounds can play a role in the modulation of their antioxidant or antiinflammatory activities.

There is growing evidence that cancer chemoprevention employing natural, bioactive compounds may halt or at least slow down the different stages of carcinogenesis. A particularly advantageous effect is attributed to derivatives of sulfur-organic phytochemicals, such as glucosinolates (GLs) synthesized mainly in Brassicaceae plant family. GLs are hydrolysed enzymatically to bioactive isothiocyanates (ITC) and indoles, which exhibit strong anti-inflammatory and anti-carcinogenic activity. Highly bioavailable electrophilic ITC are of particular interest, as they can react with nucleophilic groups of important biomolecules to form dithiocarbamates, thiocarbamates and thioureas. These modifications seem responsible for the chemopreventive activity, but also for genotoxicity and mutagenicity. It was documented that ITC can permanently bind to important biomolecules such as glutathione, cytoskeleton proteins, transcription factors NF-ΚB and Nrf2, thiol-disulfide oxidoreductases, proteasome proteins or heat shock proteins. Furthermore, ITC may also affect epigenetic regulation of gene expression, e.g. by inhibition of histone deacetylases. Some other derivatives of glucosinolates, especially indoles, are able to form covalent bonds with nucleobases in DNA, which may result in genotoxicity and mutagenicity. This article summarizes the current state of knowledge about glucosinolates and their degradation products in terms of possible interactions with reactive groups of cellular molecules.

Background: Many of the activities associated with pepper fruits have been attributed to piperine, the most active compound present in these spices. Objective: This paper aims to provide an overview of the known properties of piperine, i.e. piperine’s chemistry, its physiological activity, documented interactions as a bioenhancer and reported data concerning its toxicity, antioxidant properties and anticancer activity. Discussion: It is known that piperine possesses several properties. In its interaction with other drugs, it can act as a bioavailability enhancer; this effect is also manifested in combination with other nutraceuticals, e.g. with curcumin, i.e. piperine can modify curcumin’s antioxidant, anti-inflammatory, antimicrobial and anticancer effects. Piperine displays significant immunomodulating, antioxidant, chemopreventive and anticancer activity; these effects have been shown to be dose-dependent and tissue-specific. However, the main limitation associated with piperine seems to be its low bioavailability, a disadvantage that innovative formulations are overcoming. Conclusion: It is predicted that an increasing number of studies will focus on piperine, especially those directed towards unraveling its properties at molecular level. The current knowledge about the action of piperine will form a foundation for ways to improve piperine’s bioavailability e.g. exploitation of different carrier systems. The therapeutical applications of this compound will be clarified, and piperine will be recognized as an important nutraceutical.

Background: At sufficient sun exposure, humans can synthesize vitamin D3 endogenously in their skin, but today’s lifestyle makes the secosteroid a true vitamin that needs to be taken up by diet or supplementation with pills. The vitamin D3 metabolite 1α,25-dihydroxyvitamin D3 acts as a nuclear hormone activating the transcription factor vitamin D receptor (VDR). Methods: This review discusses the biological effects of micronutrient vitamin D ranging from calcium homeostasis and bone formation to the modulation of innate and adaptive immunity. Results: Since normal human diet is sufficient in vitamin D, the need for efficient vitamin D3 synthesis in the skin acts as an evolutionary driver for its lightening during the migration out of Africa towards North. Via activating the VDR, vitamin D has direct effects on the epigenome and the expression of more than 1000 genes in most human tissues and cell types. Conclusions: The pleiotropic action of vitamin D in health and disease prevention is explained through complex gene regulatory events of the transcription factor VDR.

Background: Fish is consumed as food worldwide and is considered as a rich source of essential nutrients required for a healthy life. Supplementation with fish oil has been adopted as a solution to prevent or cure many pathophysiological states and diseases by both the professionals and the civil population. The beneficial effects are, however, being questioned, as some controversial results were obtained in clinical and population studies. Methods: Critical evaluation of studies regarding known effects of fish oil, both in favour of its consumption and related controversies. Results: From the literature review, contradictory allegations about the positive action of the fish oil on human health emerged, so that a clear line about its beneficial effect cannot be withdrawn. Conclusion: Scientific results on the application of fish oil should be taken with caution as there is still no standardised approach in testing its effects and there are significantly different baselines in respect to nutritional and other lifestyle habits of different populations.

Background: The Mediterranean diet is a healthy eating pattern that protects against the development of Type 2 diabetes mellitus (T2DM), a metabolic disease characterized by elevated blood sugar levels due to pancreatic beta-cell functional impairment and insulin resistance in various tissues. Inspired by the ancient communities, this diet emphasizes eating primarily plant-based foods, including vegetables, legumes, fruits, cereals, and nuts. Importantly, virgin olive oil is used as the principal source of fat. Red meat is consumed in low amounts while wine and fish are consumed moderately. Objective: Here, we review the most beneficial components of the Mediterranean Diet and tentative mechanisms of action for prevention and/or management of T2DM, based on research conducted within the last decade. Methods: The references over the last five years have been reviewed and they have been selected properly according to inclusion/ exclusion criteria. Results: Several bioactive diet components were evaluated to prevent inflammation and cytokine-induced oxidative damage, reduce glucose concentration, carbohydrate absorption and increase insulin sensitivity and related gene expression. Conclusion: The adherence to a healthy lifestyle, including diet, exercise and habits remains the best approach for the prevention of diabetes as well as frequent check-ups and education. Though diabetes has a strong genetic component, in recent years many reports strongly point to the critical role of lifestyle specific epigenetic modifications in the development of T2DM. It remains to be established how different components of the Mediterranean Diet interact and influence the epigenetic landscape to prevent or treat the disease.

Background: Several drugs have been currently approved for the treatment of obesity. The pharmacokinetic of liraglutide, as well as the treatment of type 2 diabetes mellitus, have been widely described. Objective: To analyze the published systematic reviews on the use of liraglutide for the treatment of obesity. Methods: Systematic reviews were found out through MEDLINE searches, through EBSCO host and the Cochrane Library based on the following terms: "liraglutide" as major term and using the following Medical Subject Headings (MesH) terms: "obesity", "overweight", "weight loss". A total of 3 systematic reviews were finally included to be analyzed. Results: From the three systematic reviews selected, only two included the randomized clinical trials, while the third study reviewed both randomized and non-randomized clinical trials. Only one review performed statistical tests of heterogeneity and a meta-analysis, combining the results of individual studies. Another review showed the results of individual studies with odds ratio and confidence interval, but a second one just showed the means and confidence intervals. In all studies, weight loss was registered in persons treated with liraglutide in a dose dependent form, reaching a plateau at 3.0 mg dose, which was reached just in men. Most usual adverse events were gastrointestinal. Conclusion: More powerful and prospective studies are needed to assess all aspects related to liraglutide in the overweight and obesity treatment.

Background: The effects of vegetable oils on human health depend on their components. Therefore, their profiles of lipid nutrients and polyphenols were determined. Objective: To establish and compare the fatty acid, tocopherol, phytosterol and polyphenol profiles of Mediterranean oils: cosmetic and dietary argan oils (AO; Morocco: Agadir, Berkane); olive oils (OO; Morocco, Spain, Tunisia); milk thistle seed oils (MTSO; Tunisia: Bizerte, Sousse, Zaghouane); nigella seed oil (NSO). Methods: The biochemical profiles were determined by gas chromatography-flame ionization, high performance liquid chromatography and gas chromatography, coupled with mass spectrometry as required. The antioxidant and cytoprotective activities were evaluated with the KRL (Kit Radicaux Libres) and the fluorescein diacetate tests on nerve cells treated with 7-ketocholesterol (7KC). Results: The fatty acid profile revealed high linoleic acid (C18:2 n-6) content in AO, OO, MTSO and NSO. The highest levels of oleic acid (C18:1 n-9) were found in AO and OO. The tocopherol profile showed that Agadir AO contained the highest amount of α-tocopherol, also present at high level in MTSO and Tunisian OO; Berkane AO was rich in γ-tocopherol. The phytosterol profile indicated that β-sitosterol was predominant in the oils, except AO; spinasterol was only present in AO. Polyphenol profiles underlined that OO was the richest in polyphenols; hydroxytyrosol was only found in OO; few polyphenols were detected in AO. The oils studied have antioxidant activities, and all of them, except NSO, prevented 7KC-induced cell death. The antioxidant characteristics of AO were positively correlated with procatechic acid and compestanol levels. Conclusion: Based on their biochemical profiles, antioxidant and cytoprotective characteristics, AO, OO, and MTSO are potentially beneficial to human health.