Biological Membrane-Penetrating Peptides: Computational Prediction and Applications.

Peptides comprise a versatile class of biomolecules that present a unique chemical space with diverse physicochemical and structural properties. Some classes of peptides are able to naturally cross the biological membranes, such as cell membrane and blood-brain barrier (BBB). Cell-penetrating peptides (CPPs) and blood-brain barrier-penetrating peptides (B3PPs) have been explored by the biotechnological and pharmaceutical industries to develop new therapeutic molecules and carrier systems. The computational prediction of peptides' penetration into biological membranes has been emerged as an interesting strategy due to their high throughput and low-cost screening of large chemical libraries. Structure- and sequence-based information of peptides, as well as atomistic biophysical models, have been explored in computer-assisted discovery strategies to classify and identify new structures with pharmacokinetic properties related to the translocation through biomembranes. Computational strategies to predict the permeability into biomembranes include cheminformatic filters, molecular dynamics simulations, artificial intelligence algorithms, and statistical models, and the choice of the most adequate method depends on the purposes of the computational investigation. Here, we exhibit and discuss some principles and applications of these computational methods widely used to predict the permeability of peptides into biomembranes, exhibiting some of their pharmaceutical and biotechnological applications.

Synthesis, Characterization, Applications, and Toxicity of Green Synthesized Nanoparticles.

Nanotechnology is a cutting-edge area with numerous industrial applications. Nanoparticles are structures that have dimensions ranging from 1 - 100 nm, which significantly exhibit different mechanical, optical, electrical, and chemical properties when compared with their larger counterparts. Synthetic routes that use natural sources, such as plant extracts, honey, and microorganisms, are environmentally friendly and low-cost methods that can be used to obtain nanoparticles. These methods of synthesis generate products that are more stable and less toxic than those obtained using conventional methods. Nanoparticles formed by titanium dioxide, zinc oxide, silver, gold, and copper, as well as cellulose nanocrystals, are among the nanostructures obtained by green synthesis that have shown interesting applications in several technological industries. Several analytical techniques have also been used to analyze the size, morphology, hydrodynamics, diameter, and chemical functional groups involved in the stabilization of the nanoparticles as well as to quantify and evaluate their formation. Despite their pharmaceutical, biotechnological, cosmetic, and food applications, studies have detected their harmful effects on human health and the environment, and thus, caution must be taken in uses involving living organisms. The present review aims to present an overview of the applications, the structural properties, and the green synthesis methods that are used to obtain nanoparticles, and special attention is given to those obtained from metal ions. The review also presents the analytical methods used to analyze, quantify, and characterize these nanostructures.

Bioactive Natural Compounds and Antioxidant Activity of Essential Oils from Spice Plants: New Findings and Potential Applications.

Spice plants have a great influence on world history. For centuries, different civilizations have used them to condiment the foods of kings and nobles and applied them as embalming preservatives, perfumes, cosmetics, and medicines in different regions of the world. In general, these plants have formed the basis of traditional medicine and some of their derived substances have been utilized to treat different human diseases. Essential oils (EOs) obtained from these plants have been also used as therapeutic agents and have shown supportive uses in remedial practices. The discovery and development of bioactive compounds from these natural products, based on their traditional uses, play an important role in developing the scientific evidence of their potential pharmaceutical, cosmetic, and food applications. In the present review, using recent studies, we exhibit a general overview of the main aspects related to the importance of spice plants widely used in traditional medicine: Cinnamomumzeylanicum (true cinnamon), Menthapiperita (peppermint), Ocimumbasilicum (basil), Origanumvulgare (oregano), Piper nigrum (black pepper), Rosmarinus officinalis (rosemary), and Thymus vulgaris (thyme); and we discuss new findings of the bioactive compounds obtained from their EOs, their potential applications, as well as their molecular mechanisms of action, focusing on their antioxidant activity. We also exhibit the main in vitro methods applied to determine the antioxidant activities of these natural products.

Antioxidant activity and physicochemical characteristics of honeys from the eastern Amazon region, Brazil / Atividade antioxidante e características físico-químicas de méis da Amazônia Oriental, Brasil / Antioxidant activity and physicochemical characteristics of honeys from the eastern Amazon region, Brazil

RESUMO O mel é um produto natural que apresenta várias propriedades benéficas para a saúde, tais como atividade antinflamatória, antioxidante e antimicrobiana, as quais dependem de sua composição. Neste contexto, as propriedades físico-químicas (cor, pH, conteúdo de cinzas, umidade, açúcares e compostos fenólicos totais) e a atividade antioxidadente (capacidade de remoção do radical DPPH) de méis de abelhas Apis mellifera de Santarém, na principal região de produção de mel na Amazônia Oriental, Brasil, foram avaliadas. A maioria das amostras teve cor escura e apresentaram-se ácidas. Os teores de cinzas e a umidade variaram de 0,112 a 0,318 e de 14,751 a 17,514, respectivamente. O teor de açúcares redutores vairou entre 62,873 e 91,563%. O teor total de compostos fenólicos foi mais elevado que os já reportados na literatura, variando entre 15,22 e 16,51 mg g−1 e 17,70 e 18,94 mg g−1 para amostras de mel protegidas e expostas à radiação UV, respectivamente. A quercetina foi encontrada apenas no mel que foi protegido da luz, com teores variando entre 0,24 e 0,43 mg g−1. A ausência de quercetina nas amostras de mel expostas à luz sugere que a radiação UV pode ter degradado esse composto. Todas as amostras apresentaram máxima capacidade de remover o radical DPPH próxima a 50%. Houve correlação inversa entre a cor e o pH, cinzas, açúcares redutores e teor de umidade, e correlação positiva entre a cor e o teor de composto fenólicos e a atividade antioxidante.

ABSTRACT Honey is a natural product that has several beneficial properties for health, such as anti-inflammatory, antioxidant and antimicrobial activities, which depend on its composition. In this context, physicochemical properties (colour, pH, ash, moisture, sugars, and total phenolic contents) and antioxidant activity (DPPH radical scavenging ability) of Apis mellifera honeys from Santarém, the main honey production area in the eastern Amazon region, were evaluated. Most samples were dark in colour and acidic. The ash and moisture contents ranged from 0.112 to 0.318 and from 14.751 to 17.514, respectively. The reducing sugars content was 62.873-91.563%. The total amount of phenolic compounds was higher than normally reported, ranging between 15.22 and 16.51 mg g−1 and 17.70 and 18.94 mg g−1, for honey after and before exposure to light, respectively. Quercetin was found only in honey that had been protected from light, with values ranging from 0.24 to 0.43 mg g-1. The absence of quercetin in the samples of honey exposed to light suggests that UV radiation has degraded this compound. All samples presented maximum radical scavenging capacity close to 50%. Our results showed inverse correlations between the colour and pH, ash, reducing sugars, and moisture content, and positive correlations between the colour and the concentration of phenolic compounds, and antioxidant activity.

Diphenyl diselenide decreases serum levels of total cholesterol and tissue oxidative stress in cholesterol-fed rabbits.

Hypercholesterolaemia and oxidative stress are well-known risk factors in coronary artery diseases. Diphenyl diselenide is a synthetic organoselenium compound that has been shown to have in vitro and in vivo antioxidant properties. In this study, we investigated whether diphenyl diselenide could reduce the hypercholesterolaemia and diminish the tissue oxidative stress in cholesterol-fed rabbits. Twenty-four New Zealand white male rabbits were randomly divided into four groups. Each group was fed a different diet as follows: Control group--regular chow; Cholesterol group--1% cholesterol-enriched diet; diphenyl diselenide group--regular diet supplemented with 10 ppm diphenyl diselenide; and Chol/diphenyl diselenide group--the same cholesterol-rich supplemented with 10 ppm diphenyl diselenide. After 45 days of treatment, the rabbits were killed and the blood, liver, and brain were used for laboratory analysis. The results showed that the serum levels of total cholesterol were markedly increased in cholesterol-fed rabbits and the consumption of diphenyl diselenide decreased these levels approximately twofold in Chol/diphenyl diselenide rabbits (P < 0.05). The intake of diphenyl diselenide by hypercholesterolaemic rabbits diminished the serum and hepatic thiobarbituric acid reactive substances levels as well as the production of reactive oxygen species in the blood and brain (P < 0.05) when compared to the cholesterol group. In addition, diphenyl diselenide supplementation increased hepatic and cerebral delta-aminolevulinic dehydratase activity and hepatic non-protein thiol groups levels despite hypercholesterolaemia (P < 0.05). In summary, the results showed that diphenyl diselenide reduced the hypercholesterolaemia and the oxidative stress in cholesterol-fed rabbits.

Enhancement of iron-catalyzed lipid peroxidation by acidosis in brain homogenate: comparative effect of diphenyl diselenide and ebselen.

Iron is more soluble at lower pH values; therefore we hypothesized that decreasing the environmental pH would lead to increased iron-mediated lipid peroxidation. Diphenyl diselenide and ebselen are potential candidates as neuroprotective agent, particularly in situations involving overproduction of free radicals and involving cellular pH fall. The aim of the present study was (a) to investigate the relationship between lipid peroxidation and acidosis in brain homogenate and (b) to test the influence of pH on the antioxidant properties of diphenyl diselenide and ebselen. For the purpose rat brain homogenate was incubated at different pH ranging from physiological to acidic values and extent of lipid peroxidation was measured. Thiobarbituric acid-reactive species (TBARS) production significantly increased when homogenate was incubated in the pH (5.4-6.8) medium both in the absence and presence of Fe (II) as compared with physiological pH (7.4). These data indicate that lipid peroxidation processes, mediated by iron, are enhanced with decreasing extracellular pH. The iron mobilized may come from reserves where it is weakly bound. Diphenyl diselenide significantly protected TBARS production at all studied pH values while ebselen offered only a small statistically non-significant protection. However, calculated IC(50) for TBARS inhibition indicated that pH did not change anti-oxidant activities of the tested compounds. This study provides in-vitro evidence for acidosis induced oxidative stress in brain homogenate and anti-oxidant action of diphenyl diselenide.