A polyphenol-rich diet protects against chronic pathologies by modulating numerous physiological processes, such as cellular redox potential, enzymatic activity, cell proliferation and signaling transduction pathways. However, polyphenols have a low oral bioavailability mainly due to an extensive biotransformation mediated by phase I and phase II reactions in enterocytes and liver but also by gut microbiota. Despite low oral bioavailability, most polyphenols proved significant biological effects which brought into attention the low bioavailability/high bioactivity paradox. In recent years, polyphenol metabolites have attracted great interest as many of them showed similar or higher intrinsic biological effects in comparison to the parent compounds. There is a huge body of literature reporting on the biological functions of polyphenol metabolites generated by phase I and phase II metabolic reactions and gut microbiota-mediated biotransformation. In this respect, the review highlights the pharmacokinetic fate of the major dietary polyphenols (resveratrol, curcumin, quercetin, rutin, genistein, daidzein, ellagitannins, proanthocyanidins) in order to further address the efficacy of biometabolites as compared to parent molecules. The present work strongly supports the contribution of metabolites to the health benefits of polyphenols, thus offering a better perspective in understanding the role played by dietary polyphenols in human health.

Bioactivity of dietary polyphenols: The role of metabolites

Interest in antimicrobial gold complexes originated from the work of Robert Koch at the end of 19th century, who demonstrated that potassium dicyanidoaurate(I), K[Au(CN)2], showed activity against Mycobacterium tuberculosis, a causative agent of tuberculosis. Subsequently, a large number of gold(I) and gold(III) complexes have been evaluated as possible antimicrobial agents against a broad spectrum of bacteria, fungi and parasites. The first part of the present review article summarizes the results achieved in the field of antibacterial and antifungal activity of gold(I) and gold(III) complexes. The represented gold(I) complexes have been divided into three distinct classes based on the type of coordinated ligand: (i) complexes with phosphine-type ligands, (ii) complexes with N-heterocyclic carbene ligands and (iii) various other gold(I) complexes, while the results related to the antibacterial and antifungal gold(III) complexes have been mainly focused on the organometallic-type of complexes. The second section of this article represents findings obtained from the evaluation of antimalarial activity of gold complexes against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum parasite. Antimalarial gold(I) and gold(III) complexes have been divided into the following classes, based on the nature of the coordinated ligand: (i) complexes with chloroquine and its derivatives, (ii) complexes with N-heterocyclic carbene ligands, (iii) complexes containing functionalised alkynes and (iv) thiosemicarbazonato ligands, as well as (v) other gold(I) and gold(III) complexes. In the last section of the review, gold(I) and gold(III) complexes have been reported to be potential agents against parasites that cause amoebiasis, leishmaniasis and trypanosomiasis. A systematic summary of these results could contribute to the future design of new gold(I) and gold(III) complexes as potential antimicrobial agents.

Gold complexes as antimicrobial agents: an overview of different biological activities in relation to the oxidation state of the gold ion and the ligand structure

Curcumin, a plant-derived polyphenolic compound, naturally present in turmeric (Curcuma longa), has been the subject of intensive investigations on account of its various activities. The implementation of safe, beneficial and highly functional compounds from natural sources in human nutrition/prevention/therapy requires some modifications in order to achieve their multi-functionality, improve their bioavailability and delivery strategies, with the main aim to enhance their effectiveness. The low aqueous solubility of curcumin, its rapid metabolism and elimination from the body, and consequently, poor bioavailability, constitute major obstacles to its application. The main objectives of this review are related to reported strategies to overcome these limitations and, thereby, improve the solubility, stability and bioavailability of curcumin. The effectiveness of curcumin could be greatly improved by using nanoparticle-based carriers. The significance of the quality of a substance delivery system is reflected in the fact that carrying curcumin as a food additive/nutrition also means carrying the active biological product/drug. This review summarizes the state of the art, and highlights some examples and the most significant advances in the field of curcumin research.

Curcumin, a Compound from Natural Sources, a True Scientific Challenge – A Review

Type 2 diabetes mellitus (T2DM) is an ensemble of metabolic diseases that has reached pandemic dimensions all over the world. The multifactorial nature of the pathology makes patient management, which includes lifelong drug therapy and lifestyle modification, extremely challenging. It is well known that T2DM is a preventable disease, therefore lowering the incidence of new T2DM cases could be a key strategy to reduce the global impact of diabetes. Currently, there is growing evidence on the efficacy of the use of medicinal plants supplements for T2DM prevention and management. Among these medicinal plants, curcumin is gaining a growing interest in the scientific community. Curcumin is a bioactive molecule present in the rhizome of the Curcuma longa plant, also known as turmeric. Curcumin has different pharmacological and biological effects that have been described by both in vitro and in vivo studies, and include antioxidant, cardio-protective, anti-inflammatory, anti-microbial, nephro-protective, anti-neoplastic, hepato-protective, immunomodulatory, hypoglycaemic and anti-rheumatic effects. In animal models, curcumin extract delays diabetes development, improves β-cell functions, prevents β-cell death, and decreases insulin resistance. The present review focuses on pre-clinical and clinical trials on curcumin supplementation in T2DM and discusses the peculiar mechanisms by which curcumin might ameliorate diabetes management.

https://www.mdpi.com/2072-6643/11/8/1837/pdf

Curcumin and Type 2 Diabetes Mellitus: Prevention and Treatment

Development of native and modified banana starch nanoparticles as vehicles for curcumin.

Curcumin (CU) shows a wide range of pharmacological properties including antioxidant, anti-inflammatory, and antitumor effects. In order to understand the chemical basis of different activities of curcumin, we have studied the oxidation and reduction of curcumin. Based on cyclic and differential pulse voltammetric methods, using carbon paste and hanging mercury drop electrodes, in the present study we tested different parameters to optimize the conditions for the determination of curcumin and its electrochemical characteristics. Better results were obtained via differential pulse voltammetry using carbon paste electrode. Curcumin yields well-defined differential pulse voltammetric responses with well-defined oxidation (in the potential region of 0.3 - 0.6 V, vs. Ag/AgCl) and reduction (at 0.3 V) peaks using carbon paste electrode.

Electroanalytical Study of the Antioxidant and Antitumor Agent Curcumin

The development of chemical sensors has received widespread attention during the past two decades because of their extensive use in environmental monitoring and clinical analysis via rapid, accurate, reproducible, and low-cost methods. The data reported in literature demonstrate that carbon paste electrodes (CPEs) are very suitable for a variety of applications and many works have thus been devoted to developing new ion-selective electrodes based on carbon paste as the electrode material of choice. Chemically modified CPEs have frequently been employed as potentiometric sensors in trace analysis for metal ions, organic pollutants and biological substances. Most of these electrodes are operated via the ion-exchange process of the active component incorporated into the carbon paste matrix. This review article concentrates on such achievements in the context of the general development across the field.

Carbon paste electrodes in potentiometry: the state of the art and applications in modern electroanalysis (a review)

The 1H nuclear magnetic resonance spectroscopy was applied to study the reaction of the dipeptide glycyl-d,l-methionine (H-Gly-d,l-Met-OH) and its N-acetylated derivative (Ac-Gly-d,l-Met-OH) with hydrogen tetrachloridoaurate(III) (H[AuCl4]). The corresponding peptide and [AuCl4]– were reacted in 1:1, 2:1, and 3:1 molar ratios, and all reactions were performed at pD 2.45 in 0.01 M DCl as solvent and at 25°C. It was found that the first step of these reactions is coordination of Au(III) to the thioether sulfur atom with formation of the gold(III)-peptide complex [AuCl3(R-Gly-Met-OH-S)] (R=H or Ac). This intermediate gold(III) complex further reacts with an additional methionine residue to generate the R-Gly-Met-OH chlorosulfonium cation as the second intermediate product, which readily undergoes hydrolysis to give the corresponding sulfoxide. The oxidation of the methionine residue in the reaction between H-Gly-d,l-Met-OH and [AuCl4]– was five times faster (k
 2 = 0.363 ± 0.074 M-1s-1) in comparison to the same process with N-acetylated derivative of this peptide (k
 2 = 0.074 ± 0.007 M-1s-1). The difference in the oxidation rates between these two peptides can be attributed to the free terminal amino group of H-Gly-d,l-Met-OH dipeptide. The mechanism of this redox process is discussed and, for its clarification, the reaction of the H-Gly-d,l-Met-OH dipeptide with [AuCl4]– was additionally investigated by UV-Vis and cyclic voltammetry techniques. From these measurements, it was shown that the [AuCl2]– complex under these experimental conditions has a strong tendency to disproportionate, forming [AuCl4]– and metallic gold. This study contributes to a better understanding of the mechanism of the Au(III)-induced oxidation of methionine and methionine-containing peptides in relation to the severe toxicity of anti-arthritic and anticancer gold-based drugs.

/pdf/a-spectroscopic-and-electrochemical-investigation-of-the-48ui68mdul.pdf

A spectroscopic and electrochemical investigation of the oxidation pathway of glycyl- d,l -methionine and its N -acetyl derivative induced by gold(III)

Spectroscopic (1H NMR and UV–vis) and electrochemical (CV) techniques have been applied to study the reaction of Gly-Met dipeptide with [Au(en)Cl2]+ complex having bidentate coordinated ethylenediamine (en) ligand. The final product in the investigated reaction was Gly-Met sulfoxide, formed by the oxidation of methionine residue with [Au(en)Cl2]+. The formation of Gly-Met sulfoxide proceeds through two steps including the monodentate coordination of thioether sulfur atom of methionine residue and release of en ligand from Au(III). In order to investigate the influence of the pH and Cl− concentration on this redox process, the reaction was performed in solution of KCl with the concentration varying from 0.01 to 0.50 M and in the pH range 2.00–5.00. The obtained kinetic data showed that oxidation of methionine residue in Gly-Met was 200 times slower in comparison to the same process with previously investigated [AuCl4]− complex. Difference in the oxidation rate of Gly-Met between these two complexes was attributed to the presence of chelated ethylenediamine ligand in [Au(en)Cl2]+. The finding that the oxidation of sulfur-containing peptides and proteins can be inhibited by structural modifications of gold(III) complexes introducing polydentate nitrogen-containing ligands can contribute in designing new gold(III) complexes with lower toxic side effects.

/pdf/oxidation-of-methionine-residue-in-gly-met-dipeptide-induced-42ewxh6bbw.pdf

Zorka Stanić

Papers

Curcumin, a Compound from Natural Sources, a True Scientific Challenge – A Review

Electroanalytical Study of the Antioxidant and Antitumor Agent Curcumin

Carbon paste electrodes in potentiometry: the state of the art and applications in modern electroanalysis (a review)

A spectroscopic and electrochemical investigation of the oxidation pathway of glycyl- d,l -methionine and its N -acetyl derivative induced by gold(III)

Oxidation of methionine residue in Gly-Met dipeptide induced by [Au(en)Cl2]+ and influence of the chelated ligand on the rate of this redox process