The comparison of antioxidant properties and nutrigenomic redox-related activities of vitamin C, C-vitamers, and other common ascorbic acid derivatives.

The term 'vitamin C' describes a group of compounds with antiscorbutic activity of l-ascorbic acid (AA). Despite AA's omnipresence in plant-derived foods, its derivatives have also been successfully implemented in the food industry as antioxidants, including the D-isomers, which lack vitamin C activity. This study aimed to determine the relationship between redox-related activities for five derivatives of AA using electrochemical, chemical, and biological approaches. Here we report that AA, C-vitamers, and other commonly consumed AA derivatives differ in their redox-related activities. As long as the physiological range of concentrations was maintained, there was no simple relationship between their redox properties and biological activity. Clear distinctions in antioxidant activity were observed mostly at high concentrations, which were strongly correlated with electrochemical and kinetic parameters describing redox-related properties of the studied compounds. Despite obvious similarities in chemical structures and antioxidant activity, we showed that C-vitamers may exhibit different nutrigenomic effects. Together, our findings provide a deeper insight into so far underinvestigated area combining chemical properties with biological activities of commonly applied AA derivatives.

Beyond Antioxidant Activity: Redox Properties of Catechins May Affect Changes in the DNA Methylation Profile-The Example of SRXN1 Gene.

The role of catechins in the epigenetic regulation of gene expression has been widely studied; however, if and how this phenomenon relates to the redox properties of these polyphenols remains unknown. Our earlier study demonstrated that exposure of the human colon adenocarcinoma HT29 cell line to these antioxidants affects the expression of redox-related genes. In particular, treatment with (-)-epigallocatechin (EGC) downregulated transcription of gene encoding sulfiredoxin-1 (SRXN1), the peroxidase involved in the protection of cells against hydrogen peroxide-induced oxidative stress. The aim of this study was to investigate whether the observed SRXN1 downregulation was accompanied by changes in the DNA methylation level of its promoter and, if so, whether it was correlated with the redox properties of catechins. The impact on DNA methylation profile in HT29 cells treated with different concentrations of five catechins, varying in chemical structures and standard reduction potentials as well as susceptibility to oxidation, was monitored by a methylation-sensitive high-resolution melting technique employing the SRXN1 promoter region as a model target. We demonstrated that catechins, indeed, are able to modulate DNA methylation of the SRXN1 gene in a redox-related manner. The nonlinear method in the statistical analysis made it possible to fish out two parameters (charge transfer in oxidation process Qox and time of electron transfer t), whose strong interactions correlated with observed modulation of DNA methylation by catechins. Based on these findings, we present a proof-of-concept that DNA methylation, which limits SRXN1 expression and thus restricts the multidirectional antioxidant action of SRXN1, may represent a mechanism protecting cells against reductive stress caused by particularly fast-reacting reductants such as EGC and (-)-epicatechin gallate (ECG) in our study.

Anti-cancer effect of Rumex obtusifolius in combination with arginase/nitric oxide synthase inhibitors via downregulation of oxidative stress, inflammation, and polyamine synthesis.

Cancer continues to be a leading cause of death worldwide, making the development of new treatment methods crucial in the fight against it. With cancer incidence rates increasing worldwide, ongoing research must focus on identifying new and effective ways to prevent and treat the disease. The combination of herbal extracts with chemotherapeutic agents has gained much interest as a novel strategy to combat cancer. Rumex obtusifolius L. is a wild plant known for its medicinal properties and is widely distributed worldwide. Our preclinical evaluations suggested that R. obtusifolius seed extracts possessed cancer-inhibiting properties and we also evaluated the beneficial effects of the arginase inhibitor NG-hydroxy-nor-L-arginine and nitric oxide inhibitor NG-nitro-L-arginine methyl ester in the treatment of breast cancer. The current study aimed to combine these observations and evaluate the antioxidant and antitumor properties of R. obtusifolius extracts alone and in combination with the arginase and nitric oxide synthase inhibitors. Metabolic characterization of the plant extract using a liquid chromatography/high-resolution mass spectrometry advanced system revealed the presence of 240 phenolic compounds many of which possess anticancer properties, according to the literature. In vitro studies revealed a significant cytotoxic effect of the R. obtusifolius extracts on the human colon (HT29) and breast cancer (MCF-7) cell lines. Thus, a new treatment approach of combining R. obtusifolius bioactive phytochemicals with the arginase and nitric oxide synthase inhibitors NG-nitro-L-arginine methyl ester and/or NG-hydroxy-nor-L-arginine, respectively, was proposed and could potentially be an effective way to treat breast cancer. Indeed, these combinations showed immunostimulatory, antiproliferative, antioxidant, anti-inflammatory, and antiangiogenic properties in a rat breast cancer model.

More than Just Antioxidants: Redox-Active Components and Mechanisms Shaping Redox Signalling Network.

The concept of oxidative stress as a condition underlying a multitude of human diseases has led to immense interest in the search for antioxidant-based remedies. The simple and intuitive story of "the bad" reactive oxygen species (ROS) and "the good" antioxidants quickly (and unsurprisingly) lead to the commercial success of products tagged "beneficial to health" based solely on the presence of antioxidants. The commercial success of antioxidants by far preceded the research aimed at understanding the exact redox-related mechanisms that are in control of shaping the states of health and disease. This review describes the redox network formed by the interplay of ROS with cellular molecules and the resulting regulation of processes at the genomic and proteomic levels. Key players of this network are presented, both involved in redox signalling and control of cellular metabolism linked to most, if not all, physiological processes. In particular, this review focuses on the concept of reductive stress, which still remains less well-established compared to oxidative stress.