The role of vitamin C in skin care and health

Background. The effect of vitamin C on the skin. The skin is a protective barrier against harmful factors from the external environment, which is due to its unique structure. The skin contains vitamin C in various concentrations depending on the individual layers. Skin keratinocytes have the capacity to accumulate high concentrations of vitamin C, which may reduce inflammation caused by excessive exposure to UV irradiation. Aim of the study. The aim of the study was to systematize knowledge about the topical use of vitamin C in the care or treatment of skin defects based on a literature review and to indicate potential benefits in damages related to the overproduction of reactive oxygen species (ROS) and the skin aging process. Materials and methods. The literature review was performed by searching scientific databases: PubMed and Google Scholar. The search for relevant articles on the role of vitamin C in the skin was carried out using the following keywords: “vitamin C", "ascorbic acid", "magnesium ascorbyl phosphate", "ascorbyl-6-palmitate", "skin", "photoprotection", "photoaging". In order to increase the efficiency of work, the authors developed a concept of the publication that included division into subchapters that were assigned to individual authors in order to avoid duplicating information while editing the manuscript. The described methodology allowed for obtaining reliable information. Results. Vitamin C protects the keratinocyte from apoptosis and increases cell survival. It acts as an antioxidant that plays an important role by stimulating collagen synthesis and assisting in antioxidant protection against UV-induced photodamage. Vitamin C also influences gene expression of antioxidant enzymes, the organisation and accumulation of phospholipids, and promotes the formation of the stratum corneum and the differentiation of the epithelial cells in general. The provision of vitamin C to the skin greatly assists wound healing and minimises raised scar formation. Vitamin C supplementation for nutritional purposes is also important and can be combined with topical application. The effect of the comprehensive action of vitamin C is to protect tissues against oxidative damage by removing free radicals that damage the most important structures of the body: cell membranes, DNA and proteins. Conclusions. The effectiveness of vitamin C affects the condition of the skin and the rate of its aging. This study contains examples of research methods for reconstructed human epidermis or keratinocytes, but the literature review shows that these models lack other skin components such as fibroblasts, Langerhans cells, melanocytes and hair follicles. The human skin model has been developed in laboratories and is currently limited by the lack of many critical biological and structural features of the skin. Engineering a human skin equipped with, among others, into immune cells and capable of generating all components, including appendages, is a major challenge. Therefore, further research is needed to elucidate the exact mechanisms of action of vitamin C using a human skin model that containing other skin components

Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM) may predispose to Alzheimer’s disease (AD). The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress. The diabetic state also contributes to increased acetylcholinesterase (AChE) activity, which is one of the factors leading to neurodegeneration in AD. The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE) and establish the type of inhibition. Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 μmol/mL, mixed type of inhibition) and seemed to be selective towards AChE since it presented low anti-BuChE activity. The tested metformin prodrugs inhibited cholinesterases (ChE) at nanomolar range and thus were more active than metformin or phenformin. The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC50 = 890 nmol/mL, noncompetitive inhibition) and BuChE (IC50 = 28 nmol/mL, mixed type inhibition), while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC50 = 184 nmol/mL). Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE. In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future

Anti-amyloid drug design

Conceptual visualization of drug design via complexation of amphipathic helices(in red) compatible with the distribution of hydrophobicity in the fibril and exposing a hydrophilic layer, which facilitates interaction with water. This idea in based on the analysis of stop signals in proteins with linear propagation present in their structure

Transcription factor NRF2 as a therapeutic target for chronic diseases: a systems medicine approach

Systems medicine has a mechanism-based rather than a symptom- or organ-based approach to disease and identifies therapeutic targets in a nonhypothesis-driven manner. In this work, we apply this to transcription factor nuclear factor (erythroid-derived 2)-like 2 (NRF2) by cross-validating its position in a protein-protein interaction network (the NRF2 interactome) functionally linked to cytoprotection in low-grade stress, chronic inflammation, metabolic alterations, and reactive oxygen species formation. Multiscale network analysis of these molecular profiles suggests alterations of NRF2 expression and activity as a common mechanism in a subnetwork of diseases (the NRF2 diseasome). This network joins apparently heterogeneous phenotypes such as autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer. Importantly, this approach matches and confirms in silico several applications for NRF2-modulating drugs validated in vivo at different phases of clinical development. Pharmacologically, their profile is as diverse as electrophilic dimethyl fumarate, synthetic triterpenoids like bardoxolone methyl and sulforaphane, protein-protein or DNA-protein interaction inhibitors, and even registered drugs such as metformin and statins, which activate NRF2 and may be repurposed for indications within the NRF2 cluster of disease phenotypes. Thus, NRF2 represents one of the first targets fully embraced by classic and systems medicine approaches to facilitate both drug development and drug repurposing by focusing on a set of disease phenotypes that appear to be mechanistically linked. The resulting NRF2 drugome may therefore rapidly advance several surprising clinical options for this subset of chronic diseases

The Influence of Selected Antipsychotic Drugs on Biochemical Aspects of Alzheimer’s Disease

The aim of this study was to assess the potency of selected antipsychotic drugs (haloperidol (HAL), bromperidol (BRMP), benperidol (BNP), penfluridol (PNF), pimozide (PIM), quetiapine (QUET) and promazine (PROM)) on the main pathological hallmarks of Alzheimer’s disease (AD). Binary mixtures of donepezil and antipsychotics produce an anti-BuChE effect, which was greater than either compound alone. The combination of rivastigmine and antipsychotic drugs (apart from PNF) enhanced AChE inhibition. The tested antipsychotics (excluding HAL and PNF) significantly reduce the early stage of Aβ aggregation. BRMP, PIM, QUET and PROM were found to substantially inhibit Aβ aggregation after a longer incubation time. A test of human erythrocytes hemolysis showed that short-term incubation of red blood cells (RBCs) with QUET resulted in decreased hemolysis. The antioxidative properties of antipsychotics were also proved in human umbilical vein endothelial cells (HUVEC); all tested drugs were found to significantly increase cell viability. In the case of astrocytes, BNP, PNF, PIM and PROM showed antioxidant potential

Metformin and its sulphonamide derivative simultaneously potentiateanti-cholinesterase activity of donepezil and inhibit beta-amyloid aggregation

The aim of this study was to assess in vitro the effects of sulphenamide and sulphonamide derivatives of metformin on the activity of human acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), establish the type of inhibition, and assess the potential synergism between biguanides and donepezil towards both cholinesterases (ChEs) and the effects on the β-amyloid aggregation. Sulphonamide 5 with para-trifluoromethyl- and ortho-nitro substituents in aromatic ring inhibited AChE in a mixed-type manner at micromolar concentrations (IC50 = 212.5 ± 48.3 µmol/L). The binary mixtures of donepezil and biguanides produce an anti-AChE effect, which was greater than either compound had alone. A combination of donepezil and sulphonamide 5 improved the IC50 value by 170 times. Compound 5 at 200 µmol/L inhibited Aβ aggregation by ∼20%. In conclusion, para-trifluoromethyl-ortho-nitro-benzenesulphonamide presents highly beneficial anti-AChE and anti-Aβ aggregation properties which could serve as a promising starting point for the design and development of novel biguanide-based candidates for AD treatment