Protective Role of Melatonin and Its Metabolites in Skin Aging

The skin, being the largest organ in the human body, is exposed to the environment and suffers from both intrinsic and extrinsic aging factors. The skin aging process is characterized by several clinical features such as wrinkling, loss of elasticity, and rough-textured appearance. This complex process is accompanied with phenotypic and functional changes in cutaneous and immune cells, as well as structural and functional disturbances in extracellular matrix components such as collagens and elastin. Because skin health is considered one of the principal factors representing overall “well-being” and the perception of “health” in humans, several anti-aging strategies have recently been developed. Thus, while the fundamental mechanisms regarding skin aging are known, new substances should be considered for introduction into dermatological treatments. Herein, we describe melatonin and its metabolites as potential “aging neutralizers”. Melatonin, an evolutionarily ancient derivative of serotonin with hormonal properties, is the main neuroendocrine secretory product of the pineal gland. It regulates circadian rhythmicity and also exerts anti-oxidative, anti-inflammatory, immunomodulatory, and anti-tumor capacities. The intention of this review is to summarize changes within skin aging, research advances on the molecular mechanisms leading to these changes, and the impact of the melatoninergic anti-oxidative system controlled by melatonin and its metabolites, targeting the prevention or reversal of skin aging.     

In Vitro Evaluation of Anti-Inflammatory and Protective Potential of an Extract from Cornus mas L. Fruit against H2O2-Induced Oxidative Stress in Human Skin Keratinocytes and Fibroblasts

Cornus mas L. is a rich source of valuable compounds with pro-health properties and, therefore, may be attractive for the pharmaceutical and cosmetic industry. This paper attempts to assess the antioxidant, anti-inflammatory, and protective effect of an extract from C. mas fruit on skin cells in vitro. The phytochemical analysis of the extract was carried out using UPLC-MS and the content of the main components was determined. The biological activity of the extract was assessed by in vitro analysis using two human cell lines: keratinocytes (HaCaT) and fibroblasts (BJ). Additionally, the ability of this extract to regulate gene expression (SOD-1, Nox-4) in skin cells was evaluated. Moreover, the impact of the extract and its main components, including loganic acid and cornuside, on the level of inflammatory cytokines in H₂O₂-treated cells was assessed. The tests showed that the extract has strong antioxidant properties and stimulates the proliferation of both types of cells. The results evidence that the Cornus mas L. fruit extract significantly reduces the level of reactive oxygen species in the cells tested and can modulate the expression of genes closely related to oxidative stress. Moreover, it suppresses the production of IL-6, IL-8, and TNF-α, and the effect was related to loganic acid and cornuside. The present research indicates that the analyzed dogwood extract can be an effective means of prevention of cell damage caused by free radicals and have a positive effect on the condition of skin cells.     

Pentathiepins: A Novel Class of Glutathione Peroxidase 1 Inhibitors that Induce Oxidative Stress,Loss of Mitochondrial Membrane Potential and Apoptosis in Human Cancer Cells

A novel class of glutathione peroxidase 1 (GPx1) inhibitors, namely tri- and tetracyclic pentathiepins, has been identified that is approximately 15 times more potent than the most active known GPx1 inhibitor, mercaptosuccinic acid. Enzyme kinetic studies with bovine erythrocyte GPx1 indicate that pentathiepins reversibly inhibit oxidation of the substrate glutathione (GSH). Moreover, no inhibition of superoxide dismutase, catalase, thioredoxin reductase or glutathione reductase was observed at concentrations that effectively inhibit GPx1. As well as potent enzyme inhibitory activity, the pentathiepins show strong anticancer activity in various human cancer cell lines, with IC₅₀ values in a low-micromolar range. A representative tetracyclic pentathiepin causes the formation of reactive oxygen species in these cells, the fragmentation of nuclear DNA and induces apoptosis via the intrinsic pathway. Moreover, this pentathiepin leads to a rapid and strong loss of mitochondrial membrane potential in treated cancer cells. On the other hand, evidence for the induction of ferroptosis as a form of cell death was negative. These new findings show that pentathiepins possess interesting biological activities beyond those originally ascribed to these compounds.