Skin Redox Balance Maintenance: The Need for an Nrf2-Activator Delivery System

Abstract

Abstract:The skin, being the largest organ of the body, functions as a barrier between our body and the environment. It is consistently exposed to various exogenous and endogenous stressors (e.g., air pollutants, ionizing and non-ionizing irradiation, toxins, mitochondrial metabolism, enzyme activity, inflammatory process, etc.) producing reactive oxygen species (ROS) and physical damage (e.g., wounds, sunburns) also resulting in reactive oxygen species production. Although skin is equipped with an array of defense mechanisms to counteract reactive oxygen species, augmented exposure and continued reactive oxygen species might result in excessive oxidative stress leading to many skin disorders including inflammatory diseases, pigmenting disorders and some types of cutaneous malignancy. The nuclear factor erythroid 2-related factor 2 (Nrf2) is an emerging regulator of cellular resistance and of defensive enzymes such as the phase II enzymes. Induction of the Keap1-Nrf2 pathway may have a beneficial effect in the treatment of a large number of skin disorders by stimulating an endogenous defense mechanism. However, prolonged and enhanced activation of this pathway is detrimental and, thus, limits the therapeutic potential of Keap1-Nrf2 modulators. Here, we review the consequences of oxidative stress to the skin, and the defense mechanisms that skin is equipped with. We describe the challenges of maintaining skin redox balance and its impact on skin status and function. Finally, we suggest a novel strategy for maintenance of skin redox homeostasis by modulating the Keap1-Nrf2 pathway using nanotechnology-based delivery systems.

The Cutaneous Physiological Redox: Essential to Maintain but Difficult to Define

“…Our skin—an essential part of the integumentary system—is our interface with the external environment. It serves as a protective physical and biologic barrier, shielding our delicate internal surroundings from various insults such as air pollutants [ 13 ], ionizing and nonionizing radiation, toxins, wounds and microbial invasions [ 14 , 15 ]. The human skin is also a lush microbial habitat, hosting a wide variety of bacteria, fungi and viral species [ 16 ].…”

Equol’s Anti-Aging Effects Protect against Environmental Assaults by Increasing Skin Antioxidant Defense and ECM Proteins While Decreasing Oxidative Stress and Inflammation

“…Many major cosmetic companies have anti-pollution personal care products, but, in general, the products are formulated with commonly used active ingredients that have been in the marketplace for some time and have been retooled using marketing strategies to address current environmental pollution treatments to improve dermal health. Equol is a botanical compound with polyphenolic chemical characteristics found in plant and food products, and it is also classified as an isoflavonoid [12,76]. Moreover, equol appears to address the need as a new active ingredient in personal care products to protect against pollution assaults by increasing antioxidant defense, while inhibiting oxidative stress and inflammation [2,78].…”

“…In addition to dietary intake of vitamins and supplementation of antioxidant ingredients, other plant-derived compounds, such as equol, are known to stimulate Nfr2 and increase endogenous detoxifying enzymes and antioxidant production [2,73]. Finally, a recent review by Greenwald et al, in 2016, described a need for a Nfr2 activator in human skin to maintain dermal redox balance in modulating the Keap 1-Nrf2 pathway for antioxidant defense [76].…”

“…Therefore, in brief, equol itself is a very strong antioxidant, and, in turn, it can increase the levels of the master gene, Nrf2, which regulates the endogenous expression of detoxifying proteins and many other antioxidant enzymes that are involved in wound repair, protection against skin cancer, and where Nrf2 activation guards against dermal damage, from sunlight (ionizing radiation) and oxidative stress via ROS [2,[69][70][71][72][73]76,99].…”

Vichy Thermal Spring Water (VTSW), a cosmetic ingredient of potential interest in the frame of skin ageing exposome: an in vitro study

“…This thioredoxine system is one of the major antioxidant defense systems which maintains glutathione status . In this respect, GCLM encodes the catalytic subunit of glutamate‐cysteine ligase, an enzyme essential for the synthesis of glutathione , a key factor in the maintenance of cell redox potential and in a number of reactions of detoxification and elimination of reactive oxygen species. The genes encoding GSR and GPX2, 2 enzymes essential to this system are also overexpressed in the presence of VTSW.…”