Possible Mechanisms of Oxidative Stress-Induced Skin Cellular Senescence, Inflammation, and Cancer and the Therapeutic Potential of Plant Polyphenols

Abstract

As the greatest defense organ of the body, the skin is exposed to endogenous and external stressors that produce reactive oxygen species (ROS). When the antioxidant system of the body fails to eliminate ROS, oxidative stress is initiated, which results in skin cellular senescence, inflammation, and cancer. Two main possible mechanisms underlie oxidative stress-induced skin cellular senescence, inflammation, and cancer. One mechanism is that ROS directly degrade biological macromolecules, including proteins, DNA, and lipids, that are essential for cell metabolism, survival, and genetics. Another one is that ROS mediate signaling pathways, such as MAPK, JAK/STAT, PI3K/AKT/mTOR, NF-κB, Nrf2, and SIRT1/FOXO, affecting cytokine release and enzyme expression. As natural antioxidants, plant polyphenols are safe and exhibit a therapeutic potential. We here discuss in detail the therapeutic potential of selected polyphenolic compounds and outline relevant molecular targets. Polyphenols selected here for study according to their structural classification include curcumin, catechins, resveratrol, quercetin, ellagic acid, and procyanidins. Finally, the latest delivery of plant polyphenols to the skin (taking curcumin as an example) and the current status of clinical research are summarized, providing a theoretical foundation for future clinical research and the generation of new pharmaceuticals and cosmetics.

Hidden route of protein damage through confined oxygen gas

“…The pO2 levels in the skin/eye tissues are not particularly substantial compared to other tissues, but rather in hypoxic to moderate conditions 28,64,65 . Their antioxidant defense systems [66][67][68] , which target freely-diffusing ROS, will further mitigate the oxidative stress. Remarkably, the O2-confinement oxidation described here can attack proteins by evading the antioxidant networks through the initial O2 trapping.…”

Troxerutin suppress inflammation response and oxidative stress in jellyfish dermatitis by activating Nrf2/HO-1 signaling pathway

“…In addition, the MAPK signaling pathway mediates phosphorylation events that activate several transcription factors linked to inflammation, which is related to the NF-kappaB pathway ( 36 , 37 ). ROS overproduction-induced cytotoxicity is regulated by the release of cytokines as a result of the translocation of nuclear factor NF-kappaB p65 ( 38 ). According to recent studies, TE dramatically enhances oxidative stress in mouse skin tissues by regulating the production of proteins linked to the NF-κB and MAPK pathways ( 18 ).…”

The Skin and Inflamm-Aging

“…UV irradiation of the epidermis results in the production of ROS in keratinocytes, leading to oxidative stress, which can cause mitochondrial and cell damage [55]. In an unfortunate cycle, this oxidative stress induced by UV radiation leads to heightened production of ROS, which contributes to the initiation of inflammation and the activation of pro-inflammatory cytokines such as IL-2, IL-6 and TNF-α [56]. This process involves multiple pathways, including the induction of gene expression through transcription factors such as NF-κB, hypoxia-inducible factor 1-alpha (HIF-1α), nuclear factor erythroid 2-related factor 2 (Nrf-2) and activator protein 1 (AP-1).…”