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Review
. 2023 Feb 13;24(4):3755.
doi: 10.3390/ijms24043755.

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

Hui-Min Liu  1   2 , Ming-Yan Cheng  1 , Meng-Han Xun  1 , Zhi-Wei Zhao  1 , Yun Zhang  1 , Wei Tang  1 , Jun Cheng  1 , Jia Ni  1 , Wei Wang  1   2
Affiliations
Review

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

Hui-Min Liu et al. Int J Mol Sci. .

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.

Keywords: ROS; cancer; inflammation; oxidative stress; plant polyphenols; signaling pathways; skin cellular senescence.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Oxidative damage of biological macromolecules.
Figure 2
Figure 2
Skin oxidative stress-related signaling pathways. Exogenous stimuli (e.g., UV, chemicals, and PM2.5) and/or endogenous factors (e.g., mitochondrial oxidase and metabolism) induce ROS overproduction. ROS activate the antioxidant defense system and promote the expression of antioxidant enzymes through Nrf2 and SIRT1/FOXO pathways, which in turn reduce ROS production. When the antioxidant defense system fails to completely scavenge ROS, oxidative stress is induced. Excessive ROS activate MAPK, JAK/STAT, PI3K/AKT/mTOR, and NF-κB signaling pathways, thereby resulting in the expression of cytokines associated with skin cellular senescence, inflammation, and cancer. The transforming growth factor-β signaling pathway, related to collagen synthesis, is inhibited by ROS and the transcription factor AP-1 to accelerate skin cellular senescence.
Figure 3
Figure 3
The regulatory mechanism of plant polyphenols.
See this image and copyright information in PMC

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Grants and funding

This research was funded by Shanghai Alliance Program, grant number LM201941.
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