Redox Biology of Skin Aging and Carcinogenesis: the Role of Natural Antioxidants as Potential Protective Agents

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Background

Promoting healthy human ageing is one of the most important challenges and opportunities of the 21st century worldwide. Photodamage of the skin caused by acute or chronic sun exposure leading to premature skin aging and cancers has become important dermatological problems associated with high cost of treatment and skin care. Oxidative stress induced by ultraviolet radiation (UVR) can compromise skin function and its structural support responsible for premature aging characterized by thinning of dermis, loss of elasticity and irregular pigmentation. Responses of skin cells to oxidative stress include stimulation of tyrosinase-mediated melanogenesis in melanocytes leading to hyperpigmentation. Additionally, UVR-mediated oxidative stress results in upregulation of certain members of the matrix metalloproteinase (MMP) family responsible for collagen destruction, a hallmark of skin aging. Due to the harm of UV light, it is recommended to use photoprotective agents, in particular sunscreen, although their photoprotective effects could be insufficient when there is an excessive oxidative stress. Thus, there is a rising demand for photoprotective agents and several natural and synthetic compounds are under intensive development. However, they remain challenging because there is no entirely satisfactory outcome and many agents cause adverse effects. UVR, in particular UVA, can stimulate production of reactive oxygen species (ROS) and/or deteriorate the endogenous antioxidant defense network, eventually leading to photo-oxidative stress of the skin in association with upregulation of tyrosinase and interstitial collagenase (MMP-1), which initiates cleavage of fibrillar collagen in skin. Improvement of antioxidant defense system to cope with the overwhelmed oxidative stress could thus be one of effective and safe approaches to delay the aging process and prevent photocarcinogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important transcription factor controlling the antioxidant response in various tissues including the skin, plays a crucial role in cellular function and integrity by protecting skin cells against oxidative insults. Thus, attempts have been made to investigate the role of compounds targeting Nrf2-regulated antioxidant defense in protection against UVR-mediated photoaging and photocarcinogenesis.

Natural products including diet- and plant-derived phytochemicals have gained remarkable attention as promising candidates for effective photoprotective agents due to their antioxidant properties. Antioxidant phytochemicals are abundantly present in plant-based diets and are active ingredients in several medicinal herbs. Several studies have revealed that some herbal extracts and phytochemicals have abilities to inhibit UVR-mediated upregulation of MMPs including MMP-1 through an antioxidant mechanism involving Nrf2 signaling. Thus, we would like to bring together experts from related disciplines to discuss the role of natural antioxidants in photoaging and photocarcinogenesis through regulation of antioxidant defense system that would provide insight into development of effective pharmacological approaches to photoprotection against UVR-induced skin damage.

Important Notes

General:
- Positive and negative controls - Lack of positive and negative controls are not acceptable.
-Irrelevant or implausible models - The relevance and plausibility of a model system from which results of a study are being derived must be carefully considered. This includes consideration of the value and ethical implications of further in vivo studies which replicate previously published results in well studied species.

Chemical:
- Composition of the study material - Manuscripts relating to crude plant extracts, where an individual active agent or a detailed phytochemical characterization of all extracts is not clearly identified and quantified are not acceptable. The composition of the study material must be described adequately.
- Composition of the study material - Where ‘pure’ compounds are used the level of purity must be reported.
- Irrelevant dose ranges - Testing extracts at implausibly high doses is not acceptable.
- Antioxidant activity - Simple in silico and pharmacologically irrelevant assays for antioxidant activity (e.g. the DPPH assay, FRAP (Ferric Reducing Ability of Plasma), ABTS (2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) are not acceptable as a main tool for assessing an extract or a compound for activity.

Botanical:
- The identification of the study material needs to be defined well. All species should be fully validated using www.theplantlist.org orhttp://mpns.kew.org/mpns-portal/.
- Full botanical documentation is essential (i.e. a voucher specimen deposited in a recognized herbarium).

Keywords: antioxidant, oxidative stress, photoaging, photocarcinogenesis, ultraviolet

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