NRF2 in dermo‐cosmetic: From scientific knowledge to skin care products

Abstract

The skin is the organ that is most susceptible to the impact of the exposome.Located at the interface with the external environment, it protects internal organs through the barrier function of the epidermis. It must adapt to the consequences of the harmful effects of solar radiation, the various chemical constituents of atmospheric pollution, and wounds associated with mechanical damage: oxidation, cytotoxicity, inflammation, and so forth. In this biological context, a capacity to adapt to the various stresses caused by the exposome is essential; otherwise, more or less serious conditions may develop accelerated aging, pigmentation disorders, atopy, psoriasis, and skin cancers. Nrf2-controlled pathways play a key role at this level. Nrf2 is a transcription factor that controls genes involved in oxidative stress protection and detoxification of chemicals. Its involvement in UV protection, reduction of inflammation in processes associated with healing, epidermal differentiation for barrier function, and hair regrowth, has been demonstrated. The modulation of Nrf2 in the skin may therefore constitute a skin protection or care strategy for certain dermatological stresses and disorders initiated or aggravated by the exposome. Nrf2 inducers can act through different

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“…Nrf2 is located in the cytoplasm of the cells in its inactive state bound to Kelch-like ECHassociated protein 1 (Keap1) [220]. When cells are undergoing oxidative stress, Nrf2 translocates to the nucleus and binds to the antioxidant responsive element (ARE), thus activating target genes and the process of detoxification [220][221][222]. Nrf2 is involved in removing ROS, chemical detoxification, reducing inflammation in wound healing, skin protection, photo protection and pigmentation [221].…”

“…When cells are undergoing oxidative stress, Nrf2 translocates to the nucleus and binds to the antioxidant responsive element (ARE), thus activating target genes and the process of detoxification [220][221][222]. Nrf2 is involved in removing ROS, chemical detoxification, reducing inflammation in wound healing, skin protection, photo protection and pigmentation [221]. Nrf2 increases synthesis of detoxifying enzymes, such as glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione S-transferase (GST), gluthathione (GSH), catalase (CAT), heme oxygenase 1 (HO-1), NAD(PH):quinone oxidoreductase (NQO1,), etc.…”

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“…Furthermore, natural defense mechanisms alone are not sufficient to protect the skin and its cells against such harmful effects of UV radiation. Hence, the inflammatory and oxidative effects of UV radiation on human skin will lead to an increased propensity for the development of several skin diseases, such as atopic dermatitis, psoriasis, acne, and even skin cancer, and are also the main cause of premature/accelerated aging and the development of a decreased capacity for skin regeneration ( Figure 1 ) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ].…”

Deletion of NRF2 disturbs composition, morphology, and differentiation of the murine tail epidermis in chronological aging

“…in Reference 11). The possibility to modulate NRF2 activity with drugs or through dietary interventions and natural, plant‐derived compounds created significant commercial interest also in the skin care field 15 . In the skin, however, NRF2 has additional specific functions as it regulates keratinocyte (KC) proliferation and differentiation, it modulates epidermal specific inflammatory genes, and most importantly provides specific constitutive and adaptive cascades that are essential for the challenges the epidermis and the whole skin are exposed to 11,16 .…”

“…The possibility to modulate NRF2 activity with drugs or through dietary interventions and natural, plant‐derived compounds created significant commercial interest also in the skin care field. 15 In the skin, however, NRF2 has additional specific functions as it regulates keratinocyte (KC) proliferation and differentiation, it modulates epidermal specific inflammatory genes, and most importantly provides specific constitutive and adaptive cascades that are essential for the challenges the epidermis and the whole skin are exposed to. 11 , 16 A NRF2 gradient from basal toward the outermost differentiated strata of the epidermis provides an inside out protective barrier that at the same allows for maximal antioxidant defenses at the outside while allowing the basal cells to still undergo cell death after exposure to potentially genotoxic extrinsic stressors, especially upon short wavelength UV radiation.…”