Emerging Therapeutic Strategies for Nrf2-Associated Skin Disorders: From Photoaging to Autoimmunity.

Age-related changes in oxidative damage to lipids and DNA in rat skin

Skin, our first interface to the external environment, is subjected to oxidative stress caused by a variety of factors such as solar ultraviolet, infrared and visible light, environmental pollution, including ozone and particulate matters, and psychological stress. Excessive reactive species, including reactive oxygen species and reactive nitrogen species, exacerbate skin pigmentation and aging, which further lead to skin tone unevenness, pigmentary disorder, skin roughness and wrinkles. Besides these, skin microbiota are also a very important factor ensuring the proper functions of skin. While environmental factors such as UV and pollutants impact skin microbiota compositions, skin dysbiosis results in various skin conditions. In this review, we summarize the generation of oxidative stress from exogenous and endogenous sources. We further introduce current knowledge on the possible roles of oxidative stress in skin pigmentation and aging, specifically with emphasis on oxidative stress and skin pigmentation. Meanwhile, we summarize the science and rationale of using three well-known antioxidants, namely vitamin C, resveratrol and ferulic acid, in the treatment of hyperpigmentation. Finally, we discuss the strategy for preventing oxidative stress-induced skin pigmentation and aging.

Most mobile phones emit 900 MHz of radiation that is mainly absorbed by the external organs. The effects of 900 MHz of radiation on fibrosis, lipid peroxidation, and anti-oxidant enzymes and the ameliorating effects of melatonin (Mel) were evaluated in rat skin. Thirty Wistar-Albino rats were used in the study. The experimental groups were the control group, the irradiated group (IR), and the irradiated+Mel treated group (IR+Mel). A dose of 900 MHz, 2 W radiation was applied to the IR group every day for 10 days (30 min/day). The IR+Mel group received 10 mg/kg/day melatonin in tap water for 10 days before the irradiation. At the end of the 10th day, a skin specimen was excised from the thoracoabdominal area. The levels of malondialdehyde (MDA) and hydroxypyroline and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were studied in the skin samples. MDA and hydroxyproline levels and activities of CAT and GSH-Px were increased significantly in the IR group compared to the control group (p<0.05) and decreased significantly in the IR+Mel group (p<0.05). SOD activity was decreased significantly in the IR group and this decrease was not prevented by the Mel treatment. These results suggest that rats irradiated with 900 MHz suffer from increased fibrosis and lipid peroxidation (LPO). Mel treatment can reduce the fibrosis and LPO caused by radiation.

피부는 끊임없이 외부환경에 노출되며 가장 주요한 스트레스 요인 중 하나는 자외선방사이다. 자외선 방사로 인하여 피부에 염증, 착색, 광노화 및 피부암을 포함하는 생물학적 영향을 끼치게 된다. 본 연구에서는 해양천연소재 (김, 다시마, 모려, 모자반, 미역, 석결명, 우뭇가사리, 청각, 톳, 파래)로부터 피부보호 항산화제를 조사하기 위해 자외선으로부터 기인된 세포보호 효과를 증명하였으며 세포독성, 산화에 의한 세포사멸, 항노화 효과에 대하여 평가를 실시하였다. 그 결과, 모자반, 한천, 석결명, 청각 에탄올 추출물을 처리한 군이 자외선으로 유도된 세포독성 및 세포사멸을 효과적으로 억제하는 것으로 나타났다. 또한 다른 실험에서 자외선에서 인한 세포사멸은 세포내 축적이나 ROS로부터 매개되지만 해양추출물을 처리함으로써 현저하게 감소되었다. 이러한 해양추출물의 보호효과 증가는 Type I collagen과 Type I procollagen에 의해 매개하는 것과 연관되는 것으로 사료된다. 이들의 결과는 해양추출물이 노화예방 및 항산화제로서의 우수한 특성으로 피부손상에 의한 산화적 스트레스에 대응하는 새로운 기능성 소재로서의 가능성을 가지는 것으로 평가된다. The skin is continuously exposed to environmental stresses. One of the most important stress factor is UV radiation. UV radiation causes a variety of biological effects on the skin, including inflammation, pigmentation, photoaging and cancer. Therefore in this study, we tried to search for skin-protective antioxidant materials from marine natural products (Porphyra Thalli, Laminariae japonicae thallus, Ostreae Concha, Sargassum Thallus, Undaria thallus, Haliotidis Concha, Agar, Codium thalli, Hizikia fusiforme thalli; HFE, Thalli) which exhibit protective activities against UVB-induced cytotoxicity and oxidative cell death and antiaging effects. As a results, UVB-induced cytotoxicity and cell death were effectively suppressed by treatment of Sargassum Thallus, Agar, Haliotidis Concha, Codium thalli, Thalli ethanol extracts. UVB-induced cell death was mediated by intracellular accumulation or ROS, which was significantly inhibited by treatment with marine natural products extracts. Also, The protective effect of these marine natural products seemed to be mediated by increased expression of type I collagen and Type I procollagen. These results suggest that marine natural products may have anti-aging effects new functional materials against oxidative stress-mediated skin damages.

Fe overload is a common consequence of the anaemia treatment, increasing the oxidative stress and promoting the accumulation of damaged biomolecules, with the subsequently impairment of cell functions. Oxidative stress and the role of folic acid preventing free radical damage have been extensively studied; nevertheless, no studies are available about the influence of folic acid-supplemented goat milk consumption on the oxidative stress-mediated damage. The objective of the present study was to assess the influence of folic acid supplementation of goat milk- or cow milk-based diets, after Fe-overload treatment to palliate anaemia, on oxidative stress-mediated biomolecular damage in the liver, brain, erythrocytes, duodenal mucosa and plasma. Control and anaemic rats were fed goat milk- or cow milk-based diets, either with normal Fe or Fe overload (450 mg/kg), and normal folic acid (2 mg/kg) or folic acid supplemented (40 mg/kg) for 30 days. During chronic Fe repletion, background DNA damage was significantly lower in anaemic rats fed folic acid-supplemented goat milk-based diet, as revealed by tail DNA (%), and folic acid-supplemented goat milk also had a beneficial effect, reducing the extent of lipid peroxidation in liver, plasma, erythrocytes and especially in brain and duodenal mucosa. Furthermore, protein oxidative damage was lower in anaemic rat duodenal mucosa for all goat milk-based diets. Folic acid supplement in goat milk avoids the undesirable effects of Fe overload during anaemia recovery in all the tissues studied, especially in the liver and duodenal mucosa, which are the tissues with higher exposition to dietary Fe.

Skin photoaging, primarily caused by ultraviolet (UV) radiation, leads to skin metabolic disorders, which have adverse psychological and physiological effects on individuals. However, traditional medications for repairing skin photoaging cause side effects. Natural bioactive compounds have been shown to prevent and treat skin photoaging with fewer side effects. Epigallocatechin gallate (EGCG), the main substance in tea polyphenols, is a natural bioactive compound with a range of properties. This review summarizes the beneficial effects and mechanisms of EGCG, as well as the application forms of EGCG in repairing photoaged skin. Results indicated that EGCG has repair effects, including improving elasticity, enhancing moisturization, inhibiting damage, and reducing pigmentation of photoaged skin. It has also been demonstrated that EGCG delivery systems, modified EGCG, and combinations with other bioactive substances could be used for repairing photoaged skin due to its poor stability and low bioavailability. EGCG effectively repairs various types of skin damage caused by UV radiation while maintaining normal skin structure and function. It is, therefore, an effective candidate for repairing photoaged skin. These results could provide references for the development and application of EGCG products for the treatment of photoaged skin.

ABSTRACTObjectives: We investigated the mutual effects of overt hypothyroidism and prolonged sunlight exposure on free radical accumulation and oxidative skin damage.Methods: Free radical accumulation was evaluated by monitoring the transformation of 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) into MTT-formazan. The pro-oxidant enzymes xanthine oxidase (XO) and NADPH-diaphorase were measured in the skin. XO activity was estimated based on the yield of uric acid, while NADPH-diaphorase reactivity was monitored histochemically as an indirect marker of nitric oxide synthase and nitric oxide activity. Cellular damage was determined by malondialdehyde formation, a marker for lipid peroxidation.Results: In the skin of both euthyroid and hypothyroid animals, solar simulated ultraviolet irradiance increased the activity of XO and the NADPHdiaphorase reactivity as a protective response to formation of free radicals, such as reactive oxygen or nitrogen species. These pro-oxidant enzymes diminished in hypothyroid rats. Accumulation of the same amount of free radicals led to similar peroxidation in both hypothyroid and irradiated euthyroid rats. Hypothyroid skin after UV-exposure showed even greater lipid peroxidation.Discussion: The hypothyroid state could be a risk factor for enhanced oxidative skin damage in chronic photo-exposed skin due to oxidative stress. The lipid peroxidation is one of the major pathways by which photo-oxidative stress promotes photocarcinogenesis and photo-aging.

Cross-generational trans fat intake exacerbates UV radiation-induced damage in rat skin

Oxidative stress, caused by an imbalance between reactive oxygen species (ROS) production and antioxidant defense mechanisms, has a profound effect on skin health. This imbalance contributes to skin damage, premature aging, and the development of various dermatological conditions by modulating key signaling pathways with pro-inflammatory or antioxidant effects, such as NF-κB, JAK/STAT, Nrf2, MAPK/AP1, and SIRT1/FOXO. So, the application of antioxidant compounds, particularly those derived from natural sources, is essential for protecting the skin against ROS-induced damage. Sea cucumber, a marine invertebrate known for its remarkable regenerative capacity, contains bioactive compounds, including phenolics, proteins, and polysaccharides, which exhibit antioxidative and anti-inflammatory properties. These bioactive components may offer protective effects against oxidative stress within the skin. Therefore, this study will first evaluate the potential of sea cucumber-derived bioactive compounds in mitigating oxidative stress by examining their ability to counteract ROS-induced cellular damage caused by ROS and their potential role in promoting skin repair and regeneration. The review will also discuss the underlying mechanisms, including key signaling pathways, and explore the therapeutic potential of sea cucumber-derived exosomes as a novel strategy to treating oxidative stress-related skin disorders. Finally, a comparison is made between the efficacy of the sea cucumber crud extract with its derived exosome in treating oxidative stress-induced skin damage.

Chapter 25 - Protective role of natural products and bioactive compounds in multiple sclerosis

Acute exposure of eukaryotic cells to ultraviolet-B (UVB) radiation leads to a number of detrimental effects, one such prominent effect of UVB exposure is increased production of free radicals which can lead to oxidative damage. Although, the human skin is well equipped with endogenous antioxidant defence system, often increased levels of free radicals lead to oxidative damage in skin. Skin inflammation, accelerated skin aging, and formation of wrinkles are all consequences of UVB induced photodamage. Hence, it is posited that supplementation of an exogenous antioxidant derived from natural products could prevent and reduce oxidative damage in skin cells. This study set forth to investigate the antioxidative role of terpenoid rich Canarium odontophyllum Miq. (Dabai) extract on acute UVB-induced photodamage human keratinocyte cells (HaCaT). We first evaluated the antioxidative capacity of increasing concentrations of crude extracts of TRCO Dabai extracts (62.50 µg/mL, 125 µg/mL, 250 µg/mL, and 500 µg/mL) through FRAP assay. We found all the tested TRCO extract exhibited antioxidative capacity in dosage dependent manner. We further investigated the effects of pre-treatment 250 µg/mL and 500 µg/mL TRCO on UVB-induced photodamaged HaCaT cell by measuring oxidative stress markers of lipid peroxide (LPO content), protein carbonyl (PC) content, glutathione peroxidase (GSH-Px) and glutathione-S-transferase (GST) activities. Both 250 µg/mL and 500 µg/mL TRCO extract pre-treated UVB-induced HaCaT cell group exhibited significantly reduced lipid peroxides content and GST activity compared to the positive control (p&lt;0.05). Pre-treatment of 250 µg/mL TRCO extract significant enhanced GSH-Px activity (p&lt;0.05). However, no significant difference in protein carbonyl content could be established across all tested groups. Therefore, our results suggest that TRCO extract can offer protection against oxidative damages caused by UVB exposure, and said protective effects can be attributed by its antioxidant properties.

UVA radiation induces oxidative stress, mitochondrial dysfunction, and cell death in human dermal fibroblasts, contributing to skin aging and damage. In this study, we investigated the protective effects of polydatin, a natural polyphenol, against UVA-induced cell damage. Our results show that polydatin preserves cell viability and reduces intracellular reactive oxygen species (ROS) levels after UVA exposure. In addition, polydatin maintains mitochondrial integrity by preserving mitochondrial membrane potential and improving mitochondrial respiration. From a molecular perspective, polydatin regulates the expression of Nrf2, a key regulator of the cellular antioxidant response, thereby promoting cellular defense mechanisms. Additionally, polydatin attenuates UVA-induced mitochondrial fission, supporting a balanced mitochondrial dynamic profile. These results suggest that polydatin exerts a protective effect on UVA-irradiated fibroblasts, highlighting its potential for cosmetic and dermatological applications aimed at preventing photoaging and oxidative skin damage.

Ferroptosis and Nrf-2 signaling: a redox tug of war in leishmaniasis pathogenesis and host directed therapy.

Influence of UV exposure on DNA damage in Chinese skin

The skin, being the largest organ of the human body, serves as the primary barrier against external insults, including UV radiation, pollutants, and microbial pathogens. However, prolonged exposure to these environmental stressors can lead to the generation of reactive oxygen species (ROS), causing oxidative stress, inflammation, and ultimately, skin aging and diseases. Antioxidants play a crucial role in neutralizing ROS and preserving skin health by preventing oxidative damage. In recent years, nanotechnology has emerged as a powerful tool for enhancing the delivery of antioxidants onto the skin. In particular, liposomal formulations have offered unique advantages such as improved stability, controlled release, and enhanced penetration through the skin barrier. This has led to a surge in research focused on developing liposomal-based antioxidant delivery systems tailored for skin health applications. Through a comprehensive analysis of the literature from the 2019-2024 period, this review provides an overview of emerging trends in the use of liposomal delivery systems developed for antioxidants aimed at improving skin health. It explores the latest advancements in liposomal formulation strategies, vesicle characterization, and their applications in delivering antioxidants to combat oxidative stress-induced skin damage and other associated skin pathologies. A comparison of various delivery systems is conducted for the most common antioxidants. Finally, a brief analysis of lipid nanovesicles used in the cosmeceutical industry is provided.