Oroxylin A ameliorates ultraviolet radiation-induced premature skin aging by regulating oxidative stress via the Sirt1 pathway.

Skin is susceptible to premature aging in response to ultraviolet (UV) radiation-induced oxidative stress, which can ultimately result in aberrant aging or age-related disorders. Accordingly, strategies that can be adopted to mitigate oxidative stress may contribute to protecting skin from induced aging-related damage, thereby offering promising approaches for the treatment of skin diseases and disorders. In this regard, oroxylin A (OA), a natural flavonoid isolated from certain plants used in traditional Chinese medicine, is considered to have notable antioxidant, anti-inflammatory, and anti-apoptotic properties, and is often used to treat certain inflammatory diseases. To date, however, there has been comparatively little research on the effects of OA with respect skin aging. In this study, we utilized UV radiation-induced mouse and cellular models of aging to assess the efficacy of OA in protecting against skin aging. Subsequently, to elucidate the potential mechanisms underlying the protective effect of OA on skin aging, we performed molecular docking analysis to investigate the involvement of the anti-aging gene Sirt1, which was further confirmed on the basis of Sirt1 gene silencing. We accordingly demonstrated that by promoting an increase in the expression of Sirt1, OA can contribute to suppressing UV-induced skin photo-aging in cells/mice by reducing oxidative stress. Furthermore, we established that by activating Sirt1, OA can also promote the dissociation of Nrf2 from Keap1 and its subsequent nuclear translocation. Collectively, our findings in this study reveal OA to be an effective natural compound that can be administered to delay the aging of skin triggered by UV, both in vivo and in vitro, by binding to Sirt1 to promote the deacetylation and nuclear translocation of Nrf2, thereby contributing to a reduction in oxidative stress. These findings may this provide a therapeutic target for the prevention of skin aging or aging-induced skin diseases.

ErZhiFormula prevents UV-induced skin photoaging by Nrf2/HO-1/NQO1 signaling: An in vitro and in vivo studies.

ETHNOPHARMACOLOGICAL RELEVANCE: ErZhiFormula (EZF) is a classical traditional Chinese medicinal formulation. It can be used to treat liver and kidney yin deficiency, dizziness, lumbar debility, insomnia, nocturnal emission, lower extremity weakness, and other aging-related diseases. However, the protective effect of EZF in skin photoaging and its potential mechanism has not been clarified. AIM OF THE STUDY: This study aims to explore the role of EZF in the skin photoaging mechanism induced by UV radiation. MATERIALS AND METHODS: Ultra Performance Liquid Chromatography (UPLC) was used to identify the fingerprint of EZF. The mice were irradiated with UVA and UVB to establish the photoaging model in vivo. Human immortalized keratinocytes (HaCaT) were irradiated with UVB to establish the photoaging model in vitro. The activity of cells was detected by CCK-8 and LDH kits, the level of reactive oxygen species was detected by DCF fluorescent probe, and the apoptosis was detected by PE annexin V and 7-Amino-Actinomycin (7-AAD) staining. Comet assay was used to detect cell DNA damage. The antioxidant enzyme levels in cell and mouse serum were detected by antioxidant kit, and Western blot was used to detect protein expression. RESULTS: We found that EZF contain many active ingredients, including salidroside, specnuezhenide, isoquercitrin, etc. EZF can improve the photoaging of HaCaT cells and mouse skin caused by UV radiation. The results of animal experiments are consistent with those of cell experiments. Combined with Western blot analysis, we found that EZF finally played an anti-skin photoaging role by regulating the Nrf2/HO-1/NQO1 pathway. CONCLUSIONS: EZF can protect skin from UV-induced photoaging by regulating the Nrf2/HO-1/NQO1 signal pathway. EZF may become a traditional Chinese medicine with the potential to prevent skin photoaging.

Modified Qing'e Formula protects against UV-induced skin oxidative damage via the activation of Nrf2/ARE defensive pathway.

Exposure to ultraviolet (UV) light triggers the rapid generation and accumulation of reactive oxygen species (ROS) in skin cells, which increases oxidative stress damage and leads to photoaging. Nuclear factor E2-related factor 2 (Nrf2) modulates the antioxidant defense of skin cells against environmental factors, especially ultraviolet radiation. Natural products that target Nrf2-regulated antioxidant reactions are promising candidates for anti-photoaging. The aim of this study was to investigate the protective effect of Modified Qing'e Formula (MQEF) on UV-induced skin oxidative damage and its molecular mechanisms. In this study, the photoaging models of human keratinocytes (HaCaT) and ICR mice were established by UV irradiation. In vitro models showed that MQEF displayed potent antioxidant activity, significantly increased cell viability and reduced apoptosis and excess ROS levels. Meanwhile, the knockdown of Nrf2 reversed the antioxidant and anti-apoptotic effects of MQEF. In vivo experiments indicated that MQEF could protect the skin against UV-exposed injury which manifested by water loss, sensitivity, tanning, wrinkling, and breakage of collagen and elastic fibers. The application of MQEF effectively increased the activity of antioxidant enzymes and reduced the content of malondialdehyde (MDA) in mice. In addition, MQEF was able to activate Nrf2 nuclear translocation in mouse skin tissue. In summary, MQEF may attenuate UV-induced photoaging by upregulating Nrf2 expression and enhancing antioxidant damage capacity. MQEF may be a potential candidate to prevent UV-induced photoaging by restoring redox homeostasis.

Corylin from Psoralea fructus (Psoralea corylifolia L.) protects against UV-induced skin aging by activating Nrf2 defense mechanisms.

Oxidative stress damage can lead to premature skin aging or age-related skin disorders. Therefore, strategies to improve oxidative stress-induced aging are needed to protect the skin and to treat skin diseases. This study aimed to determine whether the flavonoid corylin derived from Psoralea corylifolia can prevent UV-induced skin aging and if so, to explore the potential molecular mechanisms. We found that corylin potently blocked UV-induced skin photoaging in mice by reducing oxidative stress and increasing the nuclear expression of nuclear factor-erythroid factor 2-related factor 2 Nrf2. We also found that corylin stimulated Nrf2 translocation into the nucleus and increased the delivery of its target antioxidant genes together with Kelch-like ECH-associated protein 1 (Keap1) to dissociate Nrf2. These findings indicate that corylin could prevent skin aging by inhibiting oxidative stress via Keap1-Nrf2 in mouse cells. Thus, Nrf2 activation might be a therapeutic target for preventing skin aging or skin diseases caused by aging. Our findings also provided evidence that warrants the further investigation of plant ingredients to facilitate the discovery of novel therapies targeting skin aging.