Linoleic Acid Induces Metabolic Reprogramming and Inhibits Oxidative and Inflammatory Effects in Keratinocytes Exposed to UVB Radiation.

Linoleic acid (LA), the primary ω-6 polyunsaturated fatty acid (PUFA) found in the epidermis, plays a crucial role in preserving the integrity of the skin's water permeability barrier. Additionally, vegetable oils rich in LA have been shown to notably mitigate ultraviolet (UV) radiation-induced effects, including the production of reactive oxygen species (ROS), cellular damage, and skin photoaging. These beneficial effects are primarily ascribed to the LA in these oils. Nonetheless, the precise mechanisms through which LA confers protection against damage induced by exposure to UVB radiation remain unclear. This study aimed to examine whether LA can restore redox and metabolic equilibria and to assess its influence on the inflammatory response triggered by UVB radiation in keratinocytes. Flow cytometry analysis unveiled the capacity of LA to diminish UVB-induced ROS levels in HaCaT cells. GC/MS-based metabolomics highlighted significant metabolic changes, especially in carbohydrate, amino acid, and glutathione (GSH) metabolism, with LA restoring depleted GSH levels post-UVB exposure. LA also upregulated PI3K/Akt-dependent GCLC and GSS expression while downregulating COX-2 expression. These results suggest that LA induces metabolic reprogramming, protecting against UVB-induced oxidative damage by enhancing GSH biosynthesis via PI3K/Akt signaling. Moreover, it suppresses UVB-induced COX-2 expression in HaCaT cells, making LA treatment a promising strategy against UVB-induced oxidative and inflammatory damage.

Butin Protects Keratinocytes From Particulate Matter 2.5 and Ultraviolet B-Mediated Damages.

BACKGROUND: Butin is a naturally occurring compound with a wide range of medicinal properties, including anti-inflammatory, anti-arthritic, and antioxidant properties. Particulate matter 2.5 (PM2.5) and ultraviolet B (UVB) radiation contribute to skin cell damage via the induction of oxidative stress. METHODS: This study sought to assess the protective effects of butin against damage triggered by PM2.5 and UVB in human HaCaT keratinocytes. Assessments were performed to evaluate cell viability, apoptosis, and cellular component damage. RESULTS: Butin exhibited its protective ability via the inhibition of PM2.5-induced reactive oxygen species generation, lipid peroxidation, DNA damage, protein carbonylation, and mitochondrial damage. Butin reduced the PM2.5-induced c-Fos and phospho-c-Jun protein levels as well as mitogen-activated protein kinase. Furthermore, butin mitigated PM2.5- and UVB-induced apoptosis. CONCLUSION: Butin had the potential as a pharmaceutical candidate for treating skin damage caused by PM2.5 and UVB exposure.

Keratinocyte derived extracellular vesicles mediated crosstalk between epidermis and dermis in UVB-induced skin inflammation.

BACKGROUND AND RATIONALE: Ultraviolet-B (UVB) light induces dermal inflammation, although it is mostly absorbed in the epidermis. Recent reports suggest extracellular vesicles (EVs) act as a mediator of photodamage signaling. Melatonin is reported to be a protective factor against UV-induced damage. We hypothesized that EVs derived from UVB-irradiated keratinocytes might trigger proinflammatory responses in dermal cells and tested whether melatonin can ameliorate UVB-induced inflammation. METHODS: We used UVB-irradiated HaCaT cells, primary keratinocytes and STING knock-out mice to model production of EVs under photodamaging conditions and performed immunoblotting and ELISA to measure their effect on dermal macrophages. RESULTS: UVB-irradiated keratinocytes produce an increased number of EVs that contain higher concentrations of DNA and protein compared with controls. KC-derived EVs (KEVs) induced a STING- and inflammasome-mediated proinflammatory response in macrophages in vitro, and a pronounced inflammatory infiltrate in mouse dermis in vivo. Melatonin ameliorated KEVs inflammatory effect both in vitro and in vivo. CONCLUSIONS: This data suggests EVs are mediators in a crosstalk that takes place between keratinocytes and their neighboring cells as a result of photodamage. Further studies exploring EVs induced by damaging doses of UVB, and their impact on other cells will provide insight into photodamage and may help develop targeted therapeutic approaches.

Visible light accelerates skin wound healing and alleviates scar formation in mice by adjusting STAT3 signaling.

During the wound healing process, the activation of signal transducer and activator of transcription 3 (STAT3) is considered crucial for the migration and proliferation of epithelial cells, as well as for establishing the inflammatory environment. However, an excessive STAT3 activation aggravates scar formation. Here we show that 450 nm blue light and 630 nm red light can differentially regulate the phosphorylation of STAT3 (p-STAT3) and its downstream cytokines in keratinocytes. Further mechanistic studies reveal that red light promotes wound healing by activating the PI3 kinase p110 beta (PI3Kß)/STAT3 signaling axis, while blue light inhibits p-STAT3 at the wound site by modulating cytochrome c-P450 (CYT-P450) activity and reactive oxygen species (ROS) generation. In a mouse scar model, skin wound healing can be significantly accelerated with red light followed by blue light to reduce scar formation. In summary, our study presents a potential strategy for regulating epithelial cell p-STAT3 through visible light to address skin scarring issues and elucidates the underlying mechanisms.

Protective Effects of Keratinocyte-Derived GCSF and CCL20 on UVB-Induced Melanocyte Damage.

The skin microenvironment created by keratinocytes (KC) influences the stress responses of melanocytes (MC) to UVB insults. This study employed RNA sequencing analysis as well as in vitro and in vivo models to elucidate the underlying mechanisms. Our RNA-Seq analysis revealed a statistically significant upregulation of GCSF and CCL20 genes in UVB-irradiated KC, correlating with the protective effects of KC on MC responses to UVB exposure. Recombinant GCSF and CCL20 exhibited the most pronounced modulation of UVB-induced MC responses. These effects included the attenuation of apoptosis and reduction of ROS formation, along with the upregulation of tyrosinase and tyrosinase-related protein-1, which are involved in the melanogenic pathway. ELISA was also used to confirm that UVB could induce the secretion of GCSF and CCL20 from KC. A similar correlation between GCSF and CCL20 expression in KC and tyrosinase levels in MC was observed in UVB-irradiated mouse skin. Our study provides novel insights into the protective role of GCSF and CCL20 in the paracrine effects of KC on UVB-induced MC damage through the modulation of stress response pathways, the MITF-tyrosinase axis, and the regulation of p53. These findings have implications for the development of pharmacological strategies targeting KC-derived paracrine factors for the prevention of skin photodamage.

Photoprotective Effects of Yeast Pulcherrimin.

Sunscreen products can protect the skin against the harmful effects of UV radiation, including reddening, aging, and cancer. The aim of this research was to evaluate the photoprotective effects of yeast pulcherrimin, an iron-chelating dipeptide. We first investigated the cytotoxicity of pulcherrimin produced by Metschnikowia pulcherrima yeast on the human keratinocyte HaCaT cell line, using the PrestoBlue assay. We assessed the ability of pulcherrimin to induce DNA repair after the exposure of HaCaT cells to oxidative stress. We also evaluated its protective activity against UVC radiation. The sun protective factor (SPF) was calculated using the Mansur equation. The UVA/UVB ratio values for pure pulcherrimin were evaluated using the Boots Star Rating system. The critical wavelength was determined by calculating the integrated optical density curve area. Based on the results, pulcherrimin shows strong cytoprotective effects through antioxidant and photoprotective activities on the HaCaT cell line. The calculated SPFs were 20 and 15 at pH = 7 and pH = 10, respectively. The critical wavelength above 370 nm and the UVA/UVB ratio R > 1 suggest that yeast pulcherrimin-a cyclic dipeptide containing iron-may be considered a promising photoprotective agent.

Anti-Photoaging Effects of Antioxidant Peptide from Seahorse (Hippocampus abdominalis) in In Vivo and In Vitro Models.

Overexposure to ultraviolet (UV) radiation can lead to photoaging, which contributes to skin damage. The objective of this study was to evaluate the effects of an antioxidant peptide (SHP2) purified from seahorse (Hippocampus abdominalis) alcalase hydrolysate on UVB-irradiated skin damage in human keratinocyte (HaCaT) and human dermal fibroblast (HDF) cells and a zebrafish model. The data revealed that SHP2 significantly enhanced cell viability by attenuating apoptosis through the reduction of intracellular reactive oxygen species (ROS) levels in UVB-stimulated HaCaT cells. Moreover, SHP2 effectively inhibited ROS, improved collagen synthesis, and suppressed the secretion of matrix metalloproteinases (MMPs) in UVB-irradiated HDF cells. SHP2 restored the protein levels of HO-1, Nrf2, and SOD, while decreasing Keap1 expression in UVB-treated HDF, indicating stimulation of the Keap1/Nrf2/HO-1 signaling pathway. Furthermore, an in vivo study conducted in zebrafish confirmed that SHP2 inhibited photoaging by reducing cell death through the suppression of ROS generation and lipid peroxidation. Particularly, 200 µg/mL of SHP2 exerted a remarkable anti-photoaging effect on both in vitro and in vivo models. These results demonstrate that SHP2 possesses antioxidant properties and regulates skin photoaging activities, suggesting that SHP2 may have the potential for use in the development of cosmetic products.

High-glucose impact on UVB responses in human epidermal keratinocytes: Insights on diabetic skin's resistance to photocarcinogenesis.

Ultraviolet (UV) B-induced damage in human epidermal keratinocytes (HEKs) initiates photocarcinogenesis. However, how diabetes influences photocarcinogenesis is not well understood. To investigate the impact of high-glucose environments on responses to UVB, we cultured HEKs in normal-glucose (NG) or high-glucose (HG) conditions (G6 and G26), followed by UVB irradiation at 25 mJ/cm2 (G6UVB and G26UVB). We performed next-generation sequencing and analyzed HEKs' expression profiles bioinformatically to identify candidate genes and cellular responses involved. We found UVB induced consistent responses in both NG- and HG-cultivated HEKs, but it also triggered certain distinct processes and pathways specifically in the HG groups. The 459 differentially expressed (DE) genes in the HG groups revealed their roles in chromatin remodeling, nucleosome assembly, and interferon signaling activation. Moreover, the 29 DE genes identified in G26UVB/G6UVB comparison, including the potent tumor suppressor gene TFPI2, were considered key genes contributing to HEKs' altered response to UVB in HG environments. UVB irradiation induced significantly higher TFPI2 expression in HG-cultivated HEKs than their NG-cultivated counterpart. Finally, HG-cultivation significantly increased oxidative stress, cyclobutane pyrimidine dimer formation, and apoptosis, while reducing HEKs' viability after UVB irradiation. These changes under HG conditions probably mediate cell fate toward death and tumor regression. Overall, our findings provide evidence and associated molecular basis on how HG conditions reduce keratinocytes' photocarcinogenic potential following UVB exposure.

Panax ginseng extract prevents UVB-induced skin photodamage by modulating VMP1-mediated ER stress.

BACKGROUND: The endoplasmic reticulum (ER) stress is a crucial toxic signaling event triggered by chronic exposure to Ultraviolet B radiation (UVB), which significantly exacerbate photodamage responses in the irradiated skin. Therefore, the identification of agents capable of inhibiting ER stress could serve as a promising therapeutic strategy for addressing the unmet clinical needs in the treatment of UVB-induced photodamage. METHODS: A UVB-irradiated mouse model was used and topical administration of Panax ginseng extract was carried out for a duration of 9 weeks. Vitamin E was used as a positive control. After 9 weeks of administration, the skin appearance, epidermal hyperplasia, infiltration of inflammatory cells, apoptosis, and collagen content were measured. The keratinocytes were irradiated with 6 mJ/cm2 UVB to establish an in vitro model. The levels of ER stress and apoptosis were investigated both in vivo and in vitro using qRT-PCR, immunoblotting, and immunofluorescence. RESULTS: Among the 14 extracts derived from 13 distinct plant species that were screened, Panax ginseng, Prunus mume, and Camellia japonica showed inhibitory effect on UVB-induced ER stress. Notably, Panax ginseng effectively inhibits collagen degradation and apoptosis in both irradiated keratinocytes and Balb/C mice skin. Furthermore, the silencing of VMP1 significantly impeded the cellular protective effect of Panax ginseng extract on UVB-irradiated keratinocytes, indicating that Panax ginseng exerts its protective effects through targeted promotion of VMP1. CONCLUSION: Our data suggest that Panax ginseng extract possess a therapeutical effect on UVB radiation-induced photodamage by promoting VMP1-mediated inhibition of ER stress.

Light-emitting diode irradiation at 590 nm combined with active substances modulates ultraviolet B radiation-induced keratinocyte inflammation.

To evaluate the efficacy of yellow light-emitting diode (LED) irradiation at 590 nm, alone or in combination with anti-inflammatory active substances against ultraviolet (UV)-induced inflammation in keratinocytes. HaCaT keratinocytes were pretreated with LED yellow light (590 nm) alone or in combination with an antiinflammatory active substance such as glycerophosphoinositol choline (GC), extract of grains of paradise (Aframomum melegueta Schum, AM), or a bisabolol and ginger root extract mixture (Bb-GE) before UVB irradiation. Following each treatment, we measured the levels of inflammatory mediators secreted by keratinocytes. HaCaT keratinocytes treated with UVB (300 mJ cm-²) and then cultured for 24 h exhibited significantly upregulated expression of proinflammatory factors, including interleukin (IL)-1α, prostaglandin E2 (PGE2), and IL-8. After pretreatment with 590 nm LED, UVB-induced inflammatory responses were significantly inhibited. Co-pretreatment with 590 nm LED irradiation and GC further inhibited the expression of IL-1α and IL-8. IL-8 expression was inhibited by co-pretreatment with 590 nm LED irradiation and AM, whereas PGE2 expression was inhibited by co-pretreatment with 590 nm LED irradiation and Bb-GE. Co-treatment with 590 nm LED irradiation and various active substances modulated UVB-induced inflammation in keratinocytes, suggesting the potential application of this approach to prevent damage caused by voluntary sun exposure in daily life.

Fermented Fish Collagen Attenuates Melanogenesis via Decreasing UV-Induced Oxidative Stress.

Excessive melanogenesis leads to hyperpigmentation-related cosmetic problems. UV exposure increases oxidative stress, which promotes melanogenesis-related signal pathways such as the PKA, microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2) pathways. Glycine is a source of endogenous antioxidants, including glutathione. Fermented fish collagen (FC) contains glycine; thus, we evaluated the effect of FC on decreasing melanogenesis via decreasing oxidative stress. The glycine receptor (GlyR) and glycine transporter-1 (GlyT1) levels were decreased in UV-irradiated keratinocytes; however, the expression levels of these proteins increased upon treatment with FC. The FC decreased oxidative stress, as indicated by the decreasing expression of NOX1/2/4, increased expression of GSH/GSSG, increased SOD activity, and decreased 8-OHdG expression in UV-irradiated keratinocytes. Administration of conditioned media from FC-treated keratinocytes to melanocytes led to decreased p38, PKC, MITF, TRP1, and TRP2 expression. These changes induced by the FC were also observed in UV-irradiated animal skin. FC treatment increased the expression of GlyR and GlyT, which was accompanied by decreased oxidative stress in the UV-irradiated skin. Moreover, the FC negatively regulated the melanogenesis signaling pathways, leading to decreased melanin content in the UV-irradiated skin. In conclusion, FC decreased UV-induced oxidative stress and melanogenesis in melanocytes and animal skin. FC could be used in the treatment of UV-induced hyperpigmentation problems.

Modulation of Photosensitizing Responses in Cell Culture Environments by Different Medium Components.

Many cell culture experiments are performed under light to evaluate the photodynamic or photosensitizing efficacy of various agents. In this study, the modulation of photosensitizing responses and phototoxicity under cell culture conditions by different medium components was investigated. The significant levels of reactive oxygen species (ROS) generated from DMEM, RPMI 1640, and MEM were observed under the irradiation of fluorescent light (FL) and white and blue LEDs, indicating that these media have their own photosensitizing properties; DMEM showed the most potent property. Phenol red-free DMEM (Pf-D) exhibited a stronger photosensitizing property than normal DMEM by 1.31 and 1.25 times under FL and blue LEDs, respectively; phenol red and riboflavin-free DMEM (PRbf-D) did not show any photosensitizing properties. The inhibitory effect on light transmission was more pronounced in DMEM than in RPMI, and the interference effect on green LED light was greatest at 57.8 and 27.4%, respectively; the effect disappeared in Pf-D. The media containing riboflavin induced strong phototoxicity in HaCaT keratinocytes by generating H2O2 under light irradiation, which was quenched by sodium pyruvate in the media. The presence of serum in the media was also reduced the phototoxicity; H2O2 levels in the media decreased serum content dependently. The phototoxicity of erythrosine B and protoporphyrin IX under FL was more sensitively pronounced in PRbf-D than in DMEM. The present results indicate that several medium components, including riboflavin, phenol red, sodium pyruvate, and serum, could modulate photosensitizing responses in a cell culture system by inducing photosensitizing activation and by interfering with irradiation efficacy and ROS generation.

Single-cell RNA-Seq analysis of molecular changes during radiation-induced skin injury: the involvement of Nur77.

Introduction: Ionizing radiation has been widely used in industry, medicine, military and agriculture. Radiation-induced skin injury is a significant concern in the context of radiotherapy and accidental exposure to radiation. The molecular changes at the single-cell level and intercellular communications during radiation-induced skin injury are not well understood. Methods: This study aims to illustrate this information in a murine model and human skin samples from a radiation accident using single-cell RNA sequencing (scRNA-Seq). We further characterize the functional significance of key molecule, which may provide a potential therapeutic target. ScRNA-Seq was performed on skin samples from a nuclear accident patient and rats exposed to ionizing radiation. Bioinformatic tools were used to analyze the cellular heterogeneity and preferential mRNAs. Comparative analysis was performed to identify dysregulated pathways, regulators, and ligand-receptor interactions in fibroblasts. The function of key molecule was validated in skin cells and in three mouse models of radiation-induced skin injury. Results: 11 clusters in human skin and 13 clusters of cells in rat skin were depicted respectively. Exposure to ionizing radiation caused changes in the cellular population (upregulation of fibroblasts and endothelial cells, downregulation of keratinocytes). Fibroblasts and keratinocytes possessed the most interaction pairs with other cell lineages. Among the five DEGs common to human and rat skins, Nur77 was highly expressed in fibroblasts, which mediated radiosensitivity by cell apoptosis and modulated crosstalk between macrophages, keratinocytes and endothelial cells in radiation-induced skin injury. In animal models, Nur77 knock-out mice (Nur77 -/-) showed more severe injury after radiation exposure than wild-type counterparts in three models of radiation-induced skin injury with complex mechanisms. Conclusion: The study reveals a single-cell transcriptional framework during radiation-induced skin injury, which provides a useful resource to uncover key events in its progression. Nur77 is a novel target in radiation-induced skin injury, which provides a potential therapeutic strategy against this disease.

Human Serum Albumin/Selenium Complex Nanoparticles Protect the Skin from Photoaging Injury.

Introduction: Photoaging-induced skin damage leads to appearance issues and dermatoma. Selenium nanoparticles (SeNPs) possess high antioxidant properties but are prone to inactivation. In this study, human serum albumin/SeNPs (HSA-SeNPs) were synthesized for enhanced stability. Methods: HSA-SeNPs were prepared by self-assembling denatured human serum albumin and inorganic selenite. The cytotoxicity of HSA-SeNPs was assessed using the MTT method. Cell survival and proliferation rates were tested to observe the protective effect of HSA-SeNPs on human skin keratinocytes against photoaging. Simultaneously, ICR mice were used for animal experiments. H&E and Masson trichromatic staining were employed to observe morphological changes in skin structure and collagen fiber disorders after UVB irradiation. Quantitative RT-PCR was utilized to measure changes in mRNA expression levels of factors related to collagen metabolism, inflammation, oxidative stress regulation, and senescence markers. Results: The HSA-SeNPs group exhibited significantly higher survival and proliferation rates of UVB-irradiated keratinocytes than the control group. Following UVB irradiation, the back skin of ICR mice displayed severe sunburn with disrupted collagen fibers. However, HSA-SeNPs demonstrated superior efficacy in alleviating these symptoms compared to SeNPs alone. In a UVB-irradiated mice model, mRNA expression of collagen type I and III was dysregulated while MMP1, inflammatory factors, and p21 mRNA expression were upregulated; concurrently Nrf2 and Gpx1 mRNA expression were downregulated. In contrast, HSA-SeNPs maintained the mRNA expression of those factors to be stable In addition, the level of SOD decreased, and MDA elevated significantly in the skin after UVB irradiation, but no significant differences in SOD and MDA levels between the HSA-SeNPs group with UVB irradiation and the UVB-free untreated group. Discussion: HSA-SeNPs have more anti-photoaging effects on the skin than SeNPs, including the protective effects on skin cell proliferation, cell survival, and structure under photoaging conditions. HSA-SeNPs can be used to protect skin from photoaging and repair skin injury caused by UVB exposure.

Tapinarof and its structure-activity relationship for redox chemistry and phototoxicity on human skin keratinocytes.

Tapinarof (3,5-dihydroxy-4-isopropylstilbene) is a therapeutic agent used in the treatment of psoriasis (VTAMA®). In this study, we examined the redox behaviour, (photo)stability, (photo)toxicity and (bio)transformation of tapinarof in the context of a structure-activity relationship study. Selected derivatives of the structurally related tapinarof were investigated, namely resveratrol, pterostilbene, pinosylvin and its methyl ether. Tapinarof undergoes electrochemical oxidation in a neutral aqueous medium at a potential of around +0.5 V (vs. Ag|AgCl|3M KCl). The anodic reaction of this substance is a proton-dependent irreversible and adsorption-driven process. The pKa value of tapinarof corresponds to 9.19 or 9.93, based on empirical and QM calculation approach, respectively. The oxidation potentials of tapinarof and its analogues correlate well with their HOMO (highest occupied molecular orbital) energy level. The ability to scavenge the DPPH radical decreased in the order trolox ≥ resveratrol > pterostilbene > tapinarof > pinosylvin â‰« pinosylvin methyl ether. It was also confirmed that tapinarof, being a moderate electron donor, is able to scavenge the ABTS radical and inhibit lipid peroxidation. The 4'-OH group plays a pivotal role in antioxidant action of stilbenols. During the stability studies, it was shown that tapinarof is subject to spontaneous degradation under aqueous conditions, and its degradation is accelerated at elevated temperatures and after exposure to UVA (315-399 nm) radiation. In aqueous media at pH 7.4, we observed an ∼50 % degradation of tapinarof after 48 h at laboratory temperature. The main UVA photodegradation processes include dihydroxylation and hydration. In conclusion, the phototoxic effect of tapinarof on a human keratinocytes cell line (HaCaT) was evaluated. Tapinarof exhibited a clear phototoxic effect, similar to phototoxic standard chlorpromazine. The IC50 values of the cytotoxicity and phototoxic effects of tapinarof correspond to 27.6 and 3.7 µM, respectively. The main HaCaT biotransformation products of tapinarof are sulfates and glucuronides.

The protective effect of Artemisia Capillaris Thunb. Extract against UVB-induced apoptosis and inflammation through inhibiting the cGAS/STING pathway.

Exposure to ultraviolet B (UVB) radiation represents a significant environmental threat to human skin. This study investigates the protective mechanism of Artemisia Capillaris Thunb. (AC) extract against UVB-induced apoptosis and inflammation in HaCaT keratinocytes. AC extract demonstrated a significant protective effect, as evidenced by reduced early apoptosis, late apoptosis, and necrosis, as well as decreased apoptotic cell status upon UVB exposure. Additionally, AC extract effectively inhibited UVB-induced DNA damage, as indicated by diminished γ-H2AX foci formation. Restoration of mitochondrial damage and normalization of mitochondrial membrane potential, along with the reduction of intracellular and mitochondrial reactive oxygen species (ROS) levels, were observed with AC extract pre-treatment. The extract also exhibited anti-inflammatory properties, evidenced by the decreased release of IL-1α, IL-6, and PGE2 from keratinocytes. Additional research on the molecular mechanisms uncovered that the AC extract alters the cGAS/STING pathway, suppressing the mRNA (cGAS, STING, IRF3, IRF7 and TBK1) and protein levels (cGAS, STING, IRF3, IRF7 and NF-κB) linked to this particular pathway. The HPLC analysis identified chlorogenic acid and its derivatives as the major components in AC, constituting up to 16.44% of the total chlorogenic acid content. The cGAS/STING signaling pathway was found to be suppressed by chlorogenic acid and its derivatives, as indicated by molecular docking studies and RT-qPCR analysis. This suppression contributes to the protective effects against cell apoptosis and inflammation induced by UVB. To summarize, AC extract, which is abundant in chlorogenic acid and its derivatives, shows potential in protecting keratinocytes from damage caused by UVB by regulating the cGAS/STING signaling pathway.

Effects of Hydroxysafflor Yellow A (HSYA) on UVA-Induced Damage in HaCaT Keratinocytes.

To assess the effects of hydroxysafflor yellow A (HSYA) on ultraviolet A (UVA)-induced damage in HaCaT keratinocytes. HaCaT keratinocytes were UVA-irradiated, and the effects of HSYA on cell viability, reactive oxygen species (ROS) generation, lipid peroxidation, and messenger (m)RNA expression were measured. mRNA expressions of matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, and cyclooxygenase (COX)-2 were determined by a real-time polymerase chain reaction (RT-PCR). UVA exposure led to a decrease in cell viability and an increase in ROS generation in HaCaT keratinocytes. HSYA effectively increased the viability of HaCaT keratinocytes after UVA exposure and protected them from UVA-induced oxidative stress. Moreover, HSYA inhibited expressions of MMP-1, MMP-2, MMP-9, and COX-2 by HaCaT keratinocytes with UVA-induced photodamage. Our results suggest that HSYA can act as a free radical scavenger when keratinocytes are photodamaged. HSYA has the potential to be a skin-protective ingredient against UVA-induced photodamage.

Photoprotective activities of Capsosiphon fulvescens in UVB-induced SKH-1 mice and human keratinocytes.

Capsosiphon fulvescens (CF) is a green alga widely consumed in East Asian countries, particularly in Korea. It has a rich composition of vitamins, minerals, dietary fibers, and bioactive compounds, which contribute to its multiple therapeutic properties. Its application ranges from acting as an antioxidant and anti-inflammatory agent to supporting the skin system. Despite these benefits of CF, the effects and mechanisms of action related to photoaging of the skin have not yet been elucidated. To investigate the photoprotective effects of CF against photoaging, both animal (SKH-1 mouse) and cell models (HaCaT cell line) were used in this study. As a result, administering the CF extract over a period of 10 weeks, which included times of Ultraviolet B (UVB) exposure, significantly reduced erythema and various UVB-induced skin changes, such as wrinkle formation, and the thickening of the epidermis and dermis, as well as alterations in the length and depth of wrinkles. Furthermore, our investigation into CF extract's antiwrinkle properties revealed its efficacy in enhancing skin hydration and collagen content, counteracting the collagen depletion and moisture loss induced by UVB radiation. Also, the fact that the levels of p-ERK, p-p38, and p-JNK proteins went down shows that the CF extract might have a controlling effect on the MAPK signaling pathways. Our findings suggest that CF holds significant potential for preventing photoaging, providing a foundation for the development of functional foods or botanical drugs targeting skin aging and related skin disorders. PRACTICAL APPLICATION: This research proved that Capsosiphon fulvescen, a green alga widely consumed in East Asian countries, provides photoprotective activities against UV-induced skin aging. Therefore, Capsosiphon fulvescen can be utilized as functional foods or botanical drugs targeting skin aging and related skin disorders.

Role of sRNAs protein molecules in extracellular vesicles derived from Lactobacillus plantarum rejuvenate against ultraviolet B-induced photoaging in human keratinocytes.

Ultraviolet B (UVB) radiation accelerates the aging process of skin cells by triggering oxidative stress and inflammatory responses. The aim of this study was to investigate the mechanism of action of sRNAs and protein molecules in the regenerative extracellular vesicles of Lactobacillus plantarum against the UVB-induced photoaging process of human keratinocytes. The extracellular vesicles regenerated by Lactobacillus plantarum were isolated and purified to identify sRNAs and protein components. Human keratinocytes were treated with UVB radiation to simulate the photoaging model. The effects of different concentrations of vesicle extract on cell survival rate, oxidative stress index and inflammatory marker expression were evaluated in control group and treatment group. The results showed that the regenerated extracellular vesicles of L. plantarum significantly improved the survival rate of keratinocytes after UVB radiation, and delayed the aging process of skin cells by reducing oxidative stress and inhibiting inflammatory response.

Comparison of two biological systems used for phototoxicity testing: Cellular and tissue.

The OECD has approved two similar methods for testing the phototoxic potency of chemicals. The first method, OECD 432, is based on the cytotoxicity properties of materials to the mouse 3T3 (clone A31) cell line (fibroblasts) after exposure to light. The second method, OECD 498, is based on the same properties but using reconstructed human epidermis - EpiDerm (stratified keratinocytes). The aim of this study was to compare these two methods using statistical tests (specificity, sensitivity, negative predictive value, positive predictive value and accuracy) and non-statistical characteristics (e.g. price and experimental duration, amount of material, level of complications, cell type, irradiation dose). Both tests were performed according to the relevant guidelines using the same 11 control substances. Higher performance values were observed for OECD 432 in both phototoxic and non-phototoxic classifications. The accuracy of OECD 432 was 90.9%, while that of OECD 498 was 72.7%. OECD 432 was also shorter and less expensive. On the other hand, OECD 498 was less complicated, and used human cells with stratum corneum, which better reflects real skin. This method can also be used with oily substances that are poorly soluble in water. However, both methods are important for testing the phototoxic properties of materials, and can be used alone or in a tiered strategy.