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Skin is a direct target of fine particulate matter (PM2.5), as it is constantly exposed. Herein, we investigate whether Korean red ginseng (KRG) can inhibit PM2.5-induced senescence in skin keratinocytes. PM2.5-treated human keratinocyte cell lines and normal human epidermal keratinocytes showed characteristics of cellular senescence, including flat and enlarged forms; however, KRG suppressed them in both cell types. Moreover, while cells exposed to PM2.5 showed a higher level of p16INK4A expression (a senescence inducer), KRG inhibited its expression. Epigenetically, KRG decreased the expression of the ten-eleven translocation (TET) enzyme, a DNA demethylase induced by PM2.5, and increased the expression of DNA methyltransferases suppressed by PM2.5, resulting in the decreased methylation of the p16INK4A promoter region. Additionally, KRG decreased the expression of mixed-lineage leukemia 1 (MLL1), a histone methyltransferase, and histone acetyltransferase 1 (HAT1) induced by PM2.5. Contrastingly, KRG increased the expression of the enhancer of zeste homolog 2, a histone methyltransferase, and histone deacetyltransferase 1 reduced by PM2.5. Furthermore, KRG decreased TET1, MLL1, and HAT1 binding to the p16INK4A promoter, corresponding with the decreased mRNA expression of p16INK4A. These results suggest that KRG exerts protection against the PM2.5-induced senescence of skin keratinocytes via the epigenetic regulation of p16INK4A.

Cellular senescence can be activated by several stimuli, including ultraviolet radiation and air pollutants. This study aimed to evaluate the protective effect of marine algae compound 3-bromo-4,5-dihydroxybenzaldehyde (3-BDB) on particulate matter 2.5 (PM2.5)-induced skin cell damage in vitro and in vivo. The human HaCaT keratinocyte was pre-treated with 3-BDB and then with PM2.5. PM2.5-induced reactive oxygen species (ROS) generation, lipid peroxidation, mitochondrial dysfunction, DNA damage, cell cycle arrest, apoptotic protein expression, and cellular senescence were measured using confocal microscopy, flow cytometry, and Western blot. The present study exhibited PM2.5-generated ROS, DNA damage, inflammation, and senescence. However, 3-BDB ameliorated PM2.5-induced ROS generation, mitochondria dysfunction, and DNA damage. Furthermore, 3-BDB reversed the PM2.5-induced cell cycle arrest and apoptosis, reduced cellular inflammation, and mitigated cellular senescence in vitro and in vivo. Moreover, the mitogen-activated protein kinase signaling pathway and activator protein 1 activated by PM2.5 were inhibited by 3-BDB. Thus, 3-BDB suppressed skin damage induced by PM2.5.

Particulate matter 2.5 (PM2.5) poses a serious threat to human health and is responsible for respiratory disorders, cardiovascular diseases, and skin disorders. 3-Bromo-4,5-dihydroxybenzaldehyde (3-BDB), abundant in marine red algae, exhibits anti-inflammatory, antioxidant, and antidiabetic activities. In this study, we investigated the protective mechanisms of 3-BDB against PM2.5-induced cell cycle arrest and autophagy in human keratinocytes. Intracellular reactive oxygen species generation, DNA damage, cell cycle arrest, intracellular Ca2+ level, and autophagy activation were tested. 3-BDB was found to restore cell proliferation and viability which were reduced by PM2.5. Furthermore, 3-BDB reduced PM2.5- induced reactive oxygen species levels, DNA damage, and attenuated cell cycle arrest. Moreover, 3-BDB ameliorated the PM2.5-induced increases in cellular Ca2+ level and autophagy activation. While PM2.5 treatment reduced cell growth and viability, these were restored by the treatment with the autophagy inhibitor bafilomycin A1 or 3-BDB. The findings indicate that 3-BDB ameliorates skin cell death caused by PM2.5 via inhibiting cell cycle arrest and autophagy. Hence, 3-BDB can be exploited as a preventive/therapeutic agent for PM2.5-induced skin impairment. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are associated with neuronal cell death through apoptosis. Apoptosis is tightly associated with the overproduction of reactive oxygen species (ROS), and high glucose levels contribute to higher oxidative stress in diabetic patients. Hesperidin, a natural active compound, has been reported to scavenge free radicals. Only a few studies have explored the protective effects of hesperidin against high glucose−induced apoptosis in SH−SY5Y neuronal cells. Glucose stimulated neuronal cells to generate excessive ROS and caused DNA damage. In addition, glucose triggered endoplasmic reticulum stress and upregulated cytoplasmic as well as mitochondrial calcium levels. Hesperidin inhibited glucose−induced ROS production and mitigated the associated DNA damage and endoplasmic reticulum stress. The downregulation of antiapoptotic protein Bcl−2 following glucose treatment was reversed by a hesperidin treatment. Furthermore, hesperidin repressed the glucose−induced Bcl−2−associated X protein, cleaved caspase−9, and cleaved caspase−3. Hesperidin also suppressed the glucose−induced phosphorylation of extracellular signal−regulated kinase and c−Jun N−terminal kinase. The current results confirmed that hesperidin could protect neuronal cells against glucose−induced ROS. Mechanistically, hesperidin was shown to promote cell viability via attenuation of the mitogen−activated protein kinase signaling pathway.

Ginseng (Panax ginseng Meyer) has been used in East Asian traditional medicine for a long time. Korean red ginseng (KRG) is effective against several disorders, including cancer. The cytotoxic effects of KRG extract in terms of autophagy- and apoptosis-mediated cell death and its mechanisms were investigated using human colorectal cancer lines. KRG induced autophagy-mediated cell death with enhanced expression of Atg5, Beclin-1, and LC3, and formed characteristic vacuoles in HCT-116 and SNU-1033 cells. An autophagy inhibitor prevented cell death induced by KRG. KRG generated mitochondrial reactive oxygen species (ROS); antioxidant countered this effect and decreased autophagy. KRG caused apoptotic cell death by increasing apoptotic cells and sub-G1 cells, and by activating caspases. A caspase inhibitor suppressed cell death induced by KRG. KRG increased phospho-Bcl-2 expression, but decreased Bcl-2 expression. Moreover, interaction of Bcl-2 with Beclin-1 was attenuated by KRG. Ginsenoside Rg2 was the most effective ginsenoside responsible for KRG-induced autophagy- and apoptosis-mediated cell death. KRG induced autophagy- and apoptosis-mediated cell death via mitochondrial ROS generation, and thus its administration may inhibit colon carcinogenesis.

Cancer: Cell-killing plant compound exerts antioxidant effects A molecule found in fruits, vegetables and herbs helps kill colon cancer cells by activating a master regulator of detoxifying enzymes. Jin Won Hyun from Jeju National University School of Medicine in South Korea and colleagues treated human colon cancer cells with luteolin, a molecule that occurs naturally in many food plants. They showed that luteolin increased the levels of proteins involved in cell death and antioxidant responses by causing DNA-modifying enzymes to strip suppressive chemical markers off the gene encoding Nrf2, a protein that regulates antioxidant effects. Nrf2 levels subsequently increased and the protein interacted with the tumor suppressor p53 to facilitate destruction of the colon cancer cells. The findings offer a mechanistic basis for using luteolin to help prevent and treat cancer.

Skin is exposed to several harmful environmental effects including ultraviolet B (UVB) and air pollution, the most harmful component of which is particulate matter (PM). Damaging effects of UVB and PM include the generation of cellular reactive oxygen species (ROS), lipid peroxidation, protein carbonylation, DNA damage, and apoptosis. A compound with the potential to protect the skin against environmental oxidative damage is 3,4-dicaffeoylquinic acid (DQA), an antioxidant found in plant matter, including the coffee bean. In this study, we investigated the protective effects of DQA against UVB- and PM-induced oxidative cell damage in cultured human keratinocytes (HaCaT). We demonstrated that UVB, and PM with a diameter

Numerous epidemiological studies have reported that particulate matter 2.5 (PM2.5) causes skin aging and skin inflammation and impairs skin homeostasis. Hesperidin, a bioflavonoid that is abundant in citrus species, reportedly has anti-inflammatory properties. In this study, we evaluated the cytoprotective effect of hesperidin against PM2.5-mediated damage in a human skin cell line (HaCaT). Hesperidin reduced PM2.5-induced intracellular reactive oxygen species (ROS) generation and oxidative cellular/organelle damage. PM2.5 increased the proportion of acridine orange-positive cells, levels of autophagy-related proteins, beclin-1 and microtubule-associated protein light chain 3, and apoptosis-related proteins, B-cell lymphoma-2-associated X protein, cleaved caspase-3, and cleaved caspase-9. However, hesperidin ameliorated PM2.5-induced autophagy and apoptosis. PM2.5 promoted cellular apoptosis via mitogen-activated protein kinase (MAPK) activation by promoting the phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38. The MAPK inhibitors U0126, SP600125, and SB203580 along with hesperidin exerted a protective effect against PM2.5-induced cellular apoptosis. Furthermore, hesperidin restored PM2.5-mediated reduction in cell viability via Akt activation; this was also confirmed using LY294002 (a phosphoinositide 3-kinase inhibitor). Overall, hesperidin shows therapeutic potential against PM2.5-induced skin damage by mitigating excessive ROS accumulation, autophagy, and apoptosis.

Particulate matter 2.5 (PM2.5) exposure can trigger adverse health outcomes in the human skin, such as skin aging, wrinkles, pigment spots, and atopic dermatitis. PM2.5 is associated with mitochondrial damage and the generation of reactive oxygen species (ROS). Hesperidin is a bioflavonoid that exhibits antioxidant and anti-inflammatory properties. This study aimed to determine the mechanism underlying the protective effect of hesperidin on human HaCaT keratinocytes against PM2.5-induced mitochondrial damage, cell cycle arrest, and cellular senescence. Human HaCaT keratinocytes were pre-treated with hesperidin and then treated with PM2.5. Hesperidin attenuated PM2.5-induced mitochondrial and DNA damage, G0/G1 cell cycle arrest, and SA-βGal activity, the protein levels of cell cycle regulators, and matrix metalloproteinases (MMPs). Moreover, treatment with a specific c-Jun N-terminal kinase (JNK) inhibitor, SP600125, along with hesperidin markedly restored PM2.5-induced cell cycle arrest and cellular senescence. In addition, hesperidin significantly reduced the activation of MMPs, including MMP-1, MMP-2, and MMP-9, by inhibiting the activation of activator protein 1. In conclusion, hesperidin ameliorates PM2.5-induced mitochondrial damage, cell cycle arrest, and cellular senescence in human HaCaT keratinocytes via the ROS/JNK pathway.

We have previously shown that non-thermal dielectric-barrier discharge (DBD) plasma induces the generation of reactive oxygen species (ROS) in cells; however, the underlying mechanism has not been elucidated. This study aimed to identify the mechanisms through which DBD plasma induces the expression of NADPH oxidase (NOX) family members by epigenetic modification in human keratinocytes (HaCaT). Cell exposure to DBD plasma in 10% oxygen and 90% argon resulted in the generation of ROS, triggering oxidative stress that manifested in various forms, including lipid membrane peroxidation, DNA base modification, and protein carbonylation. DBD plasma upregulated the expression of NOX1, NOX5, and DUOX2 at the mRNA and protein levels; and siRNAs targeting NOX1, NOX5, and DUOX2 attenuated the generation of DBD plasma-induced ROS. DBD plasma upregulated the transcriptional activators TET1, MLL1, and HAT1 and downregulated the transcriptional repressors DNMT1, EZH2, and HDAC1. Additionally, DBD plasma increased the binding of transcriptional activators and decreased the binding of transcriptional repressors to the DUOX2 promoter. Methyl-specific polymerase chain reaction and bisulfite sequencing indicated that DBD plasma decreased methylation at the DUOX2 promoter. These results suggest that DBD plasma induces ROS generation by enhancing the expression of the NOX system through epigenetic DNA and histone modifications.

This study investigated the protective effect of mackerel-derived fermented fish oil (FFO) against UVB radiation-induced oxidative stress in human HaCaT keratinocytes and mouse skin tissue. FFO treatment scavenged UVB-induced intracellular reactive oxygen species and attenuated oxidative modifications including lipid peroxidation, protein carbonylation, and DNA damage. FFO treatment reduced UVB-induced apoptosis by reducing DNA fragmentation, caspase activation, and proapoptotic protein expression. UVB radiation activated phospho-extracellular signal-regulated kinase, phospho-c-Jun N-terminal kinase, and phospho-p38, whereas their specific inhibitors with FFO treatment abrogated the cell viability and apoptosis increased by UVB irradiation. FFO was more cytoprotective than docosahexaenoic acid, the main component of fish oil, against UVB exposure. Furthermore, the cytoprotective effect of FFO was evident in both UVB-exposed HaCaT cell and mouse models. Overall, these results demonstrate that FFO protects the skin against UVB-induced oxidative stress through antioxidant effects. FFO has the potential for development as a functional food against UVB-induced skin damage.

The therapeutic benefits offered by 5-fluorouracil (5-FU) are limited because of the acquisition of drug resistance, the main cause of treatment failure and metastasis. The ability of the cancer cells to undergo epithelial-mesenchymal transition (EMT) contributes significantly to cancer metastatic potential and chemo-resistance. However, the underlying molecular mechanisms of 5-FU-resistance have remained elusive. Here, we show that reactive oxygen species (ROS), produced by dual oxidase 2 (DUOX2), promote 5-FU-induced EMT. First, we showed that 5-FU–resistant SNUC5 colon cancer cells (SNUC5/FUR cells) undergo EMT by analyzing the expression of EMT markers such as N-cadherin, vimentin and E-cadherin. In addition, we found that the resistant cells expressed higher levels of Snail, Slug, Twist and Zeb1, which are all critical EMT regulators and had enhanced migratory and invasive capabilities. Furthermore, SNUC5/FUR cells had increased level of DUOX2, resulting in increased ROS level. This effect was due to the enhanced binding of the ten eleven translocation 1 (TET1) demethylase to the DUOX2 promoter in the SNUC5/FUR cells. Importantly, silencing of TET1 reversed the effects of 5-FU on the cells. Finally, the antioxidant N-acetylcysteine attenuated the effects of 5-FU on EMT and metastasis. Our study demonstrates the existence of a TET1/DUOX2/ROS/EMT axis that could play a role in colon cancer chemo-resistance and the aggressiveness of this cancer. Keywords: 5-FU resistance, DNA demethylase, DUOX2, Epithelial-mesenchymal transition, Metastasis

Particulate matter (PM) increases levels of pro-inflammatory cytokines, but its effects on the skin remain largely unknown. We investigated the signal transduction pathway and epigenetic regulatory mechanisms underlying cellular inflammation induced by PM with a diameter of ≤ 2.5 (PM2.5) in vitro and in vivo. PM2.5-treated skin keratinocytes produced various inflammatory cytokines, including IL-6. The binding of PM2.5 to TLR5 initiated intracellular signaling through MyD88, and led to the translocation of NFκB to the nucleus, where it bound the NFκB site within IL-6 promoter. Furthermore, PM2.5 induced a direct interaction between TLR5 and NOX4, and in turn induced the production of ROS and activated NFκB-IL-6 downstream, which was prevented by siRNA-mediated knockdown of NOX4 or antioxidant treatment. Furthermore, expression of TLR5, MyD88, NOX4, phospho-NFκB, and IL-6 was increased in skin tissue of PM2.5-treated flaky tail mice. PM2.5-induced increased transcription of IL-6 was regulated via DNA methylation and histone methylation by epigenetic modification; the binding of DNA demethylase and histone methyltransferase to the IL-6 promoter regions resulted in increased IL-6 mRNA expression. Our findings provide deep insight into the pathogenesis of PM2.5 exposure and can be used as a therapeutic strategy to treat inflammatory skin diseases caused by PM2.5 exposure. Keywords: Particulate matter, Interleukin-6, Reactive oxygen species, Toll like receptor, Epigenetic modification

We investigated the protective properties of diphlorethohydroxycarmalol (DPHC), a phlorotannin, against ultraviolet B (UVB) radiation-induced cyclobutane pyrimidine dimers (CPDs) in HaCaT human keratinocytes. The nucleotide excision repair (NER) system is the pathway by which cells identify and repair bulky, helix-distorting DNA lesions such as ultraviolet (UV) radiation-induced CPDs and 6-4 photoproducts. CPDs levels were elevated in UVB-exposed cells; however, this increase was reduced by DPHC. Expression levels of xeroderma pigmentosum complementation group C (XPC) and excision repair cross-complementing 1 (ERCC1), which are essential components of the NER pathway, were induced in DPHC-treated cells. Expression of XPC and ERCC1 were reduced following UVB exposure, whereas DPHC treatment partially restored the levels of both proteins. DPHC also increased expression of transcription factor specificity protein 1 (SP1) and sirtuin 1, an up-regulator of XPC, in UVB-exposed cells. DPHC restored binding of the SP1 to the XPC promoter, which is reduced in UVB-exposed cells. These results indicate that DPHC can protect cells against UVB-induced DNA damage by inducing the NER system.

This study investigated the protective mechanisms of triphlorethol-A, isolated from Ecklonia cava, against oxidative stress-induced DNA base damage, especially 8-oxoguanine (8-oxoG), in Chinese hamster lung fibroblast V79-4 cells. 8-Oxoguanine DNA glycosylase-1 (OGG1) plays an important role in the removal of 8-oxoG during the cellular response to DNA base damage. Triphlorethol-A significantly decreased the levels of 8-oxoG induced by H2O2, and this correlated with increases in OGG1 mRNA and OGG1 protein levels. Furthermore, siOGG1-transfected cell attenuated the protective effect of triphlorethol-A against H2O2 treatment. Nuclear factor erythroid 2–related factor 2 (Nrf2) is a transcription factor for OGG1, and Nrf2 combines with small Maf proteins in the nucleus to bind to antioxidant response elements (ARE) in the upstream promoter region of the OGG1 gene. Triphlorethol-A restored the expression of nuclear Nrf2, small Maf protein, and the Nrf2-Maf complex, all of which were reduced by oxidative stress. Furthermore, triphlorethol-A increased Nrf2 binding to ARE sequences and the resulting OGG1 promoter activity, both of which were also reduced by oxidative stress. The levels of the phosphorylated forms of Akt kinase, downstream of phosphatidylinositol 3-kinase (PI3K), and Erk, which are regulators of OGG1, were sharply decreased by oxidative stress, but these decreases were prevented by triphlorethol-A. Specific PI3K, Akt, and Erk inhibitors abolished the cytoprotective effects of triphlorethol-A, suggesting that OGG1 induction by triphlorethol-A involves the PI3K/Akt and Erk pathways. Taken together, these data indicate that by activating the DNA repair system, triphlorethol-A exerts protective effects against DNA base damage induced by oxidative stress.

Fucoxanthin, a natural carotenoid, is abundant in seaweed with antioxidant properties. This study investigated the role of fucoxanthin in the induction of antioxidant enzymes involved in the synthesis of reduced glutathione (GSH), synthesized by glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS), via Akt/nuclear factor-erythroid 2-related (Nrf2) pathway in human keratinocytes (HaCaT) and elucidated the underlying mechanism. Fucoxanthin treatment increased the mRNA and protein levels of GCLC and GSS in HaCaT cells. In addition, fucoxanthin treatment promoted the nuclear translocation and phosphorylation of Nrf2, a transcription factor for the genes encoding GCLC and GSS. Chromatin immune-precipitation and luciferase reporter gene assays revealed that fucoxanthin treatment increased the binding of Nrf2 to the antioxidant response element (ARE) sequence and transcriptional activity of Nrf2. Fucoxanthin treatment increased phosphorylation of Akt (active form), an up-regulator of Nrf2 and exposure to LY294002, a phosphoinositide 3-kinase (PI3K)/Akt inhibitor, suppressed the fucoxanthin-induced activation of Akt, Nrf2, resulting in decreased GCLC and GSS expression. In accordance with the effects on GCLC and GSS expression, fucoxanthin induced the level of GSH. In addition, fucoxanthin treatment recovered the level of GSH reduced by ultraviolet B irradiation. Taken together, these findings suggest that fucoxanthin treatment augments cellular antioxidant defense by inducing Nrf2-driven expression of enzymes involved in GSH synthesis via PI3K/Akt signaling.

The prevalence of fine particulate matter-induced harm to the human body is increasing daily. The aim of this study was to elucidate the mechanism by which particulate matter 2.5 (PM2.5) induces damage in human HaCaT keratinocytes and normal human dermal fibroblasts, and to evaluate the preventive capacity of the ginsenoside Rb1. PM2.5 induced oxidative stress by increasing the production of reactive oxygen species, leading to DNA damage, lipid peroxidation, and protein carbonylation; this effect was inhibited by ginsenoside Rb1. Through gene silencing of endoplasmic reticulum (ER) stress-related genes such as PERK, IRE1, ATF, and CHOP, and through the use of the ER stress inhibitor tauroursodeoxycholic acid (TUDCA), it was demonstrated that PM2.5-induced ER stress also causes apoptosis and ultimately leads to cell death; however, this phenomenon was reversed by ginsenoside Rb1. We also found that TUDCA partially restored the production of ATP that was inhibited by PM2.5, and its recovery ability was significantly higher than that of ginsenoside Rb1, indicating that the process of ER stress leading to cell damage may also occur via the mitochondrial pathway. We concluded that ER stress acts alone or via the mitochondrial pathway in the induction of cell damage by PM2.5, and that ginsenoside Rb1 blocks this process. Ginsenoside Rb1 shows potential for use in skin care products to protect the skin against damage by fine particles.

Toxicity of particulate matter (PM) towards the epidermis has been well established in many epidemiological studies. It is manifested in cancer, aging, and skin damage. In this study, we aimed to show the mechanism underlying the protective effects of eckol, a phlorotannin isolated from brown seaweed, on human HaCaT keratinocytes against PM2.5-induced cell damage. First, to elucidate the underlying mechanism of toxicity of PM2.5, we checked the reactive oxygen species (ROS) level, which contributed significantly to cell damage. Experimental data indicate that excessive ROS caused damage to lipids, proteins, and DNA and induced mitochondrial dysfunction. Furthermore, eckol (30 μM) decreased ROS generation, ensuring the stability of molecules, and maintaining a steady mitochondrial state. The western blot analysis showed that PM2.5 promoted apoptosis-related protein levels and activated MAPK signaling pathway, whereas eckol protected cells from apoptosis by inhibiting MAPK signaling pathway. This was further reinforced by detailed investigations using MAPK inhibitors. Thus, our results demonstrated that inhibition of PM2.5-induced cell apoptosis by eckol was through MAPK signaling pathway. In conclusion, eckol could protect skin HaCaT cells from PM2.5-induced apoptosis via inhibiting ROS generation.

In this study, we aimed to illustrate the potential bio-effects of 3-bromo-4,5-dihydroxybenzaldehyde (3-BDB) on the antioxidant/cytoprotective enzyme heme oxygenase-1 (HO-1) in keratinocytes. The antioxidant effects of 3-BDB were examined via reverse transcription PCR, Western blotting, HO-1 activity assay, and immunocytochemistry. Chromatin immunoprecipitation analysis was performed to test for nuclear factor erythroid 2-related factor 2 (Nrf2) binding to the antioxidant response element of the HO-1 promoter. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the cytoprotective effects of 3-BDB were mediated by the activation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB, Akt) signaling. Moreover, 3-BDB induced the phosphorylation of ERK and Akt, while inhibitors of ERK and Akt abrogated the 3-BDB-enhanced levels of HO-1 and Nrf2. Finally, 3-BDB protected cells from H2O2- and UVB-induced oxidative damage. This 3-BDB-mediated cytoprotection was suppressed by inhibitors of HO-1, ERK, and Akt. The present results indicate that 3-BDB activated Nrf2 signaling cascades in keratinocytes, which was mediated by ERK and Akt, upregulated HO-1, and induced cytoprotective effects against oxidative stress.

Horse oil products have been used in skin care for a long time in traditional medicine, but the biological effects of horse oil on the skin remain unclear. This study was conducted to evaluate the protective effect of horse oil on ultraviolet B (UVB)-induced oxidative stress in human HaCaT keratinocytes. Horse oil significantly reduced UVB-induced intracellular reactive oxygen species and intracellular oxidative damage to lipids, proteins, and DNA. Horse oil absorbed light in the UVB range of the electromagnetic spectrum and suppressed the generation of cyclobutane pyrimidine dimers, a photoproduct of UVB irradiation. Western blotting showed that horse oil increased the UVB-induced Bcl-2/Bax ratio, inhibited mitochondria-mediated apoptosis and matrix metalloproteinase expression, and altered mitogen-activated protein kinase signaling-related proteins. These effects were conferred by increased phosphorylation of extracellular signal-regulated kinase 1/2 and decreased phosphorylation of p38 and c-Jun N-terminal kinase 1/2. Additionally, horse oil reduced UVB-induced binding of activator protein 1 to the matrix metalloproteinase-1 promoter site. These results indicate that horse oil protects human HaCaT keratinocytes from UVB-induced oxidative stress by absorbing UVB radiation and removing reactive oxygen species, thereby protecting cells from structural damage and preventing cell death and aging. In conclusion, horse oil is a potential skin protectant against skin damage involving oxidative stress.

The skin, the largest organ in humans, is exposed to major sources of outdoor air pollution, such as fine particulate matter with a diameter ≤ 2.5 µm (PM2.5). Diphlorethohydroxycarmalol (DPHC), a marine-based compound, possesses multiple activities including antioxidant effect. In the present study, we evaluated the protective effect of DPHC on PM2.5-induced skin cell damage and elucidated the underlying mechanisms in vitro and in vivo. The results showed that DPHC blocked PM2.5-induced reactive oxygen species generation in human keratinocytes. In addition, DPHC protected cells against PM2.5-induced DNA damage, endoplasmic reticulum stress, and autophagy. HR-1 hairless mice exposed to PM2.5 showed lipid peroxidation, protein carbonylation, and increased epidermal height, which were inhibited by DPHC. Moreover, PM2.5 induced apoptosis and mitogen-activated protein kinase (MAPK) protein expression; however, these changes were attenuated by DPHC. MAPK inhibitors were used to elucidate the molecular mechanisms underlying these actions, and the results demonstrated that MAPK signaling pathway may play a key role in PM2.5-induced skin damage.

Skin is exposed to various harmful environmental factors such as air pollution, which includes different types of particulate matter (PM). Atmospheric PM has harmful effects on humans through increasing the generation of reactive oxygen species (ROS), which have been reported to promote skin aging via the induction of matrix metalloproteinases (MMPs), which in turn can cause the degradation of collagen. In this study, we investigated the effect of fermented fish oil (FFO) derived from mackerel on fine PM (particles with a diameter < 2.5 µm: PM2.5)-induced skin aging in human keratinocytes. We found that FFO inhibited the PM2.5-induced generation of intracellular ROS and MMPs, including MMP-1, MMP-2, and MMP-9. In addition, FFO significantly abrogated the elevation of intracellular Ca2+ levels in PM2.5-treated cells and was also found to block the PM2.5-induced mitogen-activated protein kinase/activator protein 1 (MAPK/AP-1) pathway. In conclusion, FFO has an anti-aging effect on PM2.5-induced aging in human keratinocytes.

The present study investigated the photoprotective properties of an ethanol extract derived from the red alga Bonnemaisonia hamifera against ultraviolet B (UVB)-induced cell damage in human HaCaT keratinocytes. The Bonnemaisonia hamifera ethanol extract (BHE) scavenged the superoxide anion generated by the xanthine/xanthine oxidase system and the hydroxyl radical generated by the Fenton reaction (FeSO4 + H2O2), both of which were detected by using electron spin resonance spectrometry. In addition, BHE exhibited scavenging activity against the 1,1-diphenyl-2-picrylhydrazyl radical and intracellular reactive oxygen species (ROS) that were induced by either hydrogen peroxide or UVB radiation. BHE reduced UVB-induced apoptosis, as shown by decreased apoptotic body formation and DNA fragmentation. BHE also attenuated DNA damage and the elevated levels of 8-isoprostane and protein carbonyls resulting from UVB-mediated oxidative stress. Furthermore, BHE absorbed electromagnetic radiation in the UVB range (280–320 nm). These results suggest that BHE protects human HaCaT keratinocytes against UVB-induced oxidative damage by scavenging ROS and absorbing UVB photons, thereby reducing injury to cellular components.

The aim of this study was to investigate the cytoprotective properties of the ethyl acetate fraction of Sargassum muticum (SME) against ultraviolet B (UVB)-induced cell damage in human keratinocytes (HaCaT cells). SME exhibited scavenging activity toward the 1,1-diphenyl-2-picrylhydrazyl radicals and hydrogen peroxide (H2O2) and UVB-induced intracellular reactive oxygen species (ROS). SME also scavenged the hydroxyl radicals generated by the Fenton reaction (FeSO4 + H2O2), which was detected using electron spin resonance spectrometry. In addition, SME decreased the level of lipid peroxidation that was increased by UVB radiation, and restored the level of protein expression and the activities of antioxidant enzymes that were decreased by UVB radiation. Furthermore, SME reduced UVB-induced apoptosis as shown by decreased DNA fragmentation and numbers of apoptotic bodies. These results suggest that SME protects human keratinocytes against UVB-induced oxidative stress by enhancing antioxidant activity in cells, thereby inhibiting apoptosis.

Recently, we demonstrated that butin (7,3′,4′-trihydroxydihydroflavone) protected cells against hydrogen peroxide (H2O2)-induced apoptosis by: (1) scavenging reactive oxygen species (ROS), activating antioxidant enzymes such superoxide dismutase and catalase; (2) decreasing oxidative stress-induced 8-hydroxy-2'-deoxyguanosine levels via activation of oxoguanine glycosylase 1, and (3), reducing oxidative stress-induced mitochondrial dysfunction. The objective of this study was to determine the cytoprotective effects of butin on oxidative stress-induced mitochondria-dependent apoptosis, and possible mechanisms involved. Butin significantly reduced H2O2-induced loss of mitochondrial membrane potential as determined by confocal image analysis and flow cytometry, alterations in Bcl-2 family proteins such as decrease in Bcl-2 expression and increase in Bax and phospho Bcl-2 expression, release of cytochrome c from mitochondria into the cytosol and activation of caspases 9 and 3. Furthermore, the anti-apoptotic effect of butin was exerted via inhibition of mitogen-activated protein kinase kinase-4, c-Jun NH2-terminal kinase (JNK) and activator protein-1 cascades induced by H2O2 treatment. Finally, butin exhibited protective effects against H2O2-induced apoptosis, as demonstrated by decreased apoptotic bodies, sub-G1 hypodiploid cells and DNA fragmentation. Taken together, the protective effects of butin against H2O2-induced apoptosis were exerted via blockade of membrane potential depolarization, inhibition of the JNK pathway and mitochondria-involved caspase-dependent apoptotic pathway

The aim of this study was to investigate the antioxidant properties of the ethanol extract of the flower of Camellia japonica (Camellia extract). Camellia extract exhibited 1,1-diphenyl-2-picrylhydrazyl radical and intracellular reactive oxygen species (ROS) scavenging activity in human HaCaT keratinocytes. In addition, Camellia extract scavenged superoxide anion generated by xanthine/xanthine oxidase and hydroxyl radical generated by the Fenton reaction (FeSO4 + H2O2) in a cell-free system, which was detected by electron spin resonance spectrometry. Furthermore, Camellia extract increased the protein expressions and activity of cellular antioxidant enzymes, such as superoxide dismutase, catalase and glutathione peroxidase. These results suggest that Camellia extract exhibits antioxidant properties by scavenging ROS and enhancing antioxidant enzymes. Camellia extract contained quercetin, quercetin-3-O-glucoside, quercitrin and kaempferol, which are antioxidant compounds.

Recently, we demonstrated that myricetin exhibits cytoprotective effects against H2O2-induced cell damage via its antioxidant properties. In the present study, myricetin was found to inhibit H2O2-induced apoptosis in Chinese hamster lung fibroblast (V79-4) cells, as shown by decreased apoptotic bodies, nuclear fragmentation, sub-G1 cell population, and disruption of mitochondrial membrane potential (Dym), which are increased in H2O2-treated cells. Western blot data showed that in H2O2-treated cells, myricetin increased the level of Bcl-2, which is an anti-apoptotic factor, and decreased the levels of Bax, active caspase-9 and -3, which are pro-apoptotic factors. And myricetin inhibited release of cytochrome c from mitochondria to cytosol in H2O2-treated cells. Myricetin-induced survival correlated with Akt activity, and the rescue of cells by myricetin treatment against H2O2-induced apoptosis was inhibited by the specific PI3K (phosphoinositol-3-kinase) inhibitor. Myricetin-mediated survival also inhibited the activation of p38 mitogen activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), which are members of MAPK. Our studies suggest that myricetin prevents oxidative stress-induced apoptosis via regulation of PI3K/Akt and MAPK signaling pathways.

A natural bromophenol found in seaweeds, 3-bromo-4,5-dihydroxybenzaldehyde (BDB), has been shown to possess antioxidant effects. This study aimed to investigate the mechanism by which BDB protects skin cells subjected to oxidative stress. The effect of BDB on the protein and mRNA levels of glutathione-related enzymes and the cell survival of human keratinocytes (HaCaT cells) was investigated. BDB treatment increased the protein and mRNA levels of glutathione synthesizing enzymes and enhanced the production of reduced glutathione in HaCaT cells. Furthermore, BDB activated NF-E2-related factor 2 (Nrf2) and promoted its localization into the nucleus by phosphorylating its up-stream signaling proteins, extracellular signal–regulated kinase and protein kinase B. Thus, BDB increased the production of reduced glutathione and established cellular protection against oxidative stress via an Nrf2-mediated pathway.

Skin exposure to ultraviolet B (UVB) irradiation leads to the generation of reactive oxygen species (ROS). Excessive ROS cause aging of the skin via basement membrane/extracellular matrix degradation by matrix metalloproteinases (MMPs). We recently demonstrated that 3-bromo-4,5-dihydroxybenzaldehyde (BDB), a natural compound of red algae, had a photo-protective effect against UVB-induced oxidative stress in human keratinocytes. The present study focused on the effect of BDB on UVB-irradiated photo-aging in HaCaT keratinocytes and the underlying mechanism. BDB significantly impeded MMP-1 activation and expression, and abrogated the activation of mitogen-activated protein kinases and intracellular Ca2+ level in UVB-irradiated HaCaT cells. Moreover, BDB decreased the expression levels of c-Fos and phospho-c-Jun and the binding of activator protein-1 to the MMP-1 promoter induced by UVB irradiation. These results offer evidence that BDB is potentially useful for the prevention of UVB-irradiated skin damage.

The authors want to change Figure 1 of the paper published in IJMS [1]. In Figure 1, 5-position of OH was at 6-position. Therefore, Figure 1 is revised as follows. The authors would like to apologize for any inconvenience caused to the readers by this change.[...]