Naringenin Induces Cellular Apoptosis in Melanoma Cells via Intracellular ROS Generation.

BACKGROUND/AIM: Melanoma is a prevalent malignant tumor that arises from melanocytes. The treatment of malignant melanoma has become challenging due to the development of drug resistance. It is, therefore, imperative to identify novel therapeutic drug candidates for controlling malignant melanoma. Naringenin is a flavonoid abundant in oranges and other citrus fruits and recognized for its numerous medicinal benefits. The objective of the study was to assess the anti-carcinogenic potential of naringenin by evaluating its ability to regulate the cellular production of reactive oxygen species (ROS) and its effect on mitochondrial function and apoptosis in melanoma cells. MATERIALS AND METHODS: Cell viability, intracellular ROS levels, cell apoptosis, and mitochondrial functions were evaluated. RESULTS: Naringenin decreased melanoma cell viability and triggered generation of ROS, leading to cell apoptosis. In addition, it stimulated mitochondrial damage in melanoma cells by elevating the levels of Ca2+ and ROS in the mitochondria and decreasing cellular ATP. Naringenin stimulated the expression of proapoptotic proteins, including phospho p53, B-cell lymphoma-2 (Bcl-2)-associated X protein, cleaved caspase-3, and cleaved caspase-9, in melanoma cells in a time-dependent manner. Furthermore, it reduced the expression of the anti-apoptotic protein Bcl-2. Naringenin triggered cell apoptosis by phosphorylating c-Jun N-terminal kinase and stimulating cellular autophagy. CONCLUSION: Naringenin caused oxidative stress and mitochondrial damage, and activated autophagy in melanoma cells, leading to cell apoptosis. These findings indicate the potential of naringenin as a new therapeutic candidate for melanoma.

Correction: Kang et al. Anticolon Cancer Effect of Korean Red Ginseng via Autophagy- and Apoptosis-Mediated Cell Death. Nutrients 2022, 14, 3558.

In the original publication [...].

3-Bromo-4,5-dihydroxybenzaldehyde Protects Keratinocytes from Particulate Matter 2.5-Induced Damages.

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.

Anticolon Cancer Effect of Korean Red Ginseng via Autophagy- and Apoptosis-Mediated Cell Death.

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.

Hesperidin Protects SH-SY5Y Neuronal Cells against High Glucose-Induced Apoptosis via Regulation of MAPK Signaling.

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.

Hesperidin Exhibits Protective Effects against PM2.5-Mediated Mitochondrial Damage, Cell Cycle Arrest, and Cellular Senescence in Human HaCaT Keratinocytes.

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-ßGal 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.

Hesperidin Protects Human HaCaT Keratinocytes from Particulate Matter 2.5-Induced Apoptosis via the Inhibition of Oxidative Stress and Autophagy.

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.

Comparative Study of Autophagy in Oxaliplatin-Sensitive and Resistant SNU-C5 Colon Cancer Cells.

Few studies have evaluated the role of autophagy in the development of oxaliplatin (OXT) resistance in colon cancer cells. In this study, we compared the role of autophagy between SNU-C5 colon cancer cells and OXT-resistant SNU-C5 (SNU-C5/OXTR) cells. At the same concentration of OXT, the cytotoxicity of OXT or apoptosis was significantly reduced in SNU-C5/OXTR cells compared with that in SNU-C5 cells. Compared with SNU-C5 cells, SNU-C5/OXTR cells exhibited low levels of autophagy. The expression level of important autophagy proteins, such as autophagy-related protein 5 (Atg5), beclin-1, Atg7, microtubule-associated proteins 1A/1B light chain 3B I (LC3-I), and LC3-II, was significantly lower in SNU-C5/OXTR cells than that in SNU-C5 cells. The expression level of the autophagy-essential protein p62 was also lower in SNU-C5/OXTR cells than in SNU-C5 cells. In SNUC5/ OXTR cells, the production of intracellular reactive oxygen species (ROS) was significantly higher than that in SNU-C5 cells, and treatment with the ROS scavenger N-acetylcysteine restored the reduced autophagy levels. Furthermore, the expression of antioxidant-related nuclear factor erythroid 2-related factor 2 transcription factor, heme oxygenase-1, and Cu/Zn superoxide dismutase were also significantly increased in SNU-C5/OXTR cells. These findings suggest that autophagy is significantly reduced in SNU-C5/OXTR cells compared with SNU-C5 cells, which may be related to the production of ROS in OXT-resistant cells.

Extract of Cornus officinalis Protects Keratinocytes from Particulate Matter-induced Oxidative Stress.

The skin is one of the large organs in the human body and the most exposed to outdoor contaminants such as particulate matter < 2.5 µm (PM2.5). Recently, we reported that PM2.5 induced cellular macromolecule disruption of lipids, proteins, and DNA, via reactive oxygen species, eventually causing cellular apoptosis of human keratinocytes. In this study, the ethanol extract of Cornus officinalis fruit (EECF) showed anti-oxidant effect against PM2.5-induced cellular oxidative stress. EECF protected cells against PM2.5-induced DNA damage, lipid peroxidation, and protein carbonylation. PM2.5 up-regulated intracellular and mitochondrial Ca2+ levels excessively, which led to mitochondrial depolarization and cellular apoptosis. However, EECF suppressed the PM2.5-induced excessive Ca2+ accumulation and inhibited apoptosis. The data confirmed that EECF greatly protected human HaCaT keratinocytes from PM2.5-induced oxidative stress.

Particulate Matter 2.5 Mediates Cutaneous Cellular Injury by Inducing Mitochondria-Associated Endoplasmic Reticulum Stress: Protective Effects of Ginsenoside Rb1.

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.

Niacinamide Protects Skin Cells from Oxidative Stress Induced by Particulate Matter.

Niacinamide (NIA) is a water-soluble vitamin that is widely used in the treatment of skin diseases. Moreover, NIA displays antioxidant effects and helps repair damaged DNA. Recent studies showed that particulate matter 2.5 (PM2.5) induced reactive oxygen species (ROS), causing disruption of DNA, lipids, and proteins; mitochondrial depolarization, and apoptosis of skin keratinocytes. Here, we investigated the protective effects of NIA on PM2.5-induced oxidative stress in human HaCaT keratinocytes. We found that NIA could inhibit the ROS generation induced by PM2.5, as well blocked the PM2.5-induced oxidation of molecules, such as lipids, proteins, and DNA. Furthermore, NIA alleviated PM2.5-induced accumulation of cellular Ca2+, which caused cell membrane depolarization and apoptosis, and reduced the number of apoptotic cells. Collectively, the findings show that NIA can protect keratinocytes from PM2.5-induced oxidative stress and cell damage.

Esculetin Prevents the Induction of Matrix Metalloproteinase-1 by Hydrogen Peroxide in Skin Keratinocytes.

BACKGROUND: Reactive oxygen species (ROS) are involved in various cellular diseases. Excessive ROS can cause intracellular oxidative stress, resulting in a calcium imbalance and even aging. In this study, we evaluated the protective effect of esculetin on oxidative stress-induced aging in human HaCaT keratinocytes. METHODS: Human keratinocytes were pretreated with esculetin for 30 minutes and treated with H2O2. Then, the protective effects on oxidative stress-induced matrix metalloproteinase (MMP)-1 were detected by Flou-4-AM staining, reverse transcription-PCR, Western blotting, and quantitative fluorescence assay. RESULTS: Esculetin prevented H2O2-induced aging by inhibiting MMP-1 mRNA, protein, and activity levels. In addition, esculetin decreased abnormal levels of phospho-MEK1, phospho-ERK1/2, phospho-SEK1, phospho-JNK1/2, c-Fos, and phospho-c-Jun and inhibited activator protein 1 binding activity. CONCLUSIONS: Esculetin prevented excessive levels of intracellular calcium and reduced the expression levels of aging-related proteins.

Eckol Inhibits Particulate Matter 2.5-Induced Skin Keratinocyte Damage via MAPK Signaling Pathway.

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.

Marine Compound 3-bromo-4,5-dihydroxybenzaldehyde Protects Skin Cells against Oxidative Damage via the Nrf2/HO-1 Pathway.

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 Mitigates Oxidative Damage to Human HaCaT Keratinocytes Caused by Ultraviolet B Irradiation.

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.

Luteolin promotes apoptotic cell death via upregulation of Nrf2 expression by DNA demethylase and the interaction of Nrf2 with p53 in human colon cancer cells.

Luteolin, a dietary flavone, modulates various signaling pathways involved in carcinogenesis. In this study, we investigated the molecular mechanism that underlies the apoptotic effects of luteolin mediated by DNA demethylation of the nuclear factor erythroid 2-related factor 2 (Nrf2) promoter and the interaction of Nrf2 and p53, a tumor suppressor, in human colon cancer cells. Luteolin increased the expression of apoptosis-related proteins and antioxidant enzymes. In DNA methylation, luteolin inhibited the expression of DNA methyltransferases, a transcription repressor, and increased the expression and activity of ten-eleven translocation (TET) DNA demethylases, a transcription activator. Methyl-specific polymerase chain reaction and bisulfite genomic sequencing indicated that luteolin decreased the methylation of the Nrf2 promoter region, which corresponded to the increased mRNA expression of Nrf2. In addition, luteolin increased TET1 binding to the Nrf2 promoter, as determined using a chromatin immunoprecipitation (ChIP) assay. TET1 knockdown decreased the percentages of luteolin-treated cells in sub-G1 phase and cells with fragmented nuclei. Furthermore, complex formation between p53 and Nrf2 was involved in the apoptotic effects of luteolin. These results provide insight into the mechanism that underlies the anticancer effects of luteolin on colon cancer, which involve the upregulation of Nrf2 and its interaction with the tumor suppressor.

Diphlorethohydroxycarmalol Attenuates Fine Particulate Matter-Induced Subcellular Skin Dysfunction.

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 effects. 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 5. 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.

Effect of Fermented Fish Oil on Fine Particulate Matter-Induced Skin Aging.

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.

Shikonin Exerts Cytotoxic Effects in Human Colon Cancers by Inducing Apoptotic Cell Death via the Endoplasmic Reticulum and Mitochondria-Mediated Pathways.

The apoptotic effects of shikonin (5,8-dihydroxy-2-[(1R)-1-hydroxy-4-methylpent-3-enyl]naphthalene-1,4-dione) on the human colon cancer cell line SNU-407 were investigated in this study. Shikonin showed dose-dependent cytotoxic activity against SNU-407 cells, with an estimated IC50 value of 3 µM after 48 h of treatment. Shikonin induced apoptosis, as evidenced by apoptotic body formation, sub-G1 phase cells, and DNA fragmentation. Shikonin induced apoptotic cell death by activating mitogen-activated protein kinase family members, and the apoptotic process was mediated by the activation of endoplasmic reticulum (ER) stress, leading to activation of the PERK/elF2α/CHOP apoptotic pathway, and mitochondrial Ca²âº accumulation. Shikonin increased mitochondrial membrane depolarization and altered the levels of apoptosis-related proteins, with a decrease in B cell lymphoma (Bcl)-2 and an increase in Bcl-2-associated X protein, and subsequently, increased expression of cleaved forms of caspase-9 and -3. Taken together, we suggest that these mechanisms, including MAPK signaling and the ER-and mitochondria-mediated pathways, may underlie shikonin-induced apoptosis related to its anticancer effect.

Purpurogallin Protects Keratinocytes from Damage and Apoptosis Induced by Ultraviolet B Radiation and Particulate Matter 2.5.

Purpurogallin, a natural phenol obtained from oak nutgalls, has been shown to possess antioxidant, anticancer, and anti-inflammatory effects. Recently, in addition to ultraviolet B (UVB) radiation that induces cell apoptosis via oxidative stress, particulate matter 2.5 (PM2.5) was shown to trigger excessive production of reactive oxygen species. In this study, we observed that UVB radiation and PM2.5 severely damaged human HaCaT keratinocytes, disrupting cellular DNA, lipids, and proteins and causing mitochondrial depolarization. Purpurogallin protected HaCaT cells from apoptosis induced by UVB radiation and/or PM2.5. Furthermore, purpurogallin effectively modulates the pro-apoptotic and anti-apoptotic proteins under UVB irradiation via caspase signaling pathways. Additionally, purpurogallin reduced apoptosis via MAPK signaling pathways, as demonstrated using MAPK-p38, ERK, and JNK inhibitors. These results indicate that purpurogallin possesses antioxidant effects and protects cells from damage and apoptosis induced by UVB radiation and PM2.5.