UVB-induced Skin Damage Research Articles

Protective effect of pre- and post-vitamin C treatments on UVB-irradiation-induced skin damage

Several studies have reported the effects of vitamin C (L-ascorbic acid, AA) on ultraviolet B (UVB)-induced cell damage using cultured keratinocytes. However, the epidermis consists of multiple cell layers, and the effect of AA on UVB-induced damage to the human epidermis remains unclear. Therefore, we investigated the effect of AA on UVB-induced skin damage using reconstituted human epidermis. The reconstituted human epidermal surface was treated with 100 and 500 mM AA and cultured for 3 h before (pre-AA treatment) or after (post-AA treatment) 120 mJ/cm2 UVB irradiation. Pre- and post-AA treatments of the epidermal surface suppressed UVB-induced cell death, apoptosis, DNA damage, reactive oxygen species (ROS) production, and the inflammatory response by downregulating tumour necrosis factor-α (TNF-α) expression and release. Moreover, the pre-AA treatment was more effective at preventing UVB-induced skin damage than the post-AA treatment. In summary, pre- and post-AA treatments of the epidermis prevent UVB-induced damage.

Protection against UVB-Induced Wrinkle Formation in SKH-1 Hairless Mice: Efficacy of Tricin Isolated from Enzyme-Treated Zizania latifolia Extract.

Tricin, a flavone found mainly in rice bran and sugarcane, has various beneficial effects. It has proven to be a clinically safe and selective potent inhibitor of different cancer cell lines. In this study, we evaluated the efficacy of enzyme-treated Zizania latifolia (ETZL) and its major active compound tricin on skin photoaging in SKH-1 hairless mice. Tricin (0.3 mg/kg) and ETZL (50, 150, and 300 mg/kg) were orally administrated to mice for 14 weeks; no cytotoxicity was observed during the entire experimental period. After UVB exposure, we observed significant increases in keratinization, coarse wrinkles, loss of moisture, thickened epidermis, and collagen fiber degradation in the dorsal skin. These features of photoaging were significantly suppressed after oral administration of tricin or ETZL. In addition, the protein expression of collagen effectively increased in ETZL (150 and 300 mg/kg)-treated mice, while the increased metalloproteinase (MMP)-1 and MMP-3 expressions were reduced after exposure to tricin or ETZL, although the effects were not dose-dependent. These data indicate that ETZL may be effective for attenuation of UVB-induced skin damage and photoaging in hairless mice, possibly by inhibiting MMPs expression.

Apigenin Inhibits UVB-Induced Skin Carcinogenesis: The Role of Thrombospondin-1 as an Anti-Inflammatory Factor

We have previously demonstrated that apigenin promotes the expression of antiangiogenic protein thrombospondin-1 (TSP1) via a mechanism driven by mRNA-binding protein HuR. Here, we generated a novel mouse model with whole-body THBS-1 gene knockout on SKH-1 genetic background, which allows studies of UVB-induced acute skin damage and carcinogenesis and tests TSP1 involvement in apigenin's anticancer effects. Apigenin significantly inhibited UVB-induced carcinogenesis in the wild-type (WT) animals but not in TSP1 KO (TKO) mice, suggesting that TSP1 is a critical component of apigenin's chemopreventive function in UVB-induced skin cancer. Importantly, TKO mice presented with the elevated cutaneous inflammation at baseline, which was manifested by increased inflammatory infiltrates (neutrophils and macrophages) and elevated levels of the two key inflammatory cytokines, IL-6 and IL-12. In agreement, maintaining normal TSP1 expression in the UVB-irradiated skin of WT mice using topical apigenin application caused a marked decrease of circulating inflammatory cytokines. Finally, TKO mice showed an altered population dynamics of the bone marrow myeloid progenitor cells (CD11b+), with dramatic expansion of the population of neutrophil progenitors (Ly6ClowLy6Ghigh) compared to the WT control. Our results indicate that the cutaneous tumor suppressor TSP1 is a critical mediator of the in vivo anticancer effect of apigenin in skin, specifically of its anti-inflammatory action.

Cbl-b deficiency provides protection against UVB-induced skin damage by modulating inflammatory gene signature

Exposure of skin to ultraviolet (UV) radiation induces DNA damage, inflammation, and immune suppression that ultimately lead to skin cancer. However, some of the pathways that regulate these events are poorly understood. We exposed mice to UVB to study its early effects in the absence of Cbl-b, a known suppressor of antitumor immune response in the skin. Cbl-b−/− mice were protected from UV-induced cell damage as shown by the lower number of cyclobutane pyrimidine dimers and sunburn cells in exposed skin compared to wild-type mice. Microarray data revealed that deficiency of Cbl-b resulted in differential expression of genes involved in apoptosis evasion, tumor suppression and cell survival in UV-exposed skin. After UVB, Cbl-b−/− mice upregulated gene expression pattern associated with regulation of epidermal cell proliferation linked to Wnt signaling mediators and enzymes that relate to cell removal and tissue remodeling like MMP12. Additionally, the skin of Cbl-b−/− mice was protected from chronic inflammatory responses and epidermal hyperplasia in a 4-weeks UVB treatment protocol. Overall, our results suggest a novel role for Cbl-b in regulating inflammation and physiologic clearance of damaged cells in response to UVB by modulating inflammatory gene signature.

Chemistry and Pharmacology of Artocarpin: An Isoprenyl Flavone from Artocarpus Species

Artocarpin is an isoprenyl flavone from Artocarpus species (Moraceae). Trees of the genus comprise about 50 species, and are native to tropical and subtropical Asia. First isolated from the root of A. heterophyllus (jackfruit), artocarpin has been reported in other Artocarpus species such as A. altilis, A. chempeden, A. kemando and A. maingayi. Recently, artocarpin has also been isolated from A. incisus, A. chama, A. lowii, A. anisophyllus, A. scortechinii, A. odoratissimus and A. hirsutus. It has a molecular formula of C26H28O6 and a 5,7,2’,4’-tetrahydroxylated structure with three benzene rings. Ring B has a 2’,4’-resorcinol moiety and there is a methoxy group at C-7 of ring A. At C-3 and C-6 of artocarpin are the isoprenyl substituents. Some data on the content of artocarpin in extracts and fractions of different solvents and species of Artocarpus have been presented. Other flavones prenylated at C-3 and C-6 include artelasticin, artelastofuran, cudraflavone C and norartocarpin. The inhibition of tyrosinase and melanogenesis are two skin-whitening activities of artocarpin. It protects UVB-induced skin damage. Besides its cosmeceutical activities of skin-whitening and photo protection, artocarpin possesses other pharmacological properties such as cytotoxic, anti-inflammatory, antioxidant, antimicrobial, antiandrogen, antitubercular, antiplasmodial, neuraminidase inhibitory, termiticidal and wound healing activities. In the conclusion, some research studies of interest for the future have been proposed.

Ginsenoside C-Mx Isolated from Notoginseng Stem-leaf Ginsenosides Attenuates Ultraviolet B-mediated Photoaging in Human Dermal Fibroblasts.

Notoginseng is a traditional herbal medicine widely used for medicinal therapy in Asia, as it contains numerous ginsenosides with pharmacological effects. In this study, we submitted Notoginseng stem-leaf (NGL) ginsenosides to an enzyme to create a reaction with the monomer products of ginsenoside C-Mx and then investigated the ability of ginsenoside C-Mx to protect the skin against ultraviolet B-induced injury in normal human dermal fibroblasts (NHDFs). Ginsenoside C-Mx alleviated UVB-induced intracellular reactive oxygen species (ROS), MMP-1 and IL-6 expression while accelerating TGF-β and procollagen type I secretion. In addition, ginsenoside C-Mx reversed UVB-induced procollagen type I reduction by regulating the TGF-β/Smad signaling pathway. Moreover, ginsenoside C-Mx inhibited activation of AP-1 transcription factor, an inducer of MMPs. Ginsenoside C-Mx displayed an outstanding antioxidant capacity, increasing expression of cytoprotective antioxidants such as HO-1 and NQO-1 expression by enhancing the nuclear accumulation of Nrf2. Interestingly, application of ginsenoside C-Mx treatment (1, 10, 20μm) significantly diminished UVB-induced suppressed NF-κB expression, decreasing the over-released inflammatory cytokines. Taken together, our findings indicated that ginsenoside C-Mx may act as a promising natural cosmetic ingredient for prevention and treatment of UVB-induced skin damage.

Mackerel-derived fermented fish oil protects skin against UVB-induced cellular damage by inhibiting oxidative stress

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.

1136 Galectin-3 regulates UVB-induced inflammation in skin

Galectin-3, a β-galactoside binding lectin, can be detected in diverse types of cells, including epidermal keratinocytes. Regulatory roles of galectin-3 in the pathogenesis of various malignant and inflammatory skin disorders have been reported, but the known roles of galectin-3 in UVB-induced inflammation in skin are still limited and the underlying molecular mechanisms remain elusive. In this study, we aimed to evaluate the regulatory roles of galectin-3 in UVB-induced inflammatory responses in skin by using primary normal human epidermal keratinocytes (NHEKs) and galectin-3 knockout mice as the models. Our results demonstrated knockdown of galectin-3 in NHEKs attenuated the UVB-induced production of active IL-. UVB-induced ASC cross-linking and active caspase-1 formation were reduced but LDH release was not affected after galectin-3 knockdown. In addition, after galectin-3 knockdown, UVB-induced IL-8, TNF-α and COX-2 expression in NHEKs were also down-regulated. Furthermore, UVB-induced production of reactive oxygen species in NHEKs was also reduced after galectin-3 knockdown. In the animal study, UVB-induced skin inflammation and damage were less severe in galectin-3 knockout mice than in wild type mice grossly and histologically. When measuring the physiological parameters, UVB-induced transepidermal water loss and skin erythema index were also reduced in galectin-3 knockout mice compared with wild type mice. In conclusion, current findings indicate that galectin-3 plays a crucial regulatory role in UVB-induced inflammation, suggesting a potential way to prevent UVB-induced skin damage by targeting galectin-3 in skin.

Antioxidative Effect of Quetiapine on Acute Ultraviolet-B-Induced Skin and HaCaT Cell Damage

Quetiapine is a new type of antipsychotic drug, with effective protection of pheochromocytoma PC12 cells from oxidative stress-induced apoptosis. Ultraviolet-B radiation can increase reactive oxygen species (ROS) production, resulting in significant inflammatory responses in damaged skin. Thus, the purpose of this study is to explore whether quetiapine protects the skin from intermediate-wave ultraviolet (UVB)-induced damage through antioxidant stress. In vivo, we found quetiapine treatment was able to significantly decrease skin thickness, erythema, and edema, as well as inflammation compared to control group. Moreover, quetiapine treatment increased the activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In addition, it reduced the production of malondialdehyde (MDA), a kind of oxidized lipid. In vitro, we found that quetiapine blocked UVB-induced intracellular ROS generation and maintained the cell activity at a normal level. Furthermore, we tested the phosphorylation of p38 both in vivo and in vitro, and we found that quetiapine could inhibit phosphorylation of p38, which is caused by UVB irradiation. We concluded that quetiapine was able to relieve UVB-induced skin damage through its antioxidative properties. These effects might be associated with p38 MAPK signaling pathway.

Preventive effect of Ephedra sinica extract on UVB-induced COX-2 and MMP-1 expression.

Ultraviolet B (UVB)-induced cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-1 are representative markers for skin inflammation and photoaging, respectively. To evaluate compounds that may counteract the effects of UVB-induced skin damage, we developed an immortalized human keratinocyte (HaCaT) cell line with an MMP-1 reporter construct. Among the 30 botanical extracts screened, we selected Ephedra sinica extract (ESE) as a promising candidate and confirmed that ESE significantly suppresses UVB-induced COX-2 and MMP-1 expression in HaCaT cells. Treatment with ESE also potently suppressed UVB-induced ERK1/2 phosphorylation, as well as UVB-induced MEK1/2 and Raf phosphorylation in HaCaT cells. These findings suggest that our MMP-1 reporter system can be used to evaluate compounds with anti-inflammatory and anti-photoaging effects. We also report that ESE has potent suppressive effects against COX-2 and MMP-1 expression, which occurs via downregulation of Raf/MEK1/2/ERK1/2 phosphorylation.

Isocitrate dehydrogenase 2 deficiency exacerbates dermis damage by ultraviolet-B via ΔNp63 downregulation

Isocitrate dehydrogenase 2 (IDH2) is a key enzyme that maintains the balance of mitochondrial redox status by generating NADPH as a reducing factor, which is used to reduce oxidized antioxidant proteins and oxidized glutathione. Therefore, the role of IDH2 is crucial in organs that are easily influenced by reactive oxygen species (ROS) or mechanical damage. Humans are constantly exposed to ultraviolet (UV) radiation throughout their lifetime, which can cause various cutaneous diseases, such skin carcinoma, dermatitis, and sunburn. ROS play an important role in the initial step of these diseases; therefore, IDH2 deficient mice (Idh2−/−) could be a useful model to investigate UV-mediated skin damage. When we exposed the dorsal skin of Idh2−/− mice to UVB, pyrimidine dimers and (6-4) photoproducts (6-4PPs), marker of photoproducts generated by UVB, were found in the dermis of the knockout mice. Increased collagen degradation, apoptosis, inflammation, and ROS levels in the dermis were also observed. These results indicated that UVB could reach the dermis by penetrating the epidermis. We then attempted to determine how the epidermis was breached, and observed a decrease in the expression level of ΔNp63, a major protein required for epidermis generation, in the Idh2−/− mice. The mito-TEMPO supplement significantly ameliorates UVB-induced damage in the skin of Idh2−/− mice. In the present study, we provided a role for IDH2 in protection against UVB-induced skin damage and a new connection between IDH2 and ΔNp63.

Photochemoprotective effect of a fraction of a partially purified extract of Byrsonima crassifolia leaves against UVB-induced oxidative stress in fibroblasts and hairless mice

Ultraviolet B (UVB) irradiation increases the risk of various skin disorders, leading to inflammation and oxidative stress and thereby increasing the risk of skin photoaging and carcinogenesis. The use of photochemoprotectors such as natural products with antioxidant and anti-inflammatory properties represents a strategy for preventing UVB-induced skin damage. We investigated the photochemoprotective effect of a fraction of a partially purified extract of Byrsonima crassifolia leaves (BCF) on fibroblasts and hairless mice exposed to UVB radiation. The mixture of phenolic compounds in BCF prevented the decrease in reduced glutathione (GSH) levels in fibroblast cultures induced by UVB radiation more than some of their individual standards ((+)-catechin (CAT), epigallocatechin gallate and quercetin 3-O-β-d-glucopyranoside). Prepared gel formulations increased skin antioxidant activity, and BCF components and the CAT standard were retained in the HRS/J hairless mice epidermis 2h after application. Topical treatment with the BCF or CAT formulations (1%) significantly reduced the decrease in GSH levels and decreased myeloperoxidase activity and the secretion of pro-inflammatory cytokines IL-1β and IL-6 induced by UVB radiation (P<0.05), indicating that both BCF and CAT had anti-inflammatory effects. BCF inhibited UVB-induced metalloproteinase (MMP)-9 secretion/activity, whereas CAT had no effect on MMP-9 activity in the skin of treated animals. These results therefore suggest that BCF can be used as a photochemoprotective agent and antioxidant in the prevention/treatment of inflammation and oxidative stress of the skin induced by UVB radiation.

Protective effects of compounds from Garcinia mangostana L. (mangosteen) against UVB damage in HaCaT cells and hairless mice.

UltravioletB (UVB) radiation causes alterations in the skin, such as epidermal thickening, wrinkle formation and inflammation. Therefore, preventing UVB-induced skin damage can promote general health among the human population. Garcinia mangostana L. (mangosteen) is a fruit that has become a popular botanical dietary supplement because of its perceived role in promoting overall health. The present study investigated the photoprotective effects of α-, β-, γ-mangostins and gartanin against UVB radiation using the HaCaT immortalized human keratinocyte cell line as an invitro model and hairless mice as an invivo model. UVB radiation increased the expression of matrix metalloproteinase(MMP)‑1 and ‑9 and decreased the mRNA expression levels of involucrin, filaggrin and loricrin in HaCaT cells; however, these changes were attenuated by pretreating the cells with α-, β-, γ-mangostins and gartanin. Among these compounds, α-mangostin exhibited the greatest effects in reducing UVB-induced skin wrinkles, inhibited epidermal thickening in hairless mice invivo. Exposure to UVB radiation increased the expression of MMPs and pro-inflammatory cytokines and activated mitogen-activated protein kinases in hairless mice, but these changes were attenuated by α-mangostin. The authors suggested that α-mangostin exerts anti-wrinkle and anti-aging properties.

Fisetin Regulates Nrf2 Expression and the Inflammation-Related Signaling Pathway to Prevent UVB-Induced Skin Damage in Hairless Mice.

Chronic ultraviolet (UV) exposure may cause skin damage, disrupt skin barrier function, and promote wrinkle formation. UV induces oxidative stress and inflammation, which results in extracellular matrix degradation in the dermis and epidermal hyperplasia. Our previous study demonstrated that fisetin exerts photoprotective activity by inhibiting mitogen-activated protein kinase/activator protein-1/matrix metalloproteinases (MMPs) activation. In this study, fisetin was applied topically to investigate its antiphotodamage effects in hairless mice. The erythema index (a* values) and transepidermal water loss were evaluated to assess skin damage, and immunohistochemical staining was conducted to elucidate the photoprotective mechanism of fisetin. The results revealed that the topical application of fisetin reduced UVB-induced increase in the a* value and wrinkle formation. In addition, fisetin inhibited epidermal hyperplasia and increased the collagen content in the dermis. Fisetin exerted photoprotective activity by inhibiting the expression of MMP-1, MMP-2, and cyclooxygenase-2 and increasing the expression of nuclear factor erythroid 2-related factor. Furthermore, fisetin increased the expression of filaggrin to prevent UVB-induced barrier function disruption. Altogether, the present results provide evidence of the effects and mechanisms of fisetin’s antiphotodamage and antiphotoinflammation activities.

Ameliorative effects of Diospyros lotus leaf extract against UVB-induced skin damage in BALB/c mice

The aim of this study was to investigate the protective effect of Diospyros lotus leaf extract (DLE) on UVB-induced skin damage in mice. UVB irradiation of mice skin incurred significant damage to mice skin; increased thiobarbituric acid-reactive substance level; decreased superoxide dismutase; and glutathione levels in mice skin tissues. More so, UVB irradiation led to collagen degradation and infiltration of mast cell and neutrophils into mice skin leading to inflammation. However, topical application of DLE significantly reversed these conditions with the result comparable to l-ascorbic acid. Myricitrin, gallic acid, astragalin, myricetin-3-O-glactosside, and myricetin through high-performance liquid chromatography analysis were further determined to be the primary active compounds in DLE. In conclusion, our study showed that DLE has potentials as local therapeutic materials against skin damage by inhibiting oxidative stress and UVB-induced skin damage.

Potential effect of compounds isolated from Coffea arabica against UV-B induced skin damage by protecting fibroblast cells

Ultraviolet (UV) radiation has adverse effects on extracellular matrix (ECM) proteins, leading to formation of wrinkles a hallmark of premature skin aging. The adverse effects of UV radiation are associated with induction of matrix metalloproteinases (MMPs) expression and degradation of collagen and elastin. The present study investigated anti-wrinkle effects of chlorogenic acid (CGA), pyrocatechol (PC) and 3,4,5-tricaffeoyl quinic acid (TCQ), isolated from beans of Coffea arabica, against UV-B stimulated mouse fibroblast cells (CCRF) by measuring expression levels of MMP-1, 3, 9, and type-I procollagen. The three compounds were isolated and purified from coffee grounds using column chromatography and structural examination was evaluated by nuclear magnetic resonance (NMR) analysis. Among the three isolated compounds, CGA effectively suppressed the expression of the MMP-1, 3, and 9 and increased synthesis of type-I procollagen as compared UV-B-stimulated CCRF cells. In addition, CGA dose-dependently inhibited intracellular reactive oxygen species (ROS) production in CCRF cells stimulated by UV radiation. Moreover, CGA displayed a good sun protection factor (SPF) and in vitro DNA damage protection together with inhibition of enzyme xanthine oxidase. The enzyme inhibitory kinetic behavior of CGA was determined by Lineweaver-Burk plot, displayed a mixed type enzyme inhibition with 260.3±4.5μM, Ki value. The results indicate that CGA has potential to be used as a preventive agent against premature skin aging induced by UV radiation.

Byrsonima crassifolia extract and fraction prevent UVB-induced oxidative stress in keratinocytes culture and increase antioxidant activity on skin

Solar ultraviolet radiation exposure, particularly UVB rays (280–320nm), can lead to skin lesions, photocarcinogenesis and acceleration of skin photoaging since UVB radiation may reach both the epidermal and dermal layers of the skin. Treatments that can ameliorate UVB-induced skin damage include natural extracts, which can act as skin photochemoprotective agents. Byrsonima crassifolia is widely used in the folk medicine. Previously studies have shown high antioxidant activity of BC leaves extracts. In this study we described the first photochemoprotective potential of Byrsonima crassifolia extract (BCP) and fraction (BCF) against UVB-induced damage in keratinocytes and the ability of topical formulations with BCP or BCF to increase the antioxidant activity in pig ear skin. The results of characterization of BCP and BCF indicate that the phenolic content was increased two-fold after an enrichment process for obtaining BCF. Despite differences in the phenolic content, both BCP and BCF exhibited similar IC50 values for lipid peroxidation and the DPPH method during the antioxidant activity study. However, for the chemiluminescence assay using the xanthine/luminol/XOD, BCF exhibited higher antioxidant activity than BCP. The different phenolic content in BCP and BCF did not influence their photochemoprotective activity in HaCaT cells, and both samples exhibited similar levels of protection. After treatment with BCP and BCF (1.2–5μg/mL) and UVB irradiation exposure, the effect of lipid peroxidation in vitro was maintained in cell culture, and both IL-6 and TNF-α secretion and NF-κB activation were suppressed. After the development of the different formulations, BCP and BCF increased the antioxidant activity on skin and the formulation containing BCF showed higher skin retention, especially for (+) catechin, which was able to pass through the stratum corneum. Based on these findings, BCF could be topically applied to prevent/treat the damage induced by UVB radiation in the skin.

Mirabilis Jalapa L. Protein as Inductor of Apoptosis on UVB-induced Skin Damage in Mice

Background: Mirabilis jalapa L. protein (MJ-Protein) has been shown to have antioxidant and anti-inflammatory effects in vitro. Thus, it has a potential protective effect against ultraviolet B (UVB)-induced skin damage.Objective: To determine the protective effect and mechanism of MJ protein in UVB-radiation exposed mouse skin.Methods: In this experimentalstudy, 30 female BALB/c mice aged 6 weeks were exposed to a single dose of UVB irradiation with 3 minimal erythema doses (MEDs) and continued with the treatment of 0.6 mg MJ-Protein topically. The number of apoptotic body (sunburn cells) formed in epidermal layers of mouse dorsal skin was assessed at 1, 24, 48, 72, 96 and 120h after UVB irradiation was compared to that of the control group. The difference in the sunburn cells number between two groups were analyzed using independent T-test with the level of significance of 0.05. The apoptosis mechanism was confirmed qualitatively by caspase-3 and DNA fragmentation analysis in vitro.Results:At 24 h after the UVB exposure (peak time for sunburn cells formation), there was a significant increase in the sunburn cells number in the group treated with topical application of MJ-Protein. There was increased caspase-3 expression and DNA fragmentation in HeLa cells treated with MJ-Protein.Conclusions: MJ-Protein protects againts UVB-induced skin damage in mice trough apoptosis induction.Bangladesh Journal of Medical Science Vol.16(3) 2017 p.423-427

Linalool prevents oxidative stress activated protein kinases in single UVB-exposed human skin cells.

Ultraviolet-B radiation (285–320 nm) elicits a number of cellular signaling elements. We investigated the preventive effect of linalool, a natural monoterpene, against UVB-induced oxidative imbalance, activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling in HDFa cells. We observed that linalool treatment (30 μM) prevented acute UVB-irradiation (20 mJ/cm2) mediated loss of activities of antioxidant enzymes in HDFa cells. The comet assay results illustrate that linalool significantly prevents UVB-mediated 8-deoxy guanosine formation (oxidative DNA damage) rather than UVB-induced cyclobutane pyrimidine (CPD) formation. This might be due to its ability to prevent UVB-induced ROS formation and to restore the oxidative imbalance of cells. This has been reflected in UVB-induced overexpression of MAPK and NF-κB signaling. We observed that linalool inhibited UVB-induced phosphorylation of ERK1, JNK and p38 proteins of MAPK family. Linalool inhibited UVB-induced activation of NF-κB/p65 by activating IκBa. We further observed that UVB-induced expression of TNF-α, IL6, IL-10, MMP-2 and MMP-9 was modulated by linalool treatment in HDFa cells. Thus, linalool protects the human skin cells from the oxidative damages of UVB radiation and modulates MAPK and NF-κB signaling in HDFa cells. The present findings substantiate that linalool may act as a photoprotective agent against UVB-induced skin damages.

Protective Role of Mitochondrial Peroxiredoxin III against UVB-Induced Apoptosis of Epidermal Keratinocytes

UVB light induces generation of reactive oxygen species, ultimately leading to skin cell damage. Mitochondria are a major source of reactive oxygen species in UVB-irradiated skin cells, with increased levels of mitochondrial reactive oxygen species having been implicated in keratinocyte apoptosis. Peroxiredoxin III (PrxIII) is the most abundant and potent H2O2-removing enzyme in the mitochondria of most cell types. Here, the protective role of PrxIII against UVB-induced apoptosis of epidermal keratinocytes was investigated. Mitochondrial H2O2 levels were differentiated from other types of ROS using mitochondria-specific fluorescent H2O2 indicators. Upon UVB irradiation, PrxIII-knockdown HaCaT human keratinocytes and PrxIII-deficient (PrxIII-/-) mouse primary keratinocytes exhibited enhanced accumulation of mitochondrial H2O2 compared with PrxIII-expressing controls. Keratinocytes lacking PrxIII were subsequently sensitized to apoptosis through mitochondrial membrane potential loss, cardiolipin oxidation, cytochrome c release, and caspase activation. Increased UVB-induced epidermal tissue damage in PrxIII-/- mice was attributable to increased caspase-dependent keratinocyte apoptosis. Our findings show that mitochondrial H2O2 is a key mediator in UVB-induced apoptosis of keratinocytes and that PrxIII plays a critical role in protecting epidermal keratinocytes against UVB-induced apoptosis through eliminating mitochondrial H2O2. These findings support the concept that reinforcing mitochondrial PrxIII defenses may help prevent UVB-induced skin damage such as inflammation, sunburn, and photoaging.