• Biomolecules & Therapeutics
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• 제13권3호
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• pp.150-155
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• 2005

The ethanolic extract of chestnut (Castanea crenata S. et Z., Fagaceae) inner shell (CISE) and one of its components, ellagic acid (EA), were evaluated for their protective effects against 1, 1-diphenyl-2-picryl hydrazine (DPPH) free radical generation and hydrogen peroxide-induced oxidative DNA damage in a mammalian cell line. CISE and EA were shown to possess the free radical scavenging effect against DPPH radical generation, significantly. They were also found to strongly inhibit hydrogen peroxide-induced DNA damage from Chinese hamster lung (CHL) cell, assessed by single cell gel electrophoresis assay and 8-hydroxy -2'-deoxy guanosine (8-OH-2'dG) assay. Furthermore, topical application of CISE [$12.5\%$(w/w) cream] and ellagic acid [$1.0\%$(w/w) cream] for 14 days potently inhibited malondialdehyde (MDA) formation of mouse dorsal skin (a marker of lipid peroxidation) induced by ultraviolet B exposure. Therefore, CISE and its component, ellagic acid, may be the useful natural antioxidants by scavenging free radicals, inhibition of lipid peroxidation and protecting oxidative DNA damage when topically applied.

• Biomolecules & Therapeutics
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• 제32권1호
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• pp.84-93
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• 2024

Rosmarinic acid (RA) is a phenolic ester that protects human keratinocytes against oxidative damage induced by ultraviolet B (UVB) exposure, however, the mechanisms underlying its effects remain unclear. This study aimed to elucidate the cell signaling mechanisms that regulate the antioxidant activity of RA and confirm its cyto-protective role. To explore the signaling mechanisms, we used the human keratinocyte cell line HaCaT and SKH1 hairless mouse skin. RA enhanced glutamate-cysteine ligase catalytic subunit (GCLC) and glutathione synthetase (GSS) expression in HaCaT cells in a dose- and time-dependent manner. Moreover, RA induced nuclear factor erythroid-2-related factor 2 (NRF2) nuclear translocation and activated the signaling kinases protein kinase B (AKT) and extracellular signal-regulated kinase (ERK). Treatment with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the ERK inhibitor U0126, and small interfering RNA (siRNA) gene silencing suppressed RA-enhanced GCLC, GSS, and NRF2 expression, respectively. Cell viability tests showed that RA significantly prevented UVB-induced cell viability decrease, whereas the glutathione (GSH) inhibitors buthionine sulfoximine, LY294002, and U0126 significantly reduced this effect. Moreover, RA protected against DNA damage and protein carbonylation, lipid peroxidation, and apoptosis caused by UVB-induced oxidative stress in a concentration-dependent manner in SKH1 hairless mouse skin tissues. These results suggest that RA protects against UVB-induced oxidative damage by activating AKT and ERK signaling to regulate NRF2 signaling and enhance GSH biosynthesis. Thus, RA treatment may be a promising approach to protect the skin from UVB-induced oxidative damage.

• Molecules and Cells
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• 제42권2호
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• pp.151-160
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• 2019

Ultraviolet (UV) radiation of the sunlight, especially UVA and UVB, is the primary environmental cause of skin damage, including topical inflammation, premature skin aging, and skin cancer. Previous reports show that activation of nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) in human skin fibroblasts and keratinocytes after UV exposure induces the expression and release of proinflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), and subsequently leads to the production of matrix metalloproteases (MMPs) and growth factor basic fibroblast growth factor (bFGF). Here, we demonstrated that TNFR2-SKEE and TNFR2-SKE, oligopeptides from TNF receptor-associated factor 2 (TRAF2)-binding site of TNF receptor 2 (TNFR2), strongly inhibited the interaction of TNFR1 as well as TNFR2 with TRAF2. In particular, TNFR2-SKE suppressed UVB- or $TNF-{\alpha}$-induced nuclear translocalization of activated $NF-{\kappa}B$ in mouse fibroblasts. It decreased the expression of bFGF, MMPs, and COX2, which were upregulated by $TNF-{\alpha}$, and increased procollagen production, which was reduced by $TNF-{\alpha}$. Furthermore, TNFR2-SKE inhibited the UVB-induced proliferation of keratinocytes and melanocytes in the mouse skin and the infiltration of immune cells into inflamed tissues. These results suggest that TNFR2-SKE may possess the clinical potency to alleviate UV-induced photoaging in human skin.

• Biomolecules & Therapeutics
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• 제24권1호
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• pp.75-84
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• 2016

This study was designed to investigate the cytoprotective effect of rosmarinic acid (RA) on ultraviolet B (UVB)-induced oxidative stress in HaCaT keratinocytes. RA exerted a significant cytoprotective effect by scavenging intracellular ROS induced by UVB. RA also attenuated UVB-induced oxidative macromolecular damage, including protein carbonyl content, DNA strand breaks, and the level of 8-isoprostane. Furthermore, RA increased the expression and activity of superoxide dismutase, catalase, heme oxygenase-1, and their transcription factor Nrf2, which are decreased by UVB radiation. Collectively, these data indicate that RA can provide substantial cytoprotection against the adverse effects of UVB radiation by modulating cellular antioxidant systems, and has potential to be developed as a medical agent for ROS-induced skin diseases.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.557-563
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• 2015

Skin aging is the most readily observable process involved in human aging. Ultraviolet B (UVB) radiation causes photo-oxidation via generation of reactive oxygen species (ROS), thereby damaging the nucleus and cytoplasm of skin cells and ultimately leading to cell death. Recent studies have shown that high levels of solar UVB irradiation induce the synthesis of matrix metalloproteinases (MMPs) in skin fibroblasts, causing photo-aging and tumor progression. The MMP family is involved in the breakdown of extracellular matrix in normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as arthritis and metastasis. We investigated the effect of diphlorethohydroxycarmalol (DPHC) against damage induced by UVB radiation in human skin keratinocytes. In UVB-irradiated cells, DPHC significantly reduced expression of MMP mRNA and protein, as well as activation of MMPs. Furthermore, DPHC reduced phosphorylation of ERK and JNK, which act upstream of c-Fos and c-Jun, respectively; consequently, DPHC inhibited the expression of c-Fos and c-Jun, which are key components of activator protein-1 (AP-1, up-regulator of MMPs). Additionally, DPHC abolished the DNA-binding activity of AP-1, and thereby prevented AP-1-mediated transcriptional activation. These data demonstrate that by inactivating ERK and JNK, DPHC inhibits induction of MMPs triggered by UVB radiation.

• 동의생리병리학회지
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• 제27권2호
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• pp.183-188
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• 2013

Ultraviolet (UV) B irradiation induces the production of matrix metalloproteinases (MMPs), which are responsible for the degradation or synthesis inhibition of collagenous extracellular matrix in connective tissues, causing skin photoaging. In this study, we examined the inhibitory effect of MMP-1 expression of yam extract in tumor necrosis factor-alpha (TNF-${\alpha}$)-stimulated human dermal fibroblast neonatal (HDFn) cell and preventive effect of UVB-induced damage in hairless mice skin. The synthesis of procollagen and the release of MMP-1 in HDFn cells were measured by EIA kit and MMP-1 assay kit, respectively. UVB radiation was applied to the backs of the mice three times a week for 8 weeks. Mice were randomly divided into three groups, and were topical application with the Dioscorea batatas (DB, 6%) or vehicle. Reduction of TNF-${\alpha}$-induced procollagen synthesis was increased by DB (50 ug/ml), which was higher than positive control group (TGF-${\beta}$). Also, pre-treatment of HDFn cells with DB inhibited TNF-${\alpha}$-induced release of MMP-1. In vivo study, we found that preventive effect of DB against UV-induced epidermal thickness. DB suppressed the expression of MMP-3 and MMP-13 induced by UVB irradiation. Our results show that DB have preventive effect of UV-induced skin damage in hairless mice.

• 한방안이비인후피부과학회지
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• 제21권1호
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• pp.70-82
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• 2008

Objective : The purpose of this study is to examine the effects of Baickbujasan(BB) on the skin damage and depigmentation. Method : The inhibition of tyrosinase activity, melanogenesis and cell viability in cultured B16 melanoma cells were measured. In order to test effects of reduction of melanogenesis, B16 F-10 mouse melanoma stem line was employed to extract melanin from cultured cell, where BB was added or not, and was dissolved in alkali for colorimetric analysis. Also, in order to test skin alteration in C57BL/6 after UV irradiation, the animals were grouped into a UV urradiation group and UV irradiation after BB application group. Dopa oxidase tissue staining was excuted to invesitage the change in the distribution of active melanin cell. The distribution of active melanin cell in inner skin of iNOS after damage from UVB irradiation and the manifestation condition of P53 which takes part in natural death of keratinocyte were examined. Result : The results indicate that BB has significant effects on tyrosinase activity, and melanogenesis in vivo test. BB seems to reduce C57BL/6, external dermatological damage, for instance, erythematous papule, eczema, loss of keratinocyte, reduction in pus, and relieves dermatological damages. Conclusion : BB can be applied externally for UV protection and depigmentation.

• 대한본초학회지
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• 제31권4호
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• pp.87-91
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• 2016

Objectives : In order to confirm whether extracts of different parts of Zostera marina (ZM), a marine flowering plant, can be used as cosmetic ingredients, this study evaluated their cytotoxicity and cytoprotective effects against ultraviolet B (UVB). Inflammatory responses induced by UV stimuli are also associated with the aging of the skin.Methods : We investigated the effects of ZM extracts on cells through the water soluble tetrazolium salt-1(WST-1) assay for cell viability. In order to investigate the anti-inflammatory effects, we evaluated the suppression of Cyclooxygenase-2 (COX-2) expression by ZM extracts in HaCaT cells with UVB-induced damages, and also evaluated the production of Prostaglandin E₂ (PGE₂) in RAW 264.7 cells with LPS-induced damages.Results : High cell viabilities above 90% were observed in all types of ZM extracts, except for whole ZM extract at 0.5 mg/ml; in keratinocytes with UVB-induced damages, the cell viabilities were above 80% when treated with all types of ZM extracts. We confirmed their anti-inflammatory effects by investigating the suppression of inflammatory mediators. In keratinocytes with UVB-induced damages, COX-2 expression decreased in the experimental group treated with ZM extract. Similarly, in RAW 264.7 cells where inflammation was induced with LPS, the biosynthesis of PGE₂ was inhibited.Conclusion : These results suggest that ethanol extracts from Zostera marina may have value as the potential anti-inflammatory medicinal plant. Also based on the abovementioned results, ZM extract protects skin cells from UV-induced damages, and thus can be used in topically applied products for skin protection.

• 대한본초학회지
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• 제32권5호
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• pp.13-18
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• 2017

Objectives : The aim of this study is to investigate anti-inflammation of Leonurus sibiricus methanol extract against UVB-damage in fibroblast. The skin is continuously exposed to damage from environmental stresses. UV radiation causes a variety of biological effects especially on the skin, including inflammation and photoaging. Methods : In this study, we tried to search for Leonurus sibiricus which exhibit protective activities against UVB-induced cytotoxicity and oxidative cell death, NO and $PGE_2$ production. HS68 cells were exposed to UVB ($120mJ/cm^2$) and treated with various concentrations (0, 0.25, 0.5, 1, 2, 4, $8mg/m{\ell}$) of Leonurus sibiricus methanol extract for additional 24 h. Intracellular reactive oxygen species (ROS) levels generated by UV radiation were detected using a spectrofluorometer after DCF-DA staining. Also, HS68 cells were irradiated with UVB and then treated with Leonurus sibiricus methanol extract for 12 h. The lipid peroxidation was assayed by measuring the levels of 8-isoprostane secreted into the culture medium. Results : UVB-induced cytotoxicity and cell death were effectively suppressed by treatment of Leonurus sibiricus aqueous methanol extracts. Oxidative cell damage was mediated $PGE_2$ in UVB-induced HS68 fibroblast cell, which was significantly inhibited by treatment with Leonurus sibiricus extracts. Also, the protective effect of these extract seemed to be mediated by inhibited intracellular ROS generation and lipid peroxidation in dose-dependent manner. Conclusion : These results suggest that Leonurus sibiricus aqueous methanol extracts may have anti-aging effects new functional materials against oxidative UVB stress-mediated skin damages.

• Biomolecules & Therapeutics
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• 제21권6호
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• pp.470-475
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• 2013

Ultraviolet (UV) radiation is a major environmental factor that leads to acute and chronic reactions in the human skin. UV exposure induces wrinkle formation, DNA damage, and generation of reactive oxygen species (ROS). Most mechanistic studies of skin physiology and pharmacology related with UV-irradiated skin have focused on proteins and their related gene expression or single-targeted small molecules. The present study identified and analyzed the alteration of skin metabolites following UVB irradiation and topical retinyl palmitate (RP, 5%) treatment in hairless mice using direct analysis in real time (DART) time-of-flight mass spectrometry (TOF-MS) with multivariate analysis. Under the negative ion mode, the DART ion source successfully ionized various fatty acids including palmitoleic and linolenic acid. From DART-TOF-MS fingerprints measured in positive mode, the prominent dehydrated ion peak (m/z: 369, M+H-$H_2O$) of cholesterol was characterized in all three groups. In positive mode, the discrimination among three groups was much clearer than that in negative mode by using multivariate analysis of orthogonal partial-least squares-discriminant analysis (OPLS-DA). DART-TOF-MS can ionize various small organic molecules in living tissues and is an efficient alternative analytical tool for acquiring full chemical fingerprints from living tissues without requiring sample preparation. DART-MS measurement of skin tissue with multivariate analysis proved to be a powerful method to discriminate between experimental groups and to find biomarkers for various experiment models in skin dermatological research.