• Genomics & Informatics
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• v.3 no.2
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• pp.66-72
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• 2005

The epidermis is a physiological barrier to protect organisms against environment. During the aging process, skin tissues undergo various changes including morphological and functional changes. The transcriptional regulation of genes is part of cellular reaction of aging process. In order to examine the changes of gene expression during the aging process, we used the primary cell culture system of human keratinocytes. Since UV radiation is the most important environmental skin aggressor, causing skin cancer and other problems including premature skin aging, we examined the changes of gene expression in human keratinocytes after UV irradiation using oligonucleotide microarray containing over 10,000 genes. We also compared the gene expression patterns of the senescent and UV treated cells. Expression of the variety of genes related to transcription factors, cell cycle regulation, immune response was altered in human keratinocytes. Some of down-regulated genes are represented in both senescent and UV treated cells. The results may provide a new view of gene expression following UVB exposure and aging process in human keratinocytes.

• Journal of Ginseng Research
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• v.41 no.1
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• pp.69-77
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• 2017

Background: Human skin undergoes distinct changes throughout the aging process, based on both intrinsic and extrinsic factors. In a process called photoaging, UVB irradiation leads to upregulation of matrix metalloproteinase-1, which then causes collagen degradation and premature aging. Mixtures of medicinal plants have traditionally been used as drugs in oriental medicine. Based on the previously reported antioxidant properties of Panax ginseng Meyer and Crataegus pinnatifida, we hypothesized that the mixture of P. ginseng Meyer and C. pinnatifida (GC) would have protective effects against skin aging. Methods: Anti-aging activity was examined both in human dermal fibroblasts under UVB irradiation by using Western blot analysis and in healthy human skin by examining noninvasive measurements. Results: In vitro studies showed that GC improved procollagen type I expression and diminished matrix metalloproteinase-1 secretion. Based on noninvasive measurements, skin roughness values, including total roughness (R1), maximum roughness (R2), smoothness depth and average roughness (R3), and global photodamage scores were improved by GC application. Moreover, GC ameliorated the high values of smoothness depth (R4), which means that GC reduced loss of skin moisture. Conclusion: These results suggest that GC can prevent aging by inhibiting wrinkle formation and increasing moisture in the human skin.

• Biomolecules & Therapeutics
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• v.18 no.3
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• pp.300-307
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• 2010

Photosensitized peroxidation of membrane lipids has been implicated in skin pathologies such as phototoxicity and premature aging. We have previously reported that syriacusin compounds isolated from Hibiscus Syriacus inhibited lipid peroxidation. Here, we investigated whether syriacusins could be effective inhibitor to skin aging using ultraviolet-irradiated human dermal fibroblast cells (HDFCs). Syriacusins A, B, and C inhibit the activity of human neutrophil elastase (HNE), a serine protease to degrade extracellular matrix (ECM) proteins including elastin, with $IC_{50}s$ of 8.0, 5.2, and $6.1\;{\mu}M$, respectively. No changes in cell viability were detected by syriacusins A and B in UV-B ($10\;mJ/cm^2$) irradiated HDFCs. Matrix metallo-proteinase (MMP)-1 expression in HDFCs was increased by UV-B irradiation. MMP-1 expression in UV-B irradiated HDFCs was decreased by $10\;{\mu}M$ and $20\;{\mu}M$ syriacusin A to 50% and 20% of untreated control, respectively. Syriacusin B treated with $20\;{\mu}M$ reduced MMP-1 expression in UV-B irradiated HDFCs to 60% of untreated control. Syriacusin A also inhibited MMP-2 expression accompanying the increase of type-I pro-collagen in UV-B irradiated HDFCs. These results demonstrate that syriacusin A could be a more effective compound to inhibit skin aging caused by UV irradiation. It suggests that syriacusins A and B might be developed as possible agents to treat or prevent skin aging.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.2
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• pp.105-110
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• 2017

Prolonged exposure to solar ultraviolet A (UVA) radiation has been known to cause premature skin aging (photo-aging). UVA radiation generates ROS thereby induce degenerative changes of skin such as degradation of dermal collagen, elastic fibers. Matrix metalloproteinases (MMPs), the proteolytic enzymes have been implicated as a major player in the development of UVA-induced photo-aging. Many studies have been conducted to block the harmful effects of UV radiation on the skin. Recently, we are interested in the availability of fermented red ginseng (FRG) as natural matrix metalloproteinases inhibitors (MMPIs). The efficacy difference between red ginseng and FRG has been compared. Both RG and FRG have no cytotoxic effects below the concentration of $300{\mu}g/ml$. Human dermal fibroblasts (HDFs) were pretreated with FRG or RG for 24h, followed by irradiation of UVA. Then, we measured the intracellular ROS production and the expression of MMP, $IL-1{\beta}$ at the mRNA level. We also examined the intracellular localization of $NF-{\kappa}B$ and MMP-9 on the FRG or RG treated and UVA-irradiated HDFs. FRG decreased the intracellular ROS production elicited by UVA. In addition, FRG decreased the mRNA expression of MMP-3, MMP-9, and $IL-1{\beta}$ more efficiently than RG. Furthermore, FRG suppressed the nuclear localization of $NF-{\kappa}B$, and the expression of MMP-9. Taken together, our results suggest that FRG is promising agents to prevent UVA-induced photo-aging by suppressing MMP expression and inflammation.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.11a
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• pp.79-92
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• 2007

Oxidative stress have known to be a risk factor for the degenerative processes and closely related to a lot of diseases. It is well established that antioxidants are good in protection and therapeutic means against oxidative damage. There is increasing interest in natural antioxidants and many natural antioxidants have been found and utilized as the possible protection for various diseases and skin aging. We have screened natural antioxidant agents for cosmeceuticals, nutraceuticals, and drugs as therapeutic and preventive means against oxidative stress, and have developed a number of novel antioxidants from various natural sources. A novel melanin synthesis inhibitor, Melanocin A, isolated from the metabolite of a fungal strain Eupenicillium shearii F80695 inhibited mushroom tyrosinase and melanin biosynthesis of B16 melanoma cells with $IC_{50}$ value of 9.0 nM and MIC value of $0.9\;{\mu}M$, respectively. Melanocin A also exhibited potent antioxidant activity by scavenging of DPPH and superoxide anion radicals. UV was found to increase the level of hydrogen peroxides and other reactive oxygen species (ROS) in skin tissues. This increase in ROS may not only alter the structure and function of many genes and proteins directly but may also modulate their expressions through signal transduction pathways and, ultimately, lead to skin damage. We investigated the effect of Melanocin A on UV-induced premature skin aging. Firstly, the effect of Melanocin A on UV-induced matrix metalloproteinase (MMP)-9 expression in an immortalized human keratinocyte cell line, HaCaT in vitro was investigated. Acute UV irradiation induced MMP-9 expression at both the mRNA and protein levels and Melanocin A suppressed this expression in a dose-dependent manner. We then investigated UV-induced skin changes in hairless mice in vivo by Melanocin A. Chronic exposure of hairless mouse dorsal skin to UV increased skin thickness and induced wrinkle formation and the gelatinase activities of MMP-2 and MMP-9. Moreover, Melanocin A significantly suppressed UV-induced morphologic skin changes and MMP-2 and MMP-9 expression. These results show that Melanocin A can prevent the harmful effects of UV that lead to skin aging. Therefore, we suggest that Melanocin A should be viewed as a potential therapeutic agent for preventing and/or treating premature skin aging. Terrein is a bioactive fungal metabolite isolated from Penicillium species. Terrein has a relatively simple structure and can be easily synthesized. However, the biologic effects of terrein are comparatively unknown. We found for the first time that terrein potently inhibit melanin production in melanocytes and has a strong hypopigmentary effect in a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Treatment of Mel-Ab cells with terrein (10-100 mM) for 4 days significantly reduced melanin levels in a dose-dependent manner. In addition, terrein at the same concentration also reduced tyrosinase activity. We then investigated whether terrein influences the extracellular signal-regulated protein kinase (ERK) pathway and the expression of microphthalmia-associated transcription factor (MITF), which is required for tyrosinase expression. Terrein was found to induce sustained ERK activation and MITF down-regulation, and luciferase assays showed that terrein inhibits MITF promoter activity in a dose-dependent manner. To elucidate the correlation between ERK pathway activation and a decreased MITF transcriptional level, PD98059, a specific inhibitor of the ERK pathway, was applied before terrain treatment and found to abrogate the terrein-induced MITF attenuation. Terrein also reduced the tyrosinase protein level for at least 72 h. These results suggest that terrain reduces melanin synthesis by reducing tyrosinase production via ERK activation, and that this is followed by MITF down-regulation.

• Journal of Nutrition and Health
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• v.49 no.6
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• pp.429-436
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• 2016

Purpose: Solar ultraviolet (UV) radiation causes inflammation and matrix metalloproteinase (MMP) overexpression and extracellular matrix depletion, leading to skin photoaging such as wrinkle formation, dryness, and sagging. Activation of MMP is influenced by various molecules such as reactive oxygen species (ROS), proinflammatory cytokines, and transient receptor potential vanilloid type (TRPV)-1, which are increased in UV-irradiated skin cells. Aralia elata (AE) ethanolic extract was reported to inhibit ROS generation caused by UVB-irradiation in keratinocytes. In this study, we investigated the photoprotective effect of AE ethanolic extract on UVB-irradiated human keratinocytes (HaCaT) and human dermal fibroblasts (HDF). Methods: AE was freeze-dried, extracted in 70% ethanol, and concentrated. Skin cells were treated with AE extract for 24 h and then exposed to UVB ($55mJ/cm^2$). After 48 h of incubation, proinflammatory cytokines, MMP-1, type-1 procollagen, and TRPV-1 levels were measured by ELISA or Western blotting. Results: Treatment with AE extract ($100{\mu}g/mL$) significantly inhibited UVB-induced IL-6, IL-8, and $PGE_2$ production in HaCaT by 25.6%, 5.3%, and 70.2%, respectively, and also inhibited elevation of MMP-1 and TRPV-1 caused by UVB irradiation by 20.0% and 41.9%, respectively (p < 0.05). In HDF, AE extract treatment significantly inhibited both elevation of MMP-1 and reduction of type-1 procollagen caused by UVB irradiation (p < 0.05). In addition, type-1 procollagen was elevated by AE extract treatment in normal HDFs (p < 0.05). Conclusion: AE 70% ethanol extract has photoprotective ability via reduction of proinflammatory mediators, TRPV-1 and MMP-1 production, and elevation of collagen synthesis. Our findings suggest that AE extract might be a good natural material to protect against UVB-induced premature skin aging.

• Molecules and Cells
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• v.42 no.2
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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.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.338-351
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• 2003

UV radiation is the most dangerous stress factor among permanent environmental impacts on human skin. Consequences of UV exposure are aberrant tissue architecture, alterations in skin cells including functional changes. Nowadays new kinds of outdoor leisure-time activities and changing environmental conditions make the question of sun protection more important than ever. It is necessary to recognize that self-confident consumers do not consider to change their way of life, they demand modern solutions on the basis of new scientific developments. In the past one fundamental principle of cosmetics was the use of physical and organic filter systems against damaging UV-rays. Today new research results demonstrate that natural protecting cell mechanisms can be activated. Suitable biological actives strongly support the protection function not from the surface but from the inside of the cell. A soy seed preparation (SSP) was proven to stimulate natural skin protective functions. The major functions are an increased energy level and the prevention of DNA damage. These functions can I be defined as biological UV protection. The tumor suppressor protein p53 plays a key role in the regulation of DNA repair. p53 must be transferred into the phosphorylated form to work as transcription factor for genes which are regulating the cell cycle or organizing DNA repair. A pretreatment with SSP increases the phosphorylation rate of p53 of chronically UV-irradiated human keratinocytes significantly. According to the same test procedure SSP induces a dramatic increase in the expression of the tumor suppressor protein p14$^{ARF}$ that is supporting the p53 activity by blocking the antagonist of p53, the oncoprotein Mdm2. Mdm2, a ubiquitin E3-ligase, downregulates p53 and at the same time it prevents phosphorylation of p53. The positive influence of the tumor suppressor proteins explains the stimulation of DNA repair and prevention of sunburn cell formation by SSP, which was proven in cell culture experiments. In vivo the increased skin tolerance against UV irradiation by SSP could be confirmed too. We have assumed, that an increased repair potential provides full cell functionality.y.

• Journal of Life Science
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• v.29 no.12
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• pp.1321-1328
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• 2019

Intermediate-wavelength solar radiation, also known as ultraviolet B (UVB: 290-320 nm) radiation, may cause premature aging and oxidative damage-dependent skin cancer in humans. UVB-induced formation of reactive oxygen species (ROS)-often a consequence of excessive exposure to these rays-could activate matrix metalloproteinases (MMPs) such as MMP-1 and MMP-3. These enzymes break down type I collagen in human fibroblasts. In this study, we assessed the antioxidant and anti-aging effects of ethyl acetate extract of blueberry (EEB). An antioxidant test in blueberries evaluated ROS production using CCD-986sk cells and DPPH assay. In order to evaluate the anti-wrinkle efficacy of blueberries, the MMP-1 production and type 1 procollagen synthesis evaluated and the expression of MMP 1, 3 were tested through Western blot and RT- PCR. EEB exhibited 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and reduced the production of UVB-induced ROS. Also, EEB inhibited UVB-induced processes associated with photoaging and skin cancer, such as reduction in procollagen production and increase in MMP-1 production. More precisely, EEB (50 ㎍/ml) markedly suppressed mRNA and protein levels of MMP-1 and -3. The anti-aging effects are attributable to the antioxidant activity of EEB. These findings indicate that EEB has a protective effect against UVB-induced aging in human fibroblast cells by regulating the levels of type-1 procollagen, MMP-1, and MMP-3.

• Journal of People, Plants, and Environment
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• v.23 no.2
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• pp.191-199
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• 2020

Noni has been used for medicinal purposes for more than 2,000 years in South Pacific Polynesia, China and India, and has been heavily ingested as an extract for its excellent antioxidant and anti-inflammatory effects. However, a recent study found that the noni extract causes digestive disorders, kidney problems, and liver diseases, which made it necessary to use it for other purposes than as an extract. In this study, we want to evaluate the potential of noni as an anti-oxidant, anti-inflammatory and anti-wrinkling agent. Methods: Noni was freeze-dried, extracted in water, and concentrated. Skin cells were treated with the noni extract for 24 hrs and then were exposed to UVB (55 mJ/cm²). After 48 hrs of incubation, pro-inflammatory cytokine, elastase, MMP-1 and type-1 procollagen levels were measured by ELISA. Results: To find out the antioxidant effect of the noni extract, the DPPH and ABTS radical scavenging activity experiments were conducted and the noni extract showed 97.0 % and 92.0 % antioxidant efficacy at 200 ㎍/mL respectively. The noni extract (50 and 100 ㎍/mL) decreased IL-6 and TNF-α in RAW 264.7 cells induced by LPS in a concentration-dependent manner. In the RT-PCR experiment involving NO production, the noni extract (50 and 100 ㎍/mL) inhibited NO production by strongly inhibiting iNOS mRNA expression, and also inhibited the elevation of MMP-1 and elastases caused by UVB irradiation by 25.0 % and 7.0 % respectively. In addition, type-1 procollagen was elevated by 20.0 % by the noni extract treatment in HaCaT cells. Conclusion: The noni extract has photoprotective ability by reducing proinflammatory mediators, elastase and MMP-1 production, and elevation of collagen synthesis. Our findings suggest that the noni extract might be a good natural substance to protect against UVB-induced premature skin aging.