Dermatological study on dark eye circles and their treatment with newly developed cosmetics

Repeated exposure to UV radiation can induce cutaneous damage leading to permanent structural degeneration of the dermal extracellular matrix and formation of visible wrinkles. It is not so easy to efface severely UV-damaged skin, because the degenerated abnormal structure of that skin is usually fixed by tight cross-linkings. So, we think that one of the important approaches to the anti-wrinkle skin care is the treatment of photodamaged skin in the early stage. However, it is difficult for most cosmetic users to perceive their dermal UV damage. In the present study, we investigated the possibilities of two non-invasive measurements of skin mechanical properties as convenient biomarkers of degeneration of the extracellular matrix. The condition of the three-dimensional structures of dermal collagen fibres, which depends on the degree of UV damage, correlated with a mechanical parameter measured by the Resiliometer we developed. Accumulation of denatured elastic fibres (elastosis) induced by photoaging correlated with certain mechanical parameters measured by the Cutometer. These findings suggest that dermal structural changes associated with photoaging can be assessed non-invasively using these devices.     

Adaptive antioxidant response and photoaging

As the skin is always in contact with oxygen and is increasingly exposed to environmental and artificial ultraviolet (UV) irradiation the risk of photooxidative damage induced by reactive oxygen species – finally leading to phototoxicity, photoaging and skin cancer – has increased substantially. The term reactive oxygen species (ROS) includes oxygen centered radicals like the superoxide anion radical and the hydroxyl radical, but also non‐radical species such as hydrogen peroxide and singlet oxygen – all being produced in skin upon UV irradiation. In response to the attack of reactive oxygen species the skin has developed a complex antioxidant defense system including enzymatic and non‐enzymatic antioxidants. As a first line of the enzymatic antioxidative defense, superoxide dismutases reduce superoxide anion radicals to hydrogen peroxide which subsequently is detoxified to water by catalase and glutathione peroxidases. We were interested whether the antioxidant enzymes manganese superoxide dismutase (SOD2) and glutathion peroxidase (GPx1) are inducible upon UV irradiation and whether repetitive UV exposure, as practiced for the light‐hardening during phototherapy of photodermatoses, can even enhance the adaptive antioxidant response. To address this question skin fibroblasts and keratinocytes were exposed in vitro to single and repetitive UV low dose irradiation in different time intervals and afterwords challenged by high dose irradiation. The antioxidant response was measured in terms of steady state mRNA levels and activity changes of SOD2 or GPx1 as well as of the viability after challenge with high dose UV‐irradiation. Interstingly, only UVA but not UVB irradiation was able to induce the mRNA steady state levels and the activity of SOD2 in fibroblasts. However, fibroblasts incubated with the supernatants from UVB‐irradiated epidermal cells responded with an increase in SOD2. This increase on mRNA and activity levels was mediated by paracrine acting secreted factors produced by the keratinocytes. If fibroblasts were exposed repetitively to sublethal UVA doses the further up‐regulation of SOD2 correlated with the protection against high UV doses. Importantly, SOD2 basal levels of protein content and activity substantially differed within cultivated cells and skin biopsies from different individuals. These results provide evidence for an adaptive antioxidative UV response of the skin. Interindividual differences might account for differences in the susceptibility to develop photodermatologic disorders related to photosensitivity, photoaging, and skin cancer.     

Use of the synthetic superoxide dismutase/catalase mimetic EUK-134 to compensate for seasonal antioxidant deficiency by reducing pre-existing lipid peroxides at the human skin surface

The generation of reactive oxygen species (ROS) in UV-exposed skin is believed to contribute to the photoaging process. The stratum corneum (SC) contains a variety of enzymatic and non-enzymatic antioxidants to protect against various environmental sources of free radicals. We have previously shown a seasonal variation in SC catalase activity with strong deactivation in sun-exposed skin in the summer, whereas SC superoxide dismutase (SOD) activity remained intact in those conditions. This potentially leads to the local overproduction of H(2)O(2). The oxidized lipid squalene hydroperoxide accumulates at the surface of sun-exposed skin in the summer and upon exposure to ultravoilet A (UVA) doses as low as 0.1 J cm(-2) and adequate protection against excessive lipid peroxidation at times of UV exposure should be aimed for. We have been using the induction of lipid hydroperoxides at the skin surface by a single dose of UVA (1 J cm(-2)) as a model system to evaluate the protective effect of antioxidants in vivo. Topical treatment with the synthetic SOD/catalase mimetic molecule (EUK-134) 1 h before UVA exposure reduced the level of lipid peroxides at the surface of UVA-exposed skin but also baseline peroxide levels on non-irradiated skin were reduced in a dose-dependent fashion. In contrast to alpha-tocopherol, EUK-134 even reduced the level of lipid peroxides at the surface of UVA-exposed skin when it was applied after irradiation. We confirmed that this salen-manganese complex was able to reduce squalene hydroperoxide levels in vitro, suggesting peroxidase-like activity towards organic peroxides. These data support the concept that the synthetic SOD/catalase mimetic EUK-134 might be able to compensate for seasonal deficiencies in antioxidant defense capacity at the skin surface, thereby contributing to an optimal protection of the skin against the accumulation of oxidative damage.     

Molecular mechanisms of green tea polyphenols with protective effects against skin photoaging

Whereas green tea has historically been consumed in high quantities in Northeast Asia, its popularity is also increasing in many Western countries. Green tea is an abundant source of plant polyphenols exhibiting numerous effects that are potentially beneficial for human health. Accumulating evidence suggests that green tea polyphenols confer protective effects on the skin against ultraviolet (UV) irradiation-induced acceleration of skin aging, involving antimelanogenic, antiwrinkle, antioxidant, and anti-inflammatory effects as well as prevention of immunosuppression. Melanin pigmentation in the skin is a major defense mechanism against UV irradiation, but pigmentation abnormalities such as melasma, freckles, senile lentigines, and other forms of melanin hyperpigmentation can also cause serious health and aesthetic issues. Furthermore, UV irradiation initiates the degradation of fibrillar collagen and elastic fibers, promoting the process of skin aging through deep wrinkle formation and loss of tissue elasticity. UV irradiation-induced formation of free radicals also contributes to accelerated photoaging. Additionally, immunosuppression caused by UV irradiation plays an important role in photoaging and skin carcinogenesis. In this review, we summarize the current literature regarding the antimelanogenic, antiwrinkle, antioxidant, and immunosuppression preventive mechanisms of green tea polyphenols that have been demonstrated to protect against UV irradiation-stimulated skin photoaging, and gauge the quality of evidence supporting the need for clinical studies using green tea polyphenols as anti-photoaging agents in novel cosmeceuticals.     

Daily Ingestion of Aloe Vera Gel Powder Containing Aloe Sterols Prevents Skin Photoaging in OVX Hairless Mice

Estrogen deficiencies associated with menopause accelerate spontaneous skin aging and stimulate the ultraviolet (UV) irradiation‐induced photoaging of skin. However, food compositions with the potential to ameliorate the UV irradiation‐induced acceleration of skin aging with menopause have not yet been investigated in detail. In the present study, we examined the ability of plant sterols derived from Aloe vera gel to prevent the UV irradiation‐induced acceleration of skin aging in ovariectomized mice. Skin transepidermal water loss (TEWL) was significantly higher in the ovariectomy group than in the sham operation group following UVB irradiation, whereas skin elasticity was significantly lower. Ultraviolet B (UVB) irradiation induced greater reductions in skin hyaluronic acid levels and more severe collagen fiber damage in the derims in the ovariectomy group than in the sham group. The intake of AVGP significantly ameliorated this acceleration in skin aging by reducing the expression of matrix metalloproteinases (MMPs) and increasing that of epidermal growth factor (EGF) and hyaluronan synthase (HAS) in the skin. These results indicate that AVGP supplementation prevents skin damage induced by UVB irradiation and ovariectomy in part by inhibiting damage to the extracellular matrix.     

Antioxidant, anti-inflammatory and anti-browning activities of hot water extracts of oriental herbal teas

Traditionally, antioxidants are used to scavenge reactive oxygen species (ROS), which are harmful by-products of aerobic metabolism. Inulae Flos, Horsetail, Chinese Leucas, Broomweed and Indian Wikstroemia are five herbal teas commonly consumed by Asians. Our aim was to investigate the hot water extracts of these five herbal teas for their total phenolics/flavonoid contents and antioxidant capacities. Furthermore, with inflammation and hyper-pigmentation considered as two biological processes associated with elevated cellular oxidative stress, Inulae Flos water extract was chosen for further evaluation of its inhibitory effects on the production of LPS-induced inflammatory mediators (such as, TNF-α, IL-6, IL-1β) in RAW 264.7 cells and its anti-tyrosinase activity. Our findings suggest that Inulae Flos might be an alternative source as a potential antioxidant, and a noteworthy inhibitor of production of pro-inflammatory cytokines in a dose-dependent manner. Moreover, it could also serve as a potential natural food additive to prevent browning.     

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

Food Science and Biotechnology - Ultraviolet B (UVB)-induced cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-1 are representative markers for skin inflammation and photoaging,...     

鳕鱼皮胶原蛋白肽果汁饮料抗紫外线照射引起的皮肤光老化

为研究鳕鱼皮胶原蛋白肽果汁饮料(CJD)对紫外线诱导的皮肤光老化的调节作用,将ICR雄性小鼠随机分为正常组(NC)、模型组(MC)、CJD低剂量组(CJD-L)、中剂量组(CJD-M)和高剂量组(CJD-H),通过观察各组小鼠造模部位皮肤的表观特征、结合HE染色,皮肤中羟脯氨酸和水分的含量来评价CJD对小鼠皮肤光老化的防护作用;通过测定小鼠皮肤组织和血清中的总超氧化物歧化酶(T-SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)的活力,丙二醛(MDA)的含量,来探究CJD对皮肤光老化的作用途径。结果显示,与MC组相比,CJD中剂量和高剂量组可以显著抑制光老化小鼠皮肤中水分的流失(p<0.05)及胶原含量的降低(p<0.01),显著提高小鼠皮肤组织和血清中T-SOD、GSH-Px、CAT的活力(p<0.05),显著降低MDA的含量(p<0.05)。研究表明,胶原蛋白肽饮料对紫外线引起的皮肤光老化有保护作用,能够有效预防和延缓光老化。     

In vitro evaluation of the efficacy of commercial green tea extracts in UV protection

Plants with antioxidant properties are beneficial for preventing the ageing events evoked by UV light, and numerous products based on Camellila sinensis (green tea) are commercially available, many of which claiming to contain bioactive compounds that would prevent UV‐induced skin damage. In this study, we tested the efficacy of five commercial green tea extracts used to enrich cosmetic formulations for protecting human and mouse fibroblasts against UV radiation effects and compared with a fluid one prepared according to the Brazilian Pharmacopoeia recommendations. Taking into consideration that the ageing process can be accelerated by solar radiation by excessive free radical generation, leading to depletion of skin antioxidant defences, and its collapse caused by disruption of the metalloproteinase metabolism, we have used their individual (‐)‐epigallocathechin‐3‐gallate (EGCG) content, the catalase and SOD status and the matrix‐degrading metalloproteases (MMP)‐1, MMP‐9 and MMP‐13 levels as comparative parameters. The EGCG content of the commercial products showed wide variability, ranging from undetectable levels to 58.65 ± 1.12 μg mL^?1, in contrast with the fluid extract (87.82 ± 1.35 μg mL^?1). Moreover, only the pharmacopoeic extract was able to significantly reduce MMP degradation while enhancing the levels of SOD and catalase. These results indicate, for the first time, that the methodologies for preparing herbal mixtures can interfere significantly with compounds endowed with photoprotective effects, and the efficacy of products containing C. sinensis extracts thought to act against effects of solar radiation can be compromised.     

组合体外与临床测试评价植物抗氧化剂抗老化功效

基于非动物测试理念,研究植物抗氧化剂复配后的皮肤抗老化功效。方法 体外培养HaCaT角质细胞,紫外线照射诱发氧化损伤模型,分别加入白藜芦醇、原花青素和二者复配物,用MTT比色法、荧光素标记法和ELISA法检测细胞活性、活性氧簇自由基(ROS)、超氧化物岐化酶(SOD)、细胞周期及细胞凋亡的变化。对含两种植物原料的眼霜配方进行鸡胚尿囊膜血管试验(CAMVA)和牛角膜混浊渗透试验(BCOP)的组合测试评价其眼刺激性。选择平均年龄40岁的女性志愿者25名,眼部连续使用该眼霜60 d,于使用产品的第0、30和60 d分别检测皮肤的水份、水份流失、弹性和肤色等皮肤老化相关指标。结果 白藜芦醇-原花青素复配的植物抗氧化剂可明显缓解紫外线造成的HaCaT细胞氧化损伤,SOD水平明显升高(P<0.001),ROS荧光强度、细胞凋亡率及S期细胞比例均明显降低(P<0.001),细胞修复作用强于单独作用。经过替代方法组合评价其安全性后进行临床志愿者测试,证明皮肤保湿、弹性和皮肤颜色等指标得到改善。结论 白藜芦醇和原花青素两种植物抗氧化剂复配使用可有效减少皮肤氧化应激和明显改善皮肤性能。     

中波紫外线致皮肤光老化机制及茶叶抗光老化作用研究进展

过量的紫外线照射会引起皮肤的光老化,其中以中波紫外线生物学效应最为明显。皮肤的光老化会导致皮肤临床上和组织学上的多种病变,包括胶原蛋白减少、皮肤变硬、皮层变薄、色素沉积等,并会引起日光性皮炎等多种皮肤相关疾病。中波紫外线诱导皮肤光老化的原因很多,其中最重要的原因是丝裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)通路被激活,引起金属基质蛋白酶(matrix metalloproteinase,MMPs)分泌量增加导致细胞间基质被分解。茶叶作为广为人知的保健饮品,其在抗皮肤光老化方面的作用已得到了证实。茶叶水提物可以通过抑制MAPK磷酸化的途径来预防中波紫外线所致的皮肤光老化症状。文中还对该领域现有研究存在的不足进行了分析,旨在为下一步更全面深入的研究提供研究参考。     

Elastin structure and its involvement in skin photoageing

Skin aging is a complex process that may be caused by factors that are intrinsic and extrinsic to the body. Ultraviolet (UV) radiation represents one of the main sources of skin damage over the years and characterizes a process known as photoaging. Among the changes that affect cutaneous tissue with age, the loss of elastic properties caused by changes in elastin production, increased degradation and/or processing produces a substantial impact on tissue esthetics and health. The occurrence of solar elastosis is one of the main markers of cutaneous photoaging and is characterized by disorganized and non‐functional deposition of elastic fibers. The occurrence of UV radiation‐induced alternative splicing of the elastin gene, which leads to inadequate synthesis of the proteins required for the correct assembly of elastic fibers, is a potential explanation for this phenomenon. Innovative studies have been fundamental for the elucidation of rarely explored photoaging mechanisms and have enabled the identification of effective therapeutic alternatives such as cosmetic products. This review addresses cutaneous photoaging and the changes that affect elastin in this process.     

黄酮类物质对皮肤光损伤保护的研究进展

长期过量的紫外线辐射会导致一系列的皮肤疾病,包括光老化、非黑色素瘤以及黑色素瘤皮肤癌。黄酮类化合物如橙皮苷、黄芩苷、矢车菊素-3-O-葡萄糖苷、水飞蓟宾等是广泛存在于植物中的酚类物质,研究表明黄酮类化合物可以有效预防紫外线引起的各种光损伤。本文综述了黄酮类化合物通过抗炎症、氧化应激、DNA损伤以及细胞外基质的异常合成和降解来减轻紫外线引起的光损伤作用,并且讨论了它们的具体保护作用机制,为预防皮肤光损伤和开发新的黄酮类物质的保健和防晒产品提供参考。     

Role of topical and nutritional supplement to modify the oxidative stress

Background: Evidence suggests that signs of skin ageing such as wrinkling, ragging and actinic lentigines, may be connected to cumulative oxidative damage incurred throughout our lifetimes. To counteract this oxidative injury, skin is equipped with a network on enzymatic and non-enzymatic antioxidant systems, such as tocopherols, ascorbate polyphenols. All these compounds administered topically by cosmetics or by oral route by diet supplements, have been shown to exert an antioxidant/protective effect in skin or skin cells. Objective: The object of this study was to evaluate both in vitro and in vivo the activity performed by different topical antioxidants and nutritional supplements. Methods: A randomized double-blind placebo-controlled study was carried out for 8 weeks on 30 dry-skinned elderly volunteers, women aged between 48 and 59 years, with moderate xerosis and photoageing. Surface skin lipids, skin hydration and MDA determination were topically detected by 3C System. ROS was evaluated on the blood serum and on IL-3 stimulated human leukocytes by ROS Meter System at 505 nm. All the subjects applied twice a day for 2 months a nanocolloidal gel and/or take a diet supplement by oral route at the quantity of two capsules per day. All the formulations used were antioxidant-enriched (ascorbic acid, tocopherol, alpha-lipoic acid, melatonin, emblica). Results: Oxidative stress and consequently lipids peroxidation decreased from 30 to 40% (P < 0.005) in blood serum of all the subjects treated with antioxidant compounds topically and by oral route. Both free radicals recovered in blood serum and on skin (in vivo) and ROS induced by irradiation of leucocytes with UVB light (in vitro), appear sensibly lower in subjects antioxidant-treated. Conclusions: From the obtained data, it seems possible to conclude that all the compounds used play interesting role as topical and systemic photoprotectants, thanks to their interesting antioxidant property. Moreover, the antioxidant treatment seems to be a promising therapeutic approach also in reducing the oxidative stress of people affected by photoaging.     

花生四烯酸、二十二碳六烯酸和二十碳五烯酸 在炎症中的作用概述

心脑血管疾病、肿瘤、糖尿病、神经系统疾病、自身免疫等疾病严重危害着人类的生命和健康,并消耗着大量医疗资源。事实上,很多疾病发生和发展的背后都伴随着炎症反应,炎症是众多疾病的病理基础,甚至是导致这些疾病的诱因。炎症本身是机体的防御性反应,但过度的炎症反应和长期慢性炎症会损害机体的稳态。炎症的调节和控制由炎症介质介导,花生四烯酸(arachidonic acid,AA)、二十二碳六烯酸(docosahexaenoic acid,DHA)和二十碳五烯酸(eicosapentaenoic acid,EPA)等长链多不饱和脂肪酸(10ng-chain polyunsaturated fatty acids,LC-PUFAs)的衍生物是一类重要的调控炎症的介质。炎性细胞间的交流和细胞内信号传递与LC-PUFAs有关。AA经环氧酶和脂氧合酶合成的类二十烷酸主要起促炎作用,但有的也有抗炎作用。DHA和EPA在体内起抗炎作用,由它们合成的消退素(resolvins,Rvs)和保护素(protectin,PD)是重要的抗炎活性物质。DHA和EPA还可以干扰炎性细胞内信号传导途径来抑制炎症反应。本文从炎症与疾病的关系、LC-PUFAs的衍生物及其促炎和抗炎机制等方面综述了AA、DHA和EPA在炎症中的作用。     

The anti-photoaging and moisturizing effects of <Emphasis Type="Italic">Bouea macrophylla</Emphasis> extract in UVB-irradiated hairless mice

Ultraviolet (UV) light, a main cause of photoaging, leads to collapse of skin structure, resulting in wrinkle formation and dehydration. The present study assessed the anti-photoaging and moisturizing effects of Bouea macrophylla extract (BRE). UVB-irradiated hairless mice were orally administered with BME (300 mg/kg/day) for 8 weeks. BME ameliorated wrinkle formation, skin thickening, and inelasticity. BME upregulated COL1A1, COL3A1, COL4A1, and COL7A1 mRNA levels through activation of the transforming growth factor-β (TGF-β)/Smad pathway, thereby recovering the content of collagen reduced by UVB. Further, BME suppressed UVB-induced matrix metalloproteinase (MMP)-3 and MMP-13 expression and inhibited MMP-2 and MMP-9 activity by mediating the mitogen-activated protein kinases (MAPKs)/activator protein-1 (AP-1). BME improved moisture content by stimulating the expression of cornified envelope proteins and filaggrin-processing enzymes. Overall, the results show that BME prevents photoaging and promotes moisturization in UVB-irradiated hairless mice, suggesting its potential as a nutraceutical candidate for anti-photoaging and moisturizing effects.     

Preventive effect of fermented Gelidium amansii and Cirsium japonicum extract mixture against UVB-induced skin photoaging in hairless mice

Chronic ultraviolet (UV) light causes skin photoaging, characterized by fine and coarse wrinkle formation and dryness. In this study, the effect of fermented Gelidium amansii and Cirsium japonicum extract mixture (FGCM) with lactic acid bacteria on UVB-induced photoaging was evaluated in human dermal fibroblasts and SKH-1 hairless mice. In vitro, FGCM increased type I procollagen levels and suppressed UVB-induced matrix metalloproteinase-1 (MMP-1) expression more effectively than G. amansii and C. japonicum extract mixture (GCM). In vivo, oral administration of FGCM significantly inhibited UVB-induced the number and total depth of wrinkles in the dorsal skin of mice. FGCM suppressed UVB-induced epidermal thickening, and attenuated UVB-induced MMP-13 expression and MMP-2 and MMP-9 activities in dermal tissue. Furthermore, FGCM increased skin hydration and blocked transepidermal water loss in the dorsal skin of mice compared with the UVB-irradiated group. These data indicate that FGCM exerts potent anti-photoaging activities by improving wrinkle formation and dryness.     

Inhibition of skin tumor initiation,promotion, and progression by antioxidants and related compounds

Antioxidants have been shown to inhibit the induction of cancer by a wide variety of chemical carcinogens and radiation at many target sites in mice, rats, hamsters, and man. Evidence is accumulating that suggests that free radicals are important in all stages of chemical carcinogenesis. Both carcinogens and tumor promoters have also been shown to decrease the cellular activity of superoxide dismutase and catalase. A number of antioxidants and related compounds were tested to determine if they would inhibit either skin tumor initiation, promotion, or progression. In terms of skin tumor initiation, compounds such as BHT, vitamins E and C, and CuDIPS have been found to inhibit DMBA skin tumor initiation. The mechanism of action of these compounds appears to be related to their effect on the metabolism of DMBA, as BHT and CuDIPS do not inhibit the initiating activity of BP‐diol‐epoxide and MNNG. Although several antioxidants do inhibit skin tumor initiation by procarcinogens, antioxidants arc in general much more effective inhibitors of skin tumor promotion. BHT, BHA, parahydroxyanisole, disulfiran, and vitamins E and C as well as many other antioxidants are very effective inhibitors of skin tumor promotion. We also determined the effect of free radical scavengers on the progression process. Of the agents tested, glutathione and N‐acyl dehydroalamines were (he most effective in reducing carcinoma incidence. Diethyl maleate, a chemical that reduces glutathione levels, was effective in enhancing progression. In addition, overexpression of γ‐glutamyltranspeptidase (GGT), which leads to a reduction in cellular glutathione levels, also enhances progression. These results suggest that GGT has a functional role in skin tumor progression, and that a number of antioxidants are either effective inhibitors of skin tumor initiation, promotion, or progression.