ArticleLiterature Review

Skin photoprotection by natural polyphenols: Anti-inflammatory, antioxidant and DNA repair mechanisms

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Abstract

Epidemiological, clinical and laboratory studies have implicated solar ultraviolet (UV) radiation in various skin diseases including, premature aging of the skin and melanoma and non-melanoma skin cancers. Chronic UV radiation exposure-induced skin diseases or skin disorders are caused by the excessive induction of inflammation, oxidative stress and DNA damage, etc. The use of chemopreventive agents, such as plant polyphenols, to inhibit these events in UV-exposed skin is gaining attention. Chemoprevention refers to the use of agents that can inhibit, reverse or retard the process of these harmful events in the UV-exposed skin. A wide variety of polyphenols or phytochemicals, most of which are dietary supplements, have been reported to possess substantial skin photoprotective effects. This review article summarizes the photoprotective effects of some selected polyphenols, such as green tea polyphenols, grape seed proanthocyanidins, resveratrol, silymarin and genistein, on UV-induced skin inflammation, oxidative stress and DNA damage, etc., with a focus on mechanisms underlying the photoprotective effects of these polyphenols. The laboratory studies conducted in animal models suggest that these polyphenols have the ability to protect the skin from the adverse effects of UV radiation, including the risk of skin cancers. It is suggested that polyphenols may favorably supplement sunscreens protection, and may be useful for skin diseases associated with solar UV radiation-induced inflammation, oxidative stress and DNA damage.

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... Skin cells are constantly exposed to the harmful effects of free radicals that are generated by both endogenous and exogenous factors [15]. Although the skin has natural defence mechanisms against free radicals, it is susceptible to their effects when they are produced in excessive amounts [11,16]. ROS affect the epidermis and dermis. ...
... Plants can exhibit a variety of properties, both medicinal in the case of certain skin diseases and promoting skin health, including through antioxidant effects [24,28]. The free-radical scavenging ability and antioxidant properties of plants are associated with the presence of components such as polyphenols, tocopherols, carotenoids, ascorbic acid, and macromolecules (including polysaccharides and peptides), as well as components of essential oils [16,24,31]. ...
... Phenolic acids hydroxybenzoic acid derivatives (e.g., p-hydroxybenzoic, vanillic acid, protocatechuic acid) predominantly radical scavenging via hydrogen atom donation; also electron donation and singlet oxygen quenching -exhibit depigmenting properties by controlling the activity of tyrosinase -moisturize the skin and stimulate the synthesis of collagen and elastin fibres -anti-allergic, anti-cancer, anti-inflammatory, antimicrobial, anti-ageing properties -act as photoprotectors, prevent UV-induced erythema formation in the skin hydroxycinnamic acid derivatives (e.g., caffeic, p-coumaric, ferulic acids) Tannins hydrolysable tannins inhibition of lipid peroxidation and lipoxygenases in vitro, ability to scavenge radicals (e.g., hydroxyl, superoxide, and peroxyl) -promote tropoelastin synthesis and reduce elastase activity -protect the skin from inflammation caused by external irritation -anti-inflammatory and wound healing properties -antimicrobial, cytotoxic, anti-cancer, antiulcer activity The diversity of polyphenol structures is linked to their multi-faceted biological activity. Polyphenolic compounds, in addition to their anti-inflammatory, moisturizing, smoothing, soothing, anti-ageing, UV-protective, antibacterial, and capillary stabilizing properties, exert a strong antioxidant effect [16,23,35,43,44]. The antioxidant activity of phenolic compounds, resulting from various mechanisms of action, consists of (1) eliminating reactive oxygen species through direct reaction with free radicals, scavenging of free radicals, and enhancing dismutation of free radicals to compounds with much lower reactivity; (2) inhibiting or potentiating the action of numerous enzymes, e.g., oxidases, and increasing the expression of antioxidant proteins such as CAT and SOD; (3) chelating prooxidative metal ions (e.g., iron or copper); and 4) enhancing the effect of other antioxidants (e.g., restoring the original form of tocopherols from the radical form or prolonging the action of ascorbic acid) [42,45]. ...
Article
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Natural substances have traditionally been used in skin care for centuries. There is now an ongoing search for new natural bioactives that not only promote skin health but also protect the skin against various harmful factors, including ultraviolet radiation and free radicals. Free radicals, by disrupting defence and restoration mechanisms, significantly contribute to skin damage and accelerate ageing. Natural compounds present in plants exhibit antioxidant properties and the ability to scavenge free radicals. The increased interest in plant chemistry is linked to the growing interest in plant materials as natural antioxidants. This review focuses on aromatic and medicinal plants as a source of antioxidant substances, such as polyphenols, tocopherols, carotenoids, ascorbic acid, and macromolecules (including polysaccharides and peptides) as well as components of essential oils, and their role in skin health and the ageing process.
... UV-B (290-320 nm) and UV-A (320-400 nm) are able to pass through earth's ozone layer and have significant effects on the epidermis layer of the skin [2,3]. The UV radiation generates free radicals which can lead to skin aging, skin damage, and in some cases, skin cancer [4]. The main method for preventing the free radicals' activity and skin damage is by blocking UV radiation. ...
... Many natural polyphenol extracts have been tested as UV blockers. However, most of them are small molecules with low purity, have poor photo-stability [4], and cannot block the full UV spectrum [5]. Therefore, more stable natural macromolecular sunscreens are needed. ...
... The antitumor activity of flavonoids, in general, has been extensively described and documented thus far. 74,80,[123][124][125][126][127][128] Therefore, we present in detail our findings on the modulation of oncogenic skin cancer pathways by luteolin and its derivatives. Luteolin, a natural flavonoid commonly found in many plant raw materials, exhibits multiple biological effects, including anti-inflammatory, antioxidant, antiallergic, and anticancer properties. ...
... ,[78][79][80] Additionally, the SHH signaling pathway, consisting of transmembrane proteins Ptch1, Smo, and Shh, is important for sporadic and hereditary BCC. However, it is not associated with SCC. ...
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Cutaneous malignant melanoma is the fastest growing and the most aggressive form of skin cancer that is diagnosed. However, its incidence is relatively scarce compared to the highest mortality rate of all skin cancers. The much more common skin cancers include nonmelanoma malignant skin cancers. Moreover, over the past several decades, the frequency of all skin cancers has increased much more dynamically than that of almost any other type of cancer. Among the available therapeutic options for skin cancers, chemotherapy used immediately after the surgical intervention has been an essential element. Unfortunately, the main problem with conventional chemopreventive regimens involves the lack of response to treatment and the associated side effects. Hence, there is a need for much more effective anticancer drugs. Correspondingly, the targeted alternatives have involved phytochemicals, which are safer chemotherapeutic agents and exhibit competitive anticancer activity with high therapeutic efficacy. Among polyphenolic compounds, some flavonoids and their derivatives, which are mostly found in medicinal plants, have been demonstrated to influence the modulation of signalling pathways at each stage of the carcinogenesis process, which is also important in the context of skin cancers. Hence, this review focuses on an exhaustive overview of the therapeutic effects of luteolin and its derivatives in the treatment and prevention of skin cancers. The bioavailability and structure-activity relationships of luteolin derivatives are also discussed. This review is the first such complete account of all of the scientific reports concerning this particular group of natural compounds that target a specific area of neoplastic diseases.
... This indicates that even though D. edulis bark contain high amount of phenolics, flavonoids and tannins [25] , these compounds might not be available in the form that effect the required properties in the active creams. Bioavailability and metabolism of polyphenols may influence their effectiveness [47] . In case of topical delivery of polyphenols, the penetration of polyphenols into the skin is limited; successful delivery of plant polyphenols requires cream-based, organic solventbased or lipid soluble topical formulations that can enhance the penetration of the polyphenols [47] . ...
... Bioavailability and metabolism of polyphenols may influence their effectiveness [47] . In case of topical delivery of polyphenols, the penetration of polyphenols into the skin is limited; successful delivery of plant polyphenols requires cream-based, organic solventbased or lipid soluble topical formulations that can enhance the penetration of the polyphenols [47] . Studies had shown that complex Phyllanthus emblica extract-phospholipid cream revealed higher localisation of gallic acid in the skin as compared to conventional P. emblica extract cream [48] . ...
Article
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Modern skincare products are formulated using plant extracts as active ingredients. Leaf and stem of Talinum triangulare and leaf and bark of Dacryodes edulis extracts were used for the development of cosmetic formulations for in vivo evaluation of their moisturizing effects. Absence of redness, itching, or blemishes on the forearms of volunteers, with the cream without the extracts (control) and with creams containing the extracts (actives), confirmed the safety of these formulations. The pH of the active creams and control (4.9-5.4) were within the pH of the skin. There were no coalescence of dispersed phase, phase separation and change in colours of the active creams and the control from their respective initial colours stored at 7 °C, 30 °C and 40 °C for 90 days. Creams prepared with ethanol extracts of T. triangulare leaf hydrated the skin more than the other plant materials, indicating its potentials as moisturising ingredient to treat dry skin.
... Curcumin (CUR) is a plant polyphenol isolated from the rhizome of Curcuma longa Linn. Its free radicals scavenging, lipid peroxidation, and oxidative cell injury inhibiting properties are found to be beneficial in a variety of dermatological disorders such as dermatitis, acne, psoriasis, eczema, etc. (Nichols and Katiyar, 2010). CUR inhibits tyrosinase synthesis which is the primary enzyme responsible for a-melanocyte stimulating hormone (MSH) binding on melanocortin 1 receptor (MC1R) that impede adenylate cyclase conversion into cyclic adenosine monophosphate (cAMP), an essential step in melanin synthesis (Park et al. 2011). ...
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The main aim of the present study was to develop curcumin (CUR) loaded permeation enhancer-lipid vesicles for the treatment of hyperpigmentation. Hyperpigmentation is an acquired skin disorder characterized by uneven skin coloration, mainly in the regions of the facial skin, affecting millions of people worldwide. It often occurs in visible areas, hence causing significant negative psychological and social impacts. In the present study, curcumin-loaded permeation enhancer nanovesicles (PE-NVs) were developed by modified ethanol injection method and dimethyl sulfoxide was added as a penetration enhancer. PE-NVs were subjected to various physicochemical characterizations and drug permeation studies across the skin. The PE-NVs were tested for their efficacy in a sunlight-induced hyperpigmented rabbit skin model. Topical application of PE-NVs reduced symptoms of hyperpigmentation as compared with CUR methanolic solution because of higher accumulation because of better permeation into skin layers. Histopathological studies also confirmed the effectiveness of PE-NVs, since they reduced hyperpigmentation-induced lesions. Results confirmed that PE-NVs is a potential drug delivery system for topical administration drugs to treat skin-associated inflammatory disorders.
... Ultraviolet (UV) radiation is an important exogenous factor in the pathogenesis of human skin and can lead to the development of a series of skin disorders, including sunburn (erythema and edema), hyperplasia, carcinogenesis, DNA damage, immunosuppression, and photoaging [4][5][6][7][8]. Scientists categorize UV light into three different subtypes, according to wavelength: UV-A (λ = 320-400 nm) is UV light with the longest wavelength, and the least harmful, UV-B (λ = 290-320 nm), is mostly absorbed (95%) by the ozone in Earth's Persimmon (Diospyros kaki Thunb.) ...
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Persimmon (Diospyros kaki Thunb.) fruits are a remarkable source of carotenoids, which have shown protective effects against UV radiation in bacteria, fungi, algae, and plants. The aim of this study was to analyze the photoprotection provided by an acetone extract, rich in carotenoids and obtained from byproducts derived from the persimmon juice industry, against UV-induced cell death in the keratinocyte HaCaT cell line. For this purpose, the cytotoxicity and phototoxicity of carotenoid extract, as well as its intracellular reactive oxygen species (ROS) scavenging and anti-adhesive activities towards HaCaT cells, were evaluated. The in vitro permeation test provided information about the permeability of the carotenoid extract. Persimmon extracts, rich in carotenoids (PEC), were absorbed by HaCaT keratinocyte cells, which reduced the UV-induced intracellular ROS production in treated cells. Thus, PEC exerted a photoprotective and regenerative effect on UV-irradiated HaCaT cells, and this protection was UV dose-dependent. No cytotoxic effect was observed in HaCaT cultures at the concentration tested. PEC treatment also stimulated the adhesion capacity of skin microbiome to HaCaT cells, while exhibiting a significant anti-adhesive activity against all tested pathogens. In conclusion, PEC showed potential for use as a functional ingredient in skin-care products.
... Theaflavins, which are found in black tea, have been shown to inhibit UVB-induced AP-1 induction by suppressing the action of extracellular-regulated kinase (ERK) and c-jun N-terminal kinase (JNK). Tea polyphenols can also prevent UVB-induced phosphatidyl-inositol 3kinase activation (IP3K) [169,170]. On a molecular level, oral green tea administration to SKH-1 mice increased the number of UV-induced p53-and p21-positive cells, as well as the number of apoptotic sunburn cells [171]. In addition to reducing the amount of ROS in the skin, tea polyphenols provide photoprotection by counteracting UVB-induced local and systemic immunosuppression. ...
Article
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In recent years, interest in the health effects of natural antioxidants has increased due to their safety and applicability in cosmetic formulation. Nevertheless, efficacy of natural antioxidants in vivo is less documented than their prooxidant properties in vivo. Plant extracts rich in vitamins, flavonoids, and phenolic compounds can induce oxidative damage by reacting with various biomolecules while also providing antioxidant properties. Because the biological activities of natural antioxidants differ, their effectiveness for slowing the aging process remains unclear. This review article focuses on the use of natural antioxidants in skincare and the possible mechanisms underlying their desired effect, along with recent applications in skincare formulation and their limitations.
... The skin health-promoting effects of PCs include photoprotection, anti-inflammatory, antiaging and photo-chemoprevention [41]. The presence of these properties is due to the structure of the PCs. ...
Article
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Human skin works as a barrier against the adverse effects of environmental agents, including ultraviolet radiation (UVR). Exposure to UVR is associated with a variety of harmful effects on the skin, and it is one of the most common health concerns. Solar UVR constitutes the major etiological factor in the development of cutaneous malignancy. However, more than 90% of skin cancer cases could be avoided with appropriate preventive measures such as regular sunscreen use. Plants, constantly irradiated by sunlight, are able to synthesize specialized molecules to fight against UVR damage. Phenolic compounds, alkaloids and carotenoids constitute the major plant secondary metabolism compounds with relevant UVR protection activities. Hence, plants are an important source of molecules used to avoid UVR damage, reduce photoaging and prevent skin cancers and related illnesses. Due to its significance, we reviewed the main plant secondary metabolites related to UVR protection and its reported mechanisms. In addition, we summarized the research in Mexican plants related to UV protection. We presented the most studied Mexican plants and the photoprotective molecules found in them. Additionally, we analyzed the studies conducted to elucidate the mechanism of photoprotection of those molecules and their potential use as ingredients in sunscreen formulas.
... With the improvement of living level of people, the attention to skin health is also increasing. It has become a trend to use natural plant extracts to protect skin against oxidative aging (Nichols and Katiyar, 2010). Paeonia extracts have been widely used in skin care, and the main organs used were roots and flowers, and the main functional components were monoterpene glycosides and tannins (Adki and Kulkarni, 2020;Kim et al., 2020;Letsiou et al., 2020;Qiu et al., 2016). ...
Article
Paeonia is famous as ornamental, medicinal plant, and edible oil crop in China. The seeds of peonies are rich in unsaturated fatty acids, monoterpene glycosides, sterols and stilbenes which have antioxidant and anti-inflammatory effects, etc. In this study, the composition and content of stilbenes in the seed coat extracts (SCE) from 50 populations of 18 species and two subspecies of Paeonia were determined by high performance liquid chromatography - diode array detection (HPLC-DAD). The results showed that the composition and content of stilbenes, especially suffruticosol B and gnetin H, differed significantly between Paeonia species, while there were small differences between populations of the same species. All the samples were clustered into two groups according to the stilbenes in SCE. The difference between the two groups was mainly reflected in the content of suffruticosol B and gnetin H. Furthermore, all samples showed high antioxidant activity, which was significantly positively correlated with the total polyphenol content. The SCE of P. anomala and P. lactiflora at different concentrations could effectively inhibit the production of matrix metalloproteinase − 1 (MMP-1) in keratinocytes, and then achieve the effect of inhibiting cell aging. This study provided a valuable reference for the value-added utilization of Paeonia seed coat.
... Furthermore, recent studies using latitude (31) and altitude as substitutes for sunlight exposure indicated that decreased latitude (32) or increased altitude (33) (substituting for elevated sunlight exposure) was related to a reduced risk of obesity. However, excess exposure to ultraviolet radiation could overwhelm the cutaneous antioxidant capacity, leading to inflammation and oxidative stress (8,34). Therefore, sunshine duration exceeding the appropriate range may associate with an elevated risk of obesity, which is consistent with our results. ...
Article
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Background Accumulated researches revealed that both fine particulate matter (PM 2.5 ) and sunlight exposure may be a risk factor for obesity, while researches regarding the potential effect modification by sunlight exposure on the relationship between PM 2.5 and obesity are limited. We aim to investigate whether the effect of PM 2.5 on obesity is affected by sunlight exposure among the general population in China. Methods A sample of 47,204 adults in China was included. Obesity and abdominal obesity were assessed based on body mass index, waist circumference and waist-to-hip ratio, respectively. The five-year exposure to PM 2.5 and sunlight were accessed using the multi-source satellite products and a geochemical transport model. The relationship between PM 2.5 , sunshine duration, and the obesity or abdominal obesity risk was evaluated using the general additive model. Results The proportion of obesity and abdominal obesity was 12.6% and 26.8%, respectively. Levels of long-term PM 2.5 ranged from 13.2 to 72.1 μg/m ³ with the mean of 46.6 μg/m ³ . Each 10 μg/m ³ rise in PM 2.5 was related to a higher obesity risk [OR 1.12 (95% CI 1.09-1.14)] and abdominal obesity [OR 1.10 (95% CI 1.07-1.13)]. The association between PM 2.5 and obesity varied according to sunshine duration, with the highest ORs of 1.56 (95% CI 1.28-1.91) for obesity and 1.66 (95% CI 1.34-2.07) for abdominal obesity in the bottom quartile of sunlight exposure (3.21-5.34 hours/day). Conclusion Long-term PM 2.5 effect on obesity risk among the general Chinese population are influenced by sunlight exposure. More attention might be paid to reduce the adverse impacts of exposure to air pollution under short sunshine duration conditions.
... Antioxidants are able to minimize and prevent damage from free-radical reactions because of their potential to contribute electrons that neutralize the radical production [46][47][48]. Many plants produce secondary metabolites, such as flavonoids and polyphenols, that serve as antioxidants and play a crucial role in a variety of biological processes [49][50][51]. Plants and natural products are, thus, a significant source of antioxidants, which may eliminate free radical damage and protect the organism from the harmful effects of excessive oxidative stress. As a result of our research, we found that methanolic extracts had varying levels of antioxidant activity. ...
Article
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Efficient methods for callus induction and the high-frequency plant regeneration of Ruta chalepensis L. were established, and the phytochemical potential and antioxidant activity of a donor plant, ex-vitro-established micropropagated plants, and callus were also studied. Yellowish-green callus was induced with a frequency of 97.8% from internode shoot segments of the donor plant growing in soil in the botanical garden cultured on Murashige and Skoog (MS) medium containing 10 μM 2,4-D (2,4-dichlorophenoxyacetic acid) and 1 μM BA (6-benzyladenine). Adventitious shoots were regenerated from the yellowish-green callus on MS medium containing 5.0 μM (BA) and 1.0 μM 1-naphthaleneacetic acid (NAA), with a regeneration frequency of 98.4% and a maximum of 54.6 shoots with an average length of 4.5 cm after 8 weeks. The regenerated shoots were rooted in a medium containing 1.0 μM IBA (indole-3-butyric acid) and successfully transferred to ex vitro conditions in pots containing normal garden soil, with a 95% survival rate. The amounts of alkaloids, phenolics, flavonoids, tannins, and antioxidant activity of the ex-vitro-established micropropagated plants were higher than in the donor plant and callus. The highest contents of hesperidin and rutin (93.3 and 55.9 µg/mg, respectively) were found in the ex-vitro-established micropropagated plants compared to those obtained from the donor plant (91.4 and 31.0 µg/mg, respectively) and callus (59.1 and 21.6 µg/mg, respectively). The genetic uniformity of the ex-vitro-established micropropagated plants was appraised by the ISSR markers and compared with the donor plant. This is the first report describing the callus-mediated plant regeneration, as well as the production of phenolic compounds and antioxidant activities in R. chalepensis, which might be a potential alternative technique for the mass propagation and synthesis of bioactive compounds such as hesperidin and rutin.
... Due to their potential to contribute electrons that may neutralize radical production, antioxidants are useful in lowering and preventing further damage through free-radical responses [20][21][22][23]. Several plants generally manufacture secondary metabolites such as polyphenols and flavonoids that function as antioxidants and play essential roles in a variety of biological processes [24][25][26][27][28][29][30]. A primary source of antioxidants that scavenge free radicals and fight against unwanted health problems caused by oxidative stress may thus be plants as well as natural ingredients. ...
Article
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The use of F. religiosa might be beneficial in inflammatory illnesses and can be used for a variety of health conditions. In this article, we studied the identification of antioxidants using (DPPH) 2, 2-Diphenyl-1-picrylhydrazylradical scavenging activity in Ficus religiosa, as F. religiosa is an important herbal plant, and every part of it has various medicinal properties such as antibacterial properties that can be used by the researchers in the development and design of various new drugs. The 2, 2-Diphenyl-1- picrylhydrazyl (DPPH) is a popular, quick, easy, and affordable approach for the measurement of antioxidant properties that includes the use of the free radicals used for assessing the potential of substances to serve as hydrogen providers or free-radical scavengers (FRS). The technique of DPPH testing is associated with the elimination of DPPH, which would be a stabilized free radical. The free-radical DPPH interacts with an odd electron to yield a strong absorbance at 517 nm, i.e., a purple hue. An FRS antioxidant, for example, reacts to DPPH to form DPPHH, which has a lower absorbance than DPPH because of the lower amount of hydrogen. It is radical in comparison to the DPPH-H form, because it causes decolorization, or a yellow hue, as the number of electrons absorbed increases. Decolorization affects the lowering capacity significantly. As soon as the DPPH solutions are combined with the hydrogen atom source, the lower state of diphenylpicrylhydrazine is formed, shedding its violet color. To explain the processes behind the DPPH tests, as well as their applicability to Ficus religiosa (F. religiosa) in the manufacture of metal oxide nanoparticles, in particular MgO, and their influence on antioxidants, a specimen from the test was chosen for further study. According to our findings, F. religiosa has antioxidant qualities and may be useful in the treatment of disorders caused by free radicals.
... 4,5 UVA, which makes up the majority of UV radiation that reaches the earth's surface, penetrates into the dermis and can cause oxidative damage and photoaging. 6 UVA may also indirectly cause DNA damage through the generation of reactive oxygen species (ROS) that oxidize guanine bases in DNA, leading to mutagenesis. 4 Compared with UV radiation, the impact of visible light (VL) on human skin has received relatively little attention. ...
Article
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The effects of solar radiation on human skin differ based on skin phototype, the presence or absence of photodermatoses, biological capacity to repair DNA damage, wavelength, intensity of sun exposure, geographic latitude, and other factors, underscoring the need for a more tailored approach to photoprotection. To date, the focus of photoprotection guidelines has been to prevent sunburn and DNA damage induced by ultraviolet (UV) radiation, both UVB and UVA; however, several recent studies have shown that visible light (VL) also generates reactive oxygen and nitrogen species that can contribute to skin damage and pigmentation on the skin, particularly in people of color. Therefore, dark-skinned individuals, while naturally better protected against UVB radiation by virtue of high eumelanin content in melanocytes, may need additional protection from VL-induced skin damage. The current options for photoprotection products need to expand, and potential strategies against VL include the addition of iron oxide, titanium dioxide, and biologically relevant antioxidants to sunscreen formulations, as well as supplementation with orally active antioxidants.
... Photoaging is the result of chronic UV radiation exposure from the sun [6]. UV rays can be divided in UVC, UVB, and UVA, according to the wavelengths of radiation [4]. UVC is absorbed in the stratosphere, and, therefore, only UVA and UVB reach the surface of the earth (95% UVA and 5% UVB approximately) [6]. ...
Article
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The skin is the main external organ. It protects against different types of potentially harmful agents, such as pathogens, or physical factors, such as radiation. Skin disorders are very diverse, and some of them lack adequate and accessible treatment. The photoaging of the skin is a problem of great relevance since it is related to the development of cancer, while psoriasis is a chronic inflammatory disease that causes scaly skin lesions and deterioration of the lifestyle of people affected. These diseases affect the patient’s health and quality of life, so alternatives have been sought that improve the treatment for these diseases. This review focuses on describing the properties and benefits of flavonoids from propolis against these diseases. The information collected shows that the antioxidant and anti-inflammatory properties of flavonoids play a crucial role in the control and regulation of the cellular and biochemical alterations caused by these diseases; moreover, flavones, flavonols, flavanones, flavan-3-ols, and isoflavones contained in different worldwide propolis samples are the types of flavonoids usually evaluated in both diseases. Therefore, the research carried out in the area of dermatology with bioactive compounds of different origins is of great relevance to developing preventive and therapeutic approaches.
... Thus the formulation base or penetration enhancers that enhance its penetration is required. 14 So liposomes were selected as drug carrier as they are ampihilic in nature and hydrophilic molecules can easily be embedded in the concentric bilayers. Liposomes being physiologically similar to the cell membrane are nontoxic in nature. ...
... It has been also reported that γ-linolenic acid has some cosmetic effects such as revitalizing the skin and slowing the aging process, and linoleic acid is used for the treatment of hyperplasia of the skin [36]. Phenolic compounds from microalgae are known to exhibit diverse activities such as antioxidant, antiallergic, anti-inflammatory, and UV protection functions [2,37]. ...
Article
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Recently, there has been emerging interest in various natural products with skin protective effects as they are recognized as safe and efficient. Microalgae have developed chemical defense systems to protect themselves against oxidative stress caused by UV radiation by producing various bioactive compounds including a number of secondary metabolites, which have potential for cosmeceutical applications. In addition, microalgae have various advantages as a sustainable source for bioactive compounds with diverse functions due to their rapid growth rate, high productivity, and use of non-arable land. In this study, we aimed to investigate the cosmeceutical potential of ethanol extract from Nannochloropsis sp. G1-5 (NG15) isolated from the southern West Sea of the Republic of Korea. It contained PUFAs (including EPA), carotenoids (astaxanthin, canthaxanthin, β-carotene, zeaxanthin, violaxanthin), and phenolic compounds, which are known to have various skin protective functions. We confirmed that the NG15 extract showed various skin protective functions with low cytotoxicity, specifically anti-melanogenic, antioxidant, skin-moisturizing, anti-inflammatory, anti-wrinkling, and UV protective function, by measuring tyrosinase inhibition activity; melanin content; DPPH radical scavenging activity; expression of HAS-2, MMP-1, and Col1A1 genes; and elastase inhibition activity as well as cell viability after UV exposure. Our results indicated that the NG15 extract has the potential to be used for the development of natural cosmetics with a broad range of skin protective functions.
... The rational use of these metabolites is a central topic for basic research and a major economic vector of naturalness for industries. [4][5][6] The huge molecular diversity of the flavonoids family arises from the succession of enzymatic reactions involving many enzymes of different classes. [7,8] The flavonoid biosynthesis belongs to the most intensively studied secondary metabolite pathways. ...
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Flavonoids are secondary metabolites ubiquitously found in plants. Their antioxidant properties make them highly interesting natural compounds to be used in pharmacology. Therefore, unravelling the mechanisms of flavonoids biosynthesis is a current hot challenge for the scientific community. Among all the enzymes involved in this biosynthetic pathway, DihydroFlavonol-4-Reductase (DFR) plays a key role on the way to the production of anthocyanins and proanthocyanidins. Here, we provide new information on the mechanism of action of this enzyme by using QM/MM-MD simulations applied to both dihydroquercetin (DHQ) and dihydrokaempferol (DHK) substrates. The consideration of these very similar compounds shed light on the major role played by the enzyme on the stabilization of the transition state but also on the activation of the substrate before the reaction through Near-Attack Conformer effects.
... Then, the auto-oxidative polymerization occurred from the unsaturated side chain. In addition, polyphenolic compounds such as flavonoids in the A. confusa heartwood extractives have antioxidant and free radical scavenging activities [28][29][30][31][32][64][65][66][67]. In the stage of autooxidative polymerization, the generated hydro-peroxide radicals (ROO *) were captured by the Ar-OH groups of polyphenols to produce hydro-peroxides (ROOH) and slowed the aerobic auto-oxidative polymerization, resulting in a delay of drying with heartwood extractive addition. ...
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In this study, a renewable polymeric material, refined oriental lacquer (ROL), used as a wood protective coating, and the Acacia confusa Merr. heartwood extractive, which was added as a natural photostabilizer for improving the lightfastness of ROL, were investigated. The best extract conditions for preparing heartwood extractives and the most suitable amount of addition (0, 1, 3, 5, and 10 phr) were investigated. The lightfastness index including brightness difference (ΔL *), yellowness difference (ΔYI), and color difference (ΔE *), and their applied properties of coating and film were measured. In the manufacture of heartwood extractives, the yield of extractives with acetone solvent was 9.2%, which was higher than that from toluene/ethanol solvent of 2.6%, and also had the most abundant total phenolic contents (535.2 mgGAE/g) and total flavonoid contents (252.3 μgRE/g). According to the SEM inspection and FTIR analysis, the plant gums migration to the surface of films and cracks occurred after UV exposure. The phenomena for photodegradation of ROL films were reduced after the addition of heartwood extractives. Among the different amounts of the heartwood extractives, the 10 phr addition was the best choice; however, the 1 phr heartwood extractive addition already showed noticeable lightfastness improvement. The drying times of ROL were extended and film performances worse with higher additions of heartwood extractives. Among the ROL films with different heartwood extractive additions, the ROL film with 1 phr addition had superior films properties, regarding adhesion and thermal stability, compared with the films of raw oriental lacquer.
... Some studies have shown the potential of CA in the treatment of inflammatory skin pathologies, such as psoriasis. Moreover, due to its antioxidant power, CA has photoprotective action against DNA damage, protecting the skin against aging and preventing melanoma [7][8][9][10]. ...
Article
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Caffeic acid (CA), a phenolic acid, is a powerful antioxidant with proven effectiveness. CA instability gives it limited use, so encapsulation in polymeric nanomaterials has been used to solve the problem but also to obtain topical hydrogel formulas. Two different formulas of caffeic acid liposomes were incorporated into three different formulas of carbopol-based hydrogels. A Franz diffusion cell system was used to evaluate the release of CA from hydrogels. For the viscoelastic measurements of the hydrogels, the equilibrium flow test was used. The dynamic tests were examined at rest by three oscillating tests: the amplitude test, the frequency test and the flow and recovery test. These carbopol gels have a high elasticity at flow stress even at very low polymer concentrations. In the analysis of the texture, the increase of the polymer concentration from 0.5% to 1% determined a linear increase of the values of the textural parameters for hydrogels. The textural properties of 1% carbopol-based hydrogels were slightly affected by the addition of liposomal vesicle dispersion and the firmness and shear work increased with increasing carbomer concentration.
... External aging and skin damage occur upon direct exposure to the external environment and are caused by environmental hazards, such as pollution, chemicals, smoking, and ultraviolet (UV) radiation [4,5]. UV radiation substantially contributes to various skin injuries and diseases, including skin aging and inflammatory skin diseases [6,7]. UV radiation induces intracellular ROS formation, causing widespread inflammatory damage from the epidermis to the dermis, resulting in accumulative skin damage, such as skin pigmentation and photoaging [8,9]. ...
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Reactive oxygen species (ROS) are generated during intrinsic (chronological aging) and extrinsic (photoaging) skin aging. Therefore, antioxidants that inhibit ROS production may be involved in delaying skin aging. In this study, we investigated the potential effects of compounds isolated from black ginger, Kaempferia parviflora, a traditional medicinal plant, on normal human dermal fibroblasts in the context of inflammation and oxidative stress. The isolated compounds were structurally characterized as 5-hydroxy-7-methoxyflavone (1), 3,7-dimethoxy-5-hydroxyflavone (2), 5-hydroxy-3,7,3,4-tetramethoxyflavone (3), 7,4-dimethylapigenin (4), 3,7,4-trimethylkaempferol (5), and 3,5,7-trimethoxyflavone (6), using nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography–mass spectrometry (LC/MS) analyses. These flavonoids were first evaluated for their ability to suppress extracellular matrix degradation in normal human dermal fibroblasts. Of these, 3,5,7-trimethoxyflavone (6) significantly inhibited the tumor necrosis factor (TNF)-α-induced high expression and secretion of matrix metalloproteinase (MMP)-1 by cells. We further found that 3,5,7-trimethoxyflavone suppressed the excessive increase in ROS, mitogen-activated protein kinases (MAPKs), Akt, and cyclooxygenase-2 (COX-2)and increased heme oxygenase (HO)-1 expression. The expression of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and IL-8, was also suppressed by 3,5,7-trimethoxyflavone (6). Taken together, our results indicate that 3,5,7-trimethoxyflavone (6) isolated from K. parviflora is a potential candidate for ameliorating skin damage.
... EGCG is the most active substance in tea polyphenols and has developmental value and excellent biological activities, including anticancer, antiviral, and anti-inflammatory activities [19][20][21]. Research has shown that, in the absence of selenium, EGCG can activate different antioxidant defense systems in the liver of mice to maintain the redox balance in the body [22]. Moreover, a previous study found that supplemental EGCG promoted the expression of Nrf2 in the intestinal mucosa of heat-stressed broilers [12]. ...
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This study evaluated epigallocatechin gallate’s (EGCG’s, 400 mg/kg) effect on meat quality and muscle antioxidant status of broilers under acute heat stress (AHS). A total of 144 21-day-old male Huainan partridge chickens were randomly allocated to the EGCG-free group (12 replicates) and the EGCG group (6 replicates). On day 94, the EGCG-free group was divided into the control group (CON) and the AHS group, and then AHS group and EGCG group (identified as AHS + EGCG group) were treated with AHS (33 ± 1 °C for 12 h). AHS increased (p < 0.05) L*24h, drip loss, muscle lactic acid, malondialdehyde (MDA) contents, and kelch-like ECH-associated protein 1 (Keap1) mRNA level, and decreased (p < 0.05) eviscerated percentage, pH24h, a*, muscle total superoxide dismutase (T-SOD) activity, the ratio of T-SOD/MDA and glutathione peroxidase /MDA, glycogen content, and nuclear factor erythroid 2-related 2 (Nrf2), catalase (CAT), NAD(P)H/quinone dehydrogenase 1 (NQO1) mRNA levels. The AHS + EGCG group exhibited lower (p < 0.05) L*24h, drip loss, muscle lactic acid, MDA contents and Keap1 mRNA level, and greater (p < 0.05) eviscerated percentage, pH24h, a*, muscle T-SOD activity, the ratio of T-SOD/MDA, Nrf2, and NQO1 mRNA levels compared with the AHS group. In conclusion, EGCG protects against AHS-impaired meat quality by improving muscle antioxidant capacity, which seems to be associated with the activation of the Nrf2 signaling pathway.
... Although the use of TiO 2 has been authorized since 1999 by the Food and Drugs Administration (FDA), recent studies revealed that nanoparticles of this inorganic material may lead to induced oxidative stress (Kim et al., 2010;Shrivastava et al., 2014), genotoxicity (Ghosh et al., 2010;Charles et al., 2018), and neurotoxic effects (Song et al., 2015). As polyphenols are natural pigments, these compounds are able to completely absorb the UV-B spectrum and partially the UV-A and UV-C spectra when applied topically, being a suitable replacer for TiO 2 nanoparticles (Nichols and Katiyar, 2010;Tomazelli et al., 2018). Studies analyzed in our work demonstrated the safety and efficiency of polyphenols present in coffee extracts through the absence of cytotoxic effects in mouse fibroblast (CCRF) and human epidermal keratinocyte (HaCaT) cell lines, and increase in SPF in cosmetic formulations (Choi et al., 2015;Cho et al., 2017;Sandoval et al., 2020). ...
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This systematic scoping review presents evidence from 52 primary research articles for the beneficial, and sustainable, use of coffee in personal care products. The identification and evaluation of natural ingredients that harbor bioactive compounds capable of supporting healthy personal care and protecting and improving the appearance and condition of skin and hair is topical. Demand for natural and sustainable ingredients in beauty and personal care products is driving growth in a market valued at over $500 billion. Coffee, as one of the world's favorite beverages, is widely studied for its internal benefits. External benefits, however, are less known. Here the potential of coffee and its by-products as ingredients in cosmetic and personal care formulations is explored. Diverse applications of a range of bioactive compounds from the coffee bean, leaves, and by-products, are revealed. Research is evaluated in light of economic and environmental issues facing the coffee industry. Many of the 25 million smallholder coffee farmers live in poverty and new markets may assist their economic health. Coffee by-products are another industry-wide problem, accounting for 8 million tons of residual waste per year. Yet these by-products can be a rich source of compounds. Our discussion highlights phenolic compounds, triacylglycerols, and caffeine for cosmetic product use. The use of coffee in personal care products can benefit consumers and industry players by providing natural, non-toxic ingredients and economic alternatives and environmental solutions to support sustainability within the coffee production chain. Database searches identified 772 articles. Of those included (k = 52), a minority (k = 10; N = 309) related to clinical trials and participant studies. Applications were classified, using the PERSOnal Care products and ingredients classification (PERSOC). Sustainability potential was evaluated with the Coffea Products Sustainability (COPS) model. Overall objectives of the systematic scoping review were to: (1) scope the literature to highlight evidence for the use of coffee constituents in externally applied personal care products, and (2) critically evaluate findings in view of sustainability concerns.
... The most popular approach in protecting the skin from UVR is the topical application of sunscreens [20]. However, to be effective, the use of topical sunscreen should be part of an integrated photoprotection strategy, including the use of oral photoprotective agents. ...
Article
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The increase in solar ultraviolet radiation (UVR) that reaches the Earth’s surface should make us reflect on the need to develop new approaches in protecting the skin from UVR exposure. The present study aims to evaluate the photoprotective and antiaging efficacy of a red orange extract (100 mg/day) in both Asian and Caucasian subjects. A randomized, double-blind, controlled study was carried out in 110 Asian and Caucasian subjects. Product efficacy was measured as follows: (1) the photoprotective effect was measured by the minimal erythema dose (MED) assessment; (2) the efficacy in decreasing the UVA+B-induced skin redness was measured by colorimetry; (3) the antioxidant efficacy was measured by the ferric-reducing antioxidant power (FRAP) and the malondialdehyde (MDA) assay; and (4) skin moisturization, skin elasticity, skin radiance, the intensity of melanin staining, transepidermal water loss (TEWL), and wrinkles were measured to assess the antiaging efficacy. The intake of the product for 56 days was effective in improving the skin reaction to UV exposure; in increasing the skin antioxidant capacity as well as in decreasing UVA-induced lipid peroxidation; in increasing the skin moisturization, skin elasticity, and skin radiance; and in decreasing TEWL, the intensity of melanin staining inside dark spots, and wrinkle depth. Our results suggest that the test product is effective in counteracting both the harmful effects of UVR exposure and aging signs.
... Other studies investigated the role of genistein against BC and found that it downregulated CDK-1 and inhibited the expression of Bcl-2, as well as the function of DNA polymerase II. They also found that genistein also increased the expression of p21 and p51 [103,155]. Genistein also showed inhibitory effects on tyrosine kinases and inhibited the cancer progression. Xie et al. [156] investigated that genistein is an effective therapeutic agent that inhibits DNA methylation in MCF-7 and MDA-MB-231 cells by blocking DNA methyltransferase activity. ...
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Citation: Naeem, M.; Iqbal, M.O.; Khan, H.; Ahmed, M.M.; Farooq, M.; Aadil, M.M.; Jamaludin, M.I.; Hazafa, A.; Tsai, W.-C. A
... Other studies investigated the role of genistein against BC and found that it downregulated CDK-1 and inhibited the expression of Bcl-2, as well as the function of DNA polymerase II. They also found that genistein also increased the expression of p21 and p51 [103,155]. Genistein also showed inhibitory effects on tyrosine kinases and inhibited the cancer progression. Xie et al. [156] investigated that genistein is an effective therapeutic agent that inhibits DNA methylation in MCF-7 and MDA-MB-231 cells by blocking DNA methyltransferase activity. ...
Article
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Breast cancer (BC) is the second leading cause of death among women, and it has become a global health issue due to the increasing number of cases. Different treatment options, including radio-therapy, surgery, chemotherapy and anti-estrogen therapy, aromatase inhibitors, anti-angiogenesis drugs, and anthracyclines, are available for BC treatment. However, due to its high occurrence and disease progression, effective therapeutic options for metastatic BC are still lacking. Considering this scenario, there is an urgent need for an effective therapeutic strategy to meet the current chal-lenges of BC. Natural products have been screened as anticancer agents as they are cost-effective, possess low toxicity and fewer side effects, and are considered alternative therapeutic options for BC therapy. Natural products showed anticancer activities against BC through the inhibition of angiogenesis, cell migrations, proliferations, and tumor growth; cell cycle arrest by inducing apoptosis and cell death, the downstream regulation of signaling pathways (such as Notch, NF-κB, PI3K/Akt/mTOR, MAPK/ERK, and NFAT-MDM2), and the regulation of EMT processes. Natural products also acted synergistically to overcome the drug resistance issue, thus improving their ef-ficacy as an emerging therapeutic option for BC therapy. This review focused on the emerging roles of novel natural products and derived bioactive compounds as therapeutic agents against BC. The present review also discussed the mechanism of action through signaling pathways and the synergistic approach of natural compounds to improve their efficacy. We discussed the recent in vivo and in vitro studies for exploring the overexpression of oncogenes in the case of BC and the current status of newly discovered natural products in clinical investigations.
... Replacing synthetic filters with natural, sustainable, and non-toxic molecules had also been considered. Natural polyphenols not only are potential skin protectors with high antioxidant abilities, but they also absorb at UV light wavelengths, exhibit SPF boosting properties (Stevanato et al., 2014;de Alencar Filho et al., 2016), repair DNA (Nichols and Katiyar, 2010), and rarely give sensitization effects probably because they are components of the diet. For instance, apigenin, caffeic acid, and resveratrol were found to exhibit interesting sun protection factors (SPF) of 28.8, 28.0, and 19.2 respectively, at only 7% (w/v) concentration (Stevanato et al., 2014), as well as other known flavonoids (de Alencar Filho et al., 2016). ...
Article
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Sunscreen oil-in-water emulsions containing few ingredients and two EU-authorized organic filters had been developed in an eco-friendly approach. Based on their photostability, spectroscopic features, and the lack of data on toxicity, BEMT (UVA/B range; bis-ethylhexyloxyphenol methoxyphenyl triazine) and DHHB (UVA; diethylamino hydroxybenzoylhexyl benzoate) were selected and incorporated at minimal concentrations to reduce the risk of impact on human health and coastal marine ecosystems. Despite the inconclusive results previously reported, the use of the w-soluble and largely available Na-lignosulfonate (LiS) had been reconsidered with success. Since BEMT and DHHB alone or in combination were not able to higher the sun protection factor (SPF) value at 50, results showed that it becomes possible by supplementing with LiS at 5% (w/w), ensuring stability, antiradical property, and a non-toxicity of the sun emulsion. After defining the range doses for the three components, minimizing concentrations was achieved by experimental design studies using a response surface methodology in which SPF values before and after irradiation has been considered. Consequently, an SPF30 and SPF50 emulsions containing only 9 and 12% total filter respectively and 5% LiS each had been developed. This high boosting effect led to discussions on how LiS interacts, suggesting the involvement of J aggregation, the formation of LiS micelles that would partly encapsulate the o-soluble filters, and the mode of adsorption at the solid-liquid interface of the poly(methyl-methacrylate) plate or the skin.
... Oxidative stress has been linked to various types of diseases [5,36,37]. Previous studies have reported on several natural compounds with antioxidant and cell-protective activities [38,39]. For example, cynaropicrin induces the translocation of AhR into the nucleus (by binding to it) and activates the Nrf2 signaling pathway; this protects cells from ROS-mediated oxidative damage [40]. ...
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Tomentosin, one of natural sesquiterpene lactones sourced from Inula viscosa L., exerts therapeutic effects in various cell types. Here, we investigated the antioxidant activities and the underlying action mechanisms of tomentosin in HaCaT cells (a human keratinocyte cell line). Specifically, we examined the involvement of tomentosin in aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Treatment with tomentosin for up to 60 min triggered the production of reactive oxygen species (ROS), whereas treatment for 4 h or longer decreased ROS production. Tomentosin treatment also induced the nuclear translocation of Nrf2 and upregulated the expression of Nrf2 and its target genes. These data indicate that tomentosin induces ROS production at an early stage which activates the Nrf2 pathway by disrupting the Nrf2–Keap1 complex. However, at a later stage, ROS levels were reduced by tomentosin-induced upregulation of antioxidant genes. In addition, tomentosin induced the phosphorylation of mitogen-activated protein kinases (MAPKs) including p38 MAPK and c-Jun N-terminal kinase (JNK). SB203580 (a p38 MAPK inhibitor) and SP600125 (a JNK inhibitor) attenuated the tomentosin-induced phosphorylation of Nrf2, suggesting that JNK and p38 MAPK signaling pathways can contribute to the tomentosin-induced Nrf2 activation through phosphorylation of Nrf2. Furthermore, N-acetyl-L-cysteine (NAC) treatment blocked both tomentosin-induced production of ROS and the nuclear translocation of Nrf2. These data suggest that tomentosin-induced Nrf2 signaling is mediated both by tomentosin-induced ROS production and the activation of p38 MAPK and JNK. Moreover, tomentosin inhibited the AhR signaling pathway, as evidenced by the suppression of xenobiotic-response element (XRE) reporter activity and the translocation of AhR into nucleus induced by urban pollutants, especially benzo[a]pyrene. These findings suggest that tomentosin can ameliorate skin damage induced by environmental pollutants.
... In our experimental model, the pretreatment with C. sinensis extract was able to reduce the deleterious effects of UVB radiation by increasing mRNA and protein expression of type 1 collagen and elastin in HFF1 cells and concomitantly decreasing, in both cell lines, the MMP1 and MMP9 protein and mRNA expression levels with respect to irradiated control cells (Figures 8 and 9). Previous studies demonstrated that in addition to vitamin C, polyphenols, particularly flavonoids, also increased collagen and elastin content and inhibit MMP expression in cell cultures [11,40]. ...
Article
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Excessive exposure to solar radiation is associated with several deleterious effects on human skin. These effects vary from the occasional simple sunburn to conditions resulting from chronic exposure such as skin aging and cancers. Secondary metabolites from the plant kingdom, including phenolic compounds, show relevant photoprotective activities. In this study, we evaluated the potential photoprotective activity of a phytocomplex derived from three varieties of red orange (Citrus sinensis (L.) Osbeck). We used an in vitro model of skin photoaging on two human cell lines, evaluating the protective effects of the phytocomplex in the pathways involved in the response to damage induced by UVA-B. The antioxidant capacity of the extract was determined at the same time as evaluating its influence on the cellular redox state (ROS levels and total thiol groups). In addition, the potential protective action against DNA damage induced by UVA-B and the effects on mRNA and protein expression of collagen, elastin, MMP1, and MMP9 were investigated, including some inflammatory markers (TNF-α, IL-6, and total and phospho NFkB) by ELISA. The obtained results highlight the capacity of the extract to protect cells both from oxidative stress—preserving RSH (p < 0.05) content and reducing ROS (p < 0.01) levels—and from UVA-B-induced DNA damage. Furthermore, the phytocomplex is able to counteract harmful effects through the significant downregulation of proinflammatory markers (p < 0.05) and MMPs (p < 0.05) and by promoting the remodeling of the extracellular matrix through collagen and elastin expression. This allows the conclusion that red orange extract, with its strong antioxidant and photoprotective properties, represents a safe and effective option to prevent photoaging caused by UVA-B exposure.
... Therefore, TiO 2 is coated with other materials before introduction into the sunscreen product [15]. With the escalating number of reports on the adverse effects related to the synthetic sunscreen agents, the recent development in this field is the usage of herbs comprising natural compounds with UV-absorbing property and thereby to reduce and/or minimize the use of synthetic sunscreen products [19,20]. ...
... Anyhow, more and more reports have shown that polyphenols containing flavonoids powerfully protect skin from the risk of UV-induced skin cancers via mitigating cutaneous inflammation, OS, LPO and DNA damage [117]. Therefore, flavonoids would be a potential alternative for skin cancers, particularly UV-induced cutaneous carcinoma. ...
Article
Background: Skin, as a crucial external defense organ, is more vulnerable to oxidative stress (OS) insult, reactive oxygen species (ROS)-mediated OS in particular. OS results from a redox imbalance caused by various extrinsic stimuli and occurs once the oxidants production overwhelming the antioxidants capacity, through mediating in DNA damage, lipid peroxidation (LPO), protein oxidation and a serial of signaling pathways activation/inactivation, thereby offering favorable conditions for the occurrence and development of numerous diseases especially some dermatoses, e.g. psoriasis, vitiligo, skin photodamage, skin cancer, systemic sclerosis (SSc), chloasma, atopic dermatitis (AD), pemphigus, etc. Targeting OS molecular mechanism, a variety of anti-OS agents emerge, in which flavonoids, natural plant extracts, stand out. Objectives: To discuss the possible mechanisms of OS mediating in dermatoses and summarize the properties of flavonoids as well as their applications in OS-related skin disorders. Methods: Published papers on flavonoids and OS-related skin diseases were collected and reviewed via database searching on PubMed, MEDLINE and Embase, etc. Results: It has been confirmed that flavonoids, belonging to polyphenols, are a class of plant secondary metabolites widely distributed in various plants and possess diverse bioactivities especially their potent antioxidant capacity. Moreover, flavonoids benefit to suppress OS via eliminating free radicals and mediating the corresponding signals, further excellently working in the prevention and management of OS-related skin diseases. Conclusion: Flavonoids have the potential therapeutic effects on oxidative stress-related dermatoses. However, more studies on specific mechanism as well as the dosage of flavonoids are needed in future.
... 7 GSE as a natural antioxidant was found to be a potent reactive oxygen species (ROS)-scavenger and effective anti-inflammatory agent confirmed through various in vitro assays. 8,9 In our recent study, it was found that GSE, while exhibiting low cytotoxicity, stimulated skin fibroblasts proliferation, and possessed UVA-photoprotection of skin fibroblasts. 7 GSE and GSE-derived flavonoids were also reported to inhibit an overexpression of matrix metalloproteinases (MMPs) improving the interaction between fibroblasts and extracellular matrix (ECM), and consequently normalizing the production of collagen. ...
Article
Background: Asian skin undergoing chronological aging, accumulates signs of photoaging mediated by prolonged exposure to ultraviolet (UV) radiation. Although sunscreens are effective in preventing signs of photoaging, polyphenol-rich extracts e.g., grape seed extract (GSE) can provide additional protection through the broad spectrum of biological activities. Aims: To access the effectiveness of a sunscreen formulation containing GSE as an important cosmetic ingredient for the improvement of age-related changes in Asian skin using noninvasive evaluation techniques. Methods: Noninvasive methods were used to assess changes in the biophysical properties corresponding to aging signs including melanin and erythema indices, color parameters of the CIE L*a*b* system, elasticity, and hydration of the forearm skin before and after applying the sunscreen with GSE. In addition, to confirm the effectiveness of the tested product, we compared it with benchmark sunscreen, and a cream base containing either GSE or UV filters. Results: Twice-daily application of sunscreen containing 3% GSE significantly reduced the level of melanin and erythema and improved overall skin tone. The hydration was drastically increased after 3 hours of wearing formulation and was maintained relatively high for 5 hours. Skin elasticity parameters, including Young's modulus, retraction time, and viscoelasticity improved in participants of all age categories (35-59 years). Moreover, sunscreen with GSE, as acclaimed by participants, improved overall skin appearance. Conclusions: The balancing potential of GSE on the skin, combined with the photoprotective properties of UV filters demonstrated an added value as an anti-aging agent and proved efficacy for both photoaged and chronologically aged Asian skin.
... Apart from cereal use, the application of CF based on antioxidant properties has attracted increasing attention [28][29][30]35]. Polyphenols are well-known antioxidants and skin protectors by possessing strong free radical scavenging activity [36], reducing inflammation and absorbing UV radiation to provide skin photoprotection [37,38]. Rutin is a flavonoid widely distributed in fruits and vegetables and the representative polyphenol in CF indicated by previous studies [21,22]; several reports have demonstrated the biological effects of rutin on ROS-induced skin aging [39] and suggested that rutin effectively inhibits the formation of AGEs on collagen synthesis [40]. ...
Article
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Skin aging is a complex process involving photoaging and glycation stress, which share some fundamental pathways and have common mediators. They can cause skin damage and collagen degradation by inducing oxidative stress and the accumulation of reactive oxygen species (ROS). Chenopodium formosanum (CF), also known as Djulis, is a traditional cereal in Taiwan. This study investigated the protection mechanisms of CF extract against ultraviolet (UV) radiation and advanced glycation end products (AGEs)-induced stress. The results indicated that CF extract had strong antioxidant and free radical scavenging effects. It could reduce UV-induced intracellular ROS generation and initiate the antioxidant defense system by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway in human skin fibroblasts. CF extract modulated mitogen-activated protein kinase (MAPK) and transformed growth factor-beta (TGF-β) signaling pathways to alleviate oxidative stress-induced skin aging. Moreover, the results revealed that CF extract not only promoted collagen synthesis but also improved aging-induced collagen degradation. CF extract attenuated AGEs-induced ROS production and the upregulation of receptor for AGEs (RAGE). The overall results suggest that CF extract provides an effective anti-aging strategy by preventing skin damage from oxidative stress and collagen loss with potent antioxidant, anti-photoaging, and antiglycation activities.
... Chronic UV radiation exposure, on the other hand, increases reactive oxygen species (ROS) formation, which causes inflammation, photoaging, erythema, and skin cancer [33], [34]. As a result, UV radiation protection for the skin is critical for mitigating UV radiation-induced oxidative damage [35], [36]. Silk sericin is a glycoprotein that aids in cocoon production and protects the pupa and fibroin from UV-induced oxidative damage [37]. ...
Article
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Because of its adequate biological and mechanical properties, sericin has been considered for different applications. Sericin is found to have anti-tumoral properties against colon cancer, mechanical properties, as well as anticoagulant and cryoprotective properties. According to these findings, sericin is a significant component of the health industry. Silk sericin exhibits biodegradability, non-toxicity, oxidation resistance, UV resistance, and moisturizing characteristics. The present review is mainly focused on considering the mechanical and biological characteristics of silk sericin, as well as its applications in many industries, especially in the medical industry. In addition, one of the most notable limitations of sericin forms in many application fields is their lack of mechanical properties. Better crystallinity and a longer molecular chain result in improved mechanical properties. Additionally, mechanical properties are influenced by the macromolecular structure, notably porosity. The textile silk procedure has the ability to influence the features of sericin samples, such as thermal stability and structure. Therefore, the present study reviews the past works on the improvement solutions of the mechanical characteristics of sericin.
... Both omega -3 and omega -6 fatty acids are important cell membrane components, essential for the function of epidermal barrier; they exhibit anti-inflammatory and anti-allergic effects, enhance repair processes and soothe irritation [87]. Plant polyphenols are considered as important substances for skin function, with hydrating, smoothing and softening effects [88][89][90]. Additionally, they soothe irritation and reduce the redness of skin, accelerating the natural regeneration of the epidermis, stabilizing the capillaries, improving microcirculation and elasticity in the skin and protecting against harmful external factors [87]. ...
Article
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This study aimed to evaluate the long-term dietary effects of dried olive pulp (OP) on production performance, fatty acid profile and health lipid indices and quality characteristics of produced eggs, health and welfare indicators of laying hens. It was carried out in a commercial poultry farm using 300 Isa Brown layers at 23 weeks of age. The hens were randomly and equally divided in six dietary groups CON, OP2, OP3, OP4, OP5 and OP6, according to the inclusion rate of OP in the ration (0%, 2%, 3%, 4%, 5% and 6%, respectively). OP feeding increased the percentage of polyunsaturated fatty acids (PUFA) in eggs, decreased that of saturated fatty acids (SFA) and improved the PUFA to SFA ratio and health lipid indices, as indicated by the decrease of AI and TI and the increase in the h/H ratio of produced eggs, in a dose-dependent way. OP-fed layers presented a lower percentage of broken eggshells compared to controls. No adverse effects on birds’ performance, egg quality traits, health and welfare parameters were observed but a positive impact on Keel Bone Damage (KBD) incidence and belly plumage damage was recorded. OP feeding at the rates of 5% and 6% seems to be beneficial in improving egg nutrition quality.
... Various botanical extracts that claim to reduce skin aging and enhance the health of the skin are commercially available (Argyropoulou et al. 2013;Cavinato et al. 2017;Li et al. 2009;Mukherjee et al. 2011). Some medicinal plants have several constituents with antioxidant properties, such as polyphenols (Nichols and Katiyar 2010), alkaloids (Beak et al. 2004), tannins (Gali-Muhtasib et al. 2000), carotenoids, and flavonoids (Stahl and Sies 2007). Sorbaria kirilowii (Regel) Maxim, which is a common plant with a wide distribution, especially in East Asia, is used to beautify the environment and is a component of traditional medicine in the East. ...
Article
Sorbaria kirilowii (Regel) Maxim, a plant found in China, Korea, Japan, and east of Europe, is a common herb used for traditional medicinal purposes. However, its ability to prevent photoaging has not been studied. In this study, we investigated the anti-photoaging functions of an ethanol extract (Sk-EE) of S. kirilowii (Regel) Maxim using human keratinocytes exposed to UVB. First, we analyzed the cytotoxicity of Sk-EE. Then, we determine the expression of genes related to inflammation, collagen degradation, and moisture retention. We also explored the anti-pho-toaging mechanism of Sk-EE by determining correlated signaling pathways and target molecules using reporter gene assays and immunoblotting analyses. Sk-EE treatment of cells increased hyaluronic acid synthase (HAS), filaggrin (FLG), and collagen type I alpha 1 (COL1A1) expression. Sk-EE dose-dependently inhibited the UVB-induced expression of matrix metalloproteinases (MMPs) 1, 2, 9 and cyclooxygenase (COX)-2 by blocking the activator protein (AP)-1 signaling pathway, in particular the phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular response kinase (ERK). In addition, c-Fos and c-Jun were targeted by Sk-EE. Our results indicate that Sk-EE has anti-inflammatory and skin-protective properties, and could be a candidate to treat signs of photoaging.
... Natural-based products belonging to the family of polyphenols encompass a large variety of vegetables, fruits, as well as nuts, seeds, bark, and flowers. This family provides an important source of dietary AOs, anti-inflammatory and potentially anticancer prod-ucts [278]. Some of the key members of this family include flavonoids, phenolic acids, and stilbenes. ...
Article
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Reactive oxygen species (ROS) are necessary for normal cell signaling and the antimicrobial defense of the skin. However excess production of ROS can disrupt the cellular redox balance and overwhelm the cellular antioxidant (AO) capacity, leading to oxidative stress. In the skin, oxidative stress plays a key role in driving both extrinsic and intrinsic aging. Sunlight exposure has also been a major contributor to extrinsic photoaging of the skin as its oxidising components disrupt both redox- and iron-homeostasis, promoting oxidative damage to skin cells and tissue constituents. Upon oxidative insults, the interplay between excess accumulation of ROS and redox-active labile iron (LI) and its detrimental consequences to the skin are often overlooked. In this review we have revisited the oxidative mechanisms underlying skin damage and aging by focussing on the concerted action of ROS and redox-active LI in the initiation and progression of intrinsic and extrinsic skin aging processes. Based on these, we propose to redefine the selection criteria for skin antiaging and photoprotective ingredients to include natural antioxidants (AOs) exhibiting robust redox–balancing and/or iron-chelating properties. This would promote the concept of natural-based or bio-inspired bifunctional anti-aging and photoprotective ingredients for skincare and sunscreen formulations with both AO and iron-chelating properties.
... After exposure to sunlight, melanocytes develop more dendrites, contain more melanosomes, and increase the rate of melanin transference to the keratinocytes. This provides decreasing absorption of UV radiation by DNA and cellular components (Nichols & Katiyar, 2010;Venus et al., 2010). ...
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The skin is a barrier between the internal and external environment of an organism. Depending on the species, it participates in multiple functions. The skin is the organ that holds the body together, covers and protects it, and provides communication with its environment. It is also the body's primary line of defense, especially for anamniotes. All vertebrates have multilayered skin composed of three main layers: the epidermis, the dermis, and the hypodermis. The vital mission of the integument in aquatic vertebrates is mucus secretion. Cornification began in amphibians, improved in reptilians, and endured in avian and mammalian epidermis. The feather, the most ostentatious and functional structure of avian skin, evolved in the Mesozoic period. After the extinction of the inosaurs, birds continued to diversify, followed by the enlargement, expansion, and diversification of mammals. Which brings us to the most complicated skin organization of mammals with differing glands, cells, physiological pathways, and the evolution of hair. Throughout these radical changes, some features were preserved among classes such as basic dermal structure, pigment cell types, basic coloration genetics, and similar sensory features which enable us to track the evolutionary path. The structural and physiological properties of the skin in all classes of vertebrates are presented. The purpose of this review is to go all the way back to the agnathans and follow the path step by step up to mammals to provide a comparative large and updated survey about vertebrate skin in terms of morphology, physiology, genetics, ecology, and immunology. https://anatomypubs.onlinelibrary.wiley.com/doi/abs/10.1002/ar.24908
... Banyaknya manfaat yang dimiliki oleh lendir bekicot dalam pengobatan tradisional dan kosmetik, mendukung untuk dilakukan penelitian tentang aktivitas antioksidan dan tabir surya pada lendir bekicot karena selain lendir bekicot memiliki banyak manfaat untuk kulit, kulit juga merupakan pembatas tubuh dari lingkungan sekitar (Fox et al., 2011) secara langsung dari paparan sinar UV matahari yang merupakan inisiator pembentukan ROS (Reactive Oxygen Species) pada kulit (Nichols and Katiyar, 2010). ...
Article
Photoaging refers to the extrinsic aging resulting from ultraviolet (UV) irradiation, which impacts skin appearance and is accompanied by the risk of skin carcinoma. Developing natural products as photoprotective agents is of great interest in cosmetic industry nowdays. The present study aimed at investigating the possible use of Artemisia sieversiana Ehrhart essential oil (AEO) for the prevention of photoaging induced by UVB. AEO was characterized by chamazulene, which accounted for 38.92% among total 51 identified compounds. In in vitro assays, AEO was found to be a moderate antioxidant and good UVB filter with photostability. A UVB-induced photoaging mice model was established with three AEO formulations (0.1%, 0.5% and 1.5%, w/w) topically applied prior to UVB irradiation. The activities of catalase (CAT), particularly superoxide dismutase (SOD) of skin increased, while malondialdehyde (MDA) content decreased in AEO groups as compared to model controls. The production of matrix metalloproteinases (MMP-1 and MMP-3), depletion of hydroxyproline (HYP) in skin was inhibited by AEO in a dose dependent manner. Histological evaluation indicated that AEO decreased epidermal thickness, inflammatory cell infiltration, collagen degradation and elastin aberrance. These findings indicated that AEO could be a promising sunscreen agent in protecting skin against photoaging.
Article
Acanthopanax senticosus has been used to extract active products. However, abundant Acanthopanax senticosus residues (ASR), which contain plenty of lignin are discarded after extraction. An appropriate extraction method should be chosen to obtain the lignin with such desirable properties. Thus, this study investigated the effect of alkali, milled wood, deep eutectic solvent and ethanol methods on the lignin. Lignin obtained from different extraction methods were characterized, yields, chemical structure, thermal behavior, molecular weight and phenolic content were evaluated. The results show that the process of lignin acquisition has a great influence on the properties of lignin. Moreover, the multifarious functional groups exist in lignin macromolecules, such as phenolic, ether groups and other chromophores, conferred good UV resistance to lignin. Among them, the lignin from alkali method has the most phenolic-OH groups and smallest molecular weight result in a good UV-resistant, the SPF value achieves 2.39 at 1% AL content, the alkali method was the best way to make sunscreen blended with cream take various factors into consideration. This study used lignin as a bioactive ingredient to provide UV-resistant property to sunscreen formulations. Furthermore, lignin extracted from Acanthopanax senticosus residue provides a new application for the treatment of herb residue waste.
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In this study, the biological activities of four extracts from Vitis vinifera by-products: two pomace extracts, white (WPE) and red (RPE), a canes extract (CE), and their combination (CoE), were evaluated, to be included in freeze-drying mouthwashes formulations. The cytocompatibility and anticancerous potential of the four extracts were tested on three cancerous cell lines, as well as the cytoprotective activity against nicotine-induced cytotoxicity and the antioxidant potential determined on a human gingival fibroblasts (HGF) cell line. Additionally, the anti-inflammatory activity and the antimicrobial activity against several microorganisms from the oral microbiome were tested. Freeze-dried mouthwashes with CoE were prepared and characterized, both as lyophilizates and after reconstitution. The four tested extracts showed the highest cytotoxicity on MDA-kb2 cell line. The antioxidant potential was demonstrated for WPE, RPE, CE, and CoE, both in non-stimulated and H2O2 stimulated conditions. The four extracts reduced the levels of proinflammatory cy-tokines (IL-6, IL-8, and IL-1β) in a dose-dependent manner, confirming their anti-inflammatory activity. The antimicrobial activity of tested extracts was shown against pathogenic bacteria from the oral microbiome. Mouthwashes of CoE with poloxamer-407, xylitol, and different ratios of mannitol were prepared by freeze-drying leading to porous formulations with interesting mechanical properties and reconstitution times.
Article
BACKGROUND: As the interest in foods with positive effects on human health has increased in recent decades, the importance of the mineral contents and oil compositions of grape seeds has been better understood. However, research on grape seeds to date has largely focused on effects on health and the usability of grape seeds in the food industry and animal feeds. In agricultural research, grape seeds have generally been evaluated as a source of genes in breeding new varieties and as propagation material. OBJECTIVE: Unlike previous studies, this study not only investigates the effect of variety on the changes of pomological properties, fatty acid compositions, and oil, protein, and mineral contents of grape seeds; it also aims to determine the effects of grape rootstocks and growing seasons on those changes. METHODS: The seeds of five grape varieties (Red Globe, Trakya Ilkeren, Ata Sarisi, Hatun Parmagi, and Horoz Karasi) grafted onto drought-tolerant grape rootstocks (1103P and 110R) were analyzed during the growing seasons of 2017 and 2018. RESULTS: Seed size, moisture and oil contents, major fatty acids (palmitic, oleic, and linoleic), and levels of saturated fatty acids, monounsaturated fatty acids, unsaturated fatty acids, and boron varied by variety, rootstock, and season. However, the effects of growing seasons and varieties on the seeds were not limited to these findings; effects were also seen for seed vitality, protein content, and N, K, Ca, and Fe levels of the seeds, among others. CONCLUSIONS: Genotype was found to be the main factor causing changes in the fatty acid compositions and mineral contents of grape seeds. When the factors that we investigated were ordered based on the changes they caused for seeds in general, the sequence that appeared was genotype > growing season > grape rootstock.
Article
Lotus root is a traditional food ingredient used primarily in Asia and is rich in polyphenols. To determine its potential use in antiphotoaging, polyphenols were extracted from lotus root with 50% ethanol, and the activity of matrix metalloproteinase (MMP) was measured in dermal cells treated with ultraviolet A (UVA). UVA exposure increased the gene expression of IL-1α, the mRNA levels of MMP-1, and hence, the levels of MMP-1 protein in HaCaT cells, whereas cells treated with lotus polyphenol (LP) normalized these values to the control. In the presence of LP at concentrations of 1 and 10 μg/mL, both the secretion of IL-1α and protein levels of MMP-1 in human keratinocyte cells significantly reduced. Similarly, in the LabCyte EPI-MODEL24, irradiation with UVA caused an increase in mRNA expression of IL-1α and MMP-1, which was prevented by adding LP to the cells. Our results with three different skin cells accordingly showed that LP may help maintain skin health through decreased levels of MMP-1 activity via its anti-inflammatory properties.
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Vegetable oils have been suggested in polymer science as an environmentally friendly feedstock existing in abundance in nature, with worldwide availability and low cost. Although they have been widely explored as building blocks for polymers synthesis, their functional roles as owners of potent biomolecules are less unexplored. Their ancient biomolecules support natural biological roles such as antioxidant, antibacterial, anti-inflammatory, and anti-tumor properties, which are considered a great promise for biomedical proposes. This comprehensive review provides an overview of grape, soybean, castor, sesame, olive vegetable oils where their native anti-inflammatory, anti-tumor, antioxidant, and antibacterial biological compounds bring health benefits that can be translated to the biomedical field. These plant oils are considered the most relevant for the molecular design of functional and high-performance biomaterials that can contribute to the reduction of carbon footprint. The representative examples of vegetable oil-derived biomaterials, their main composition, shape, and the processing technology will be covered and innovative strategies toward the development of new multifunctional polymeric materials for pharmacological patches, wound healing devices, drug carriers, and scaffolds for tissue engineering applications will be discussed.
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Burn injuries are underappreciated injuries associated with substantial morbidity and mortality. Overexposure to ultraviolet (UV) radiation has dramatic clinical effects in humans and is a significant public health concern. Although the mechanisms underlying UVB exposure are not fully understood, many studies have made substantial progress in the pathophysiology of sunburn in terms of its molecular aspects in the last few years. It is well established that the transient receptor potential ankyrin 1 (TRPA1), and vanilloid 1 (TRPV1) channels modulate the inflammatory, oxidative, and proliferative processes underlying UVB radiation exposure. However, it is still unknown which mechanisms underlying TRPV1/A1 channel activation are elicited in sunburn induced by UVB radiation. Therefore, in this review, we give an overview of the TRPV1/A1 channel-mediated signalling cascades that may be involved in the pathophysiology of sunburn induced by UVB radiation. These data will undoubtedly help to explain the various features of sunburn and contribute to the development of novel therapeutic approaches to better treat it.
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Polyphenols are a class of compounds widely existing in living species ranging from plants, fungi, bacteria to animals, and possess various interesting functions such as anti-inflammatory, immunomodulatory, anti-oxidative and anti-ultraviolet...
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For the first time, the photoprotective potential (UV absorption and antioxidant properties) of Protium spruceanum leaves and its main flavonoids was investigated combining an in vitro and in silico approach. The extract was standardized in rutin content (0.8% w/w), quantified by a validated HPLC-DAD method. The extract protected fibroblasts and keratinocytes against cell death in the stress oxidative H2O2-induced test, with greater effect than rutin standard. This cytoprotection is correlated to the free radical scavenging action, determined by DPPH method. The theoretical investigation on the UV absorption showed an excellent correlation of the results (R² = 0.911) allowing valuable information about the photoprotective properties of rutin, afzelin and quercitrin, as the importance of the A, B and C rings in the UV absorption property and the hydroxyls in B ring (catechol group) leading to a better antioxidant action. Therefore, the extract from P. spruceanum leaves is a promising candidate for sunscreen development.
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The atopic dermatitis (AD) complex pathogenesis mechanism reveals marked changes of certain signaling factors as well as some morphological alterations in the epidermis. Reduced resilience against environmental factors and oxidative stress often makes the treatment with corticosteroids or tacrolismus ointments indispensable. In view of the correlation between oxidative stress and AD pathological factors, antioxidants can be incorporated into AD management strategies. This study investigates a curly kale, apple and green tea-containing natural extract rich in antioxidants for its effects on signaling inflammatory molecules and skin barrier enhancement in human epidermal keratinocytes- (NHEKs) based cell assays. Furthermore, the skin penetration on porcine ears was measured ex vivo using Raman micro spectroscopy. Finally, in a double-blind half-side, placebo-controlled clinical study, the effects of a formulation containing this extract were analyzed for the influence of lesion severity, epidermal barrier function, and pruritus in mild to moderately AD patients. Summarizing our results: The extract reduces expression of inflammatory cytokines in keratinocytes and increases barrier-related molecules. The verum formulation with a very high antioxidant capacity used in AD patients with mild to moderate lesions reduces itching, local SCORAD, and improves barrier function and the hydration of skin lesions.
Thesis
In recent years, the scientific community has seen an increasing interest in the use of natural compounds in medicines, food supplements, cosmetics and dermatological products. An important example is Sambucus nigra L. whose flowers (elderflowers) and berries (elderberries) have been widely used in traditional medicine. The traditional use of elderflowers in the relief of early symptoms of common cold has been officially recognised by the European Union, where several products in the form of herbal tea, tincture or liquid extract, are available on the market. Elderberries have also been traditionally used in the form of herbal tea, syrup or juice. Nevertheless, no single herbal substance/herbal preparation is registered as medicine. In line with the need for comprehensive pharmacological studies to validate the traditional use of S. nigra, namely its anti-inflammatory activity, one of the aims of this PhD thesis was to screen and characterize biological activities of S. nigra L. extracts obtained using different extraction methodologies. Then, to optimize the biological activity of the best extract (i.e. with high interest for therapeutic uses), different extract-loaded nanocarriers were prepared. Different materials were applied in this task such as polymeric and lipid-based materials. In this specific context, the purpose of using nanotechnology as strategy was to increase the stability of bioactive compounds and to modulate their release, creating a potential topical formulation. Due to the harvesting time of elderflowers and elderberries, in a first part of this PhD thesis, initial nanoencapsulation studies were performed using hyaluronic acid as model drug. Hyaluronic acid is commonly used through intraarticular administration for viscosupplementation in osteoarthritis and other inflammation disorders. Therefore, the first studies consisted of producing an characterising polymeric nanoparticles made of poly(lacticco-glycolic acid) (PLGA) were prepared with and without hyaluronic acid. The inclusion of hyaluronic acid was achieved with an efficiency higher than 70%, but resulted in a marked particle size increase. Particles revealed an in vitro sustained release profile and in vitro cell compatibility, as well as a risk of haemolysis less than 1%, ensuring their safety. In vivo antiinflammatory studies showed a higher inhibition for hyaluronic acid-loaded PLGA particles when compared to hyaluronic acid suspension (78% versus 60%). Results were not so different from the positive control, clearly suggesting that this formulation may be a promising alternative to the current hyaluronic acid injectable dosage form. Having characterised the intended particulate carrier, different extraction methods were studied to obtain the S. nigra extracts from elderflowers and elderberries. For this purpose, fresh flowers, and fresh and dried berries were considered, resulting in eighteen S. nigra extracts. Several parameters were considered for selecting the extraction method, i.e. yield of extraction, type of solvent, flavonoid content and biological activity of the resultant extracts (antioxidant activity, total polyphenol content, collagenase, elastase, tyrosinase and acetylcholinesterase inhibition). The most promising extracts were characterized for in vitro and in vivo antiinflammatory activity and cytotoxicity (skin and monocytic cells). The most promising extracts were those obtained from fresh flowers using ultrasounds method with methanol. Specifically, these extracts showed results similar to positive controls, particularly the antioxidant activity (75 ± 2%), collagenase inhibition (94 ± 1%) and in vitro anti-inflammatory activity (97 ± 3%). Nevertheless, extracts of fresh flowers using ultrasounds/ethanol presented higher collagenase inhibition (88 ± 3%) and in vitro anti-inflammatory activity (102 ± 2%). Cytotoxicity testing confirmed their safety. The second aim of the present PhD thesis was to optimize the activity of the resultant methanolic extracts through encapsulation in different types of nanocarriers: polymeric nanoparticles based on PLGA and poly-Ɛ-caprolactone (PCL) and lipid-based nanoparticles (ethosomes). The so obtained nanoparticulate formulations were analysed in terms of particle size and morphology, physicochemical stability over the time, extract encapsulation efficiency, release profile and biological activities (e.g., anti-inflammatory activity, collagenase inhibition, antioxidant activity). Small and well-defined polymeric nanoparticles and ethosomes were prepared. The highest encapsulation efficiency (76%) was found in PLGA nanoparticles. The same happened for the anti-inflammatory activity (60.7 ± 9.0%). On the other hand, ethosomes presented a very promising value of collagenase inhibition. At the end, this thesis validates and supports the scientific evidence of potential uses of S. nigra as a therapeutic agent, in the case of polymeric nanoparticles, or as cosmetic ingredient, in the case of ethosomes. However, further studies should be carried out, hopefully attracting interest from pharmaceutical and cosmetic industries.
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Basal and squamous cell skin cancers, collectively known as nonmelanoma skin cancers (NMSC), are the most common skin cancers. More than 1 million cases of NMSC are estimated to be diagnosed each year in the United States, and the incidence is rising rapidly. Although rarely metastatic, basal and squamous cell cancers can produce substantial local destruction, along with disfigurement. They are associated with substantial annual costs for treatment, despite their general good prognosis. The most significant environmental carcinogen for NMSC is sunlight. Most of these tumors develop on sun-exposed skin sites, commonly on the head and neck area. Important updates for 2010 include revision of the guidelines detailing dissection and treatment of squamous cell carcinoma on the head and neck.
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Consumption of green tea polyphenols (GTPs) in drinking water prevents photocarcinogenesis in mice; however, the molecular mechanisms underlying this effect have not been fully elucidated. Using IL-12p40 knockout (KO) mice and their wild-type counterparts and an established photocarcinogenesis protocol, we found that although administration of GTPs (0.2%, w/v) in drinking water significantly reduced UVB-induced tumor development in wild-type mice, this treatment had a nonsignificant effect in IL-12-KO mice. GTPs resulted in reduction in the levels of markers of inflammation (cyclooxygenase-2, prostaglandin E2, proliferating cell nuclear antigen, and cyclin D1) and proinflammatory cytokines (tumor necrosis factor-α, IL-6, and IL-1β) in chronically UVB-exposed skin and skin tumors of wild-type mice but less effective in IL-12p40-KO mice. UVB-induced DNA damage (cyclobutane pyrimidine dimers) was resolved rapidly in GTPs-treated wild-type mice than untreated wild-type mice and this resolution followed the same time course as the GTPs-induced reduction in the levels of inflammatory responses. This effect of GTPs was less pronounced in IL-12-KO mice. The above results were confirmed by treatment of IL-12-KO mice with murine recombinant IL-12 and treatment of wild-type mice with neutralizing anti-IL-12 antibody. To our knowledge, it is previously unreported that prevention of photocarcinogenesis by GTPs is mediated through IL-12-dependent DNA repair and a subsequent reduction in skin inflammation. JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article please go to http://network.nature.com/group/jidclub
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Exposing the skin of mice to UV radiation interferes with the induction of delayed and contact hypersensitivity immune responses initiated at nonirradiated sites. The identity of the molecular target in the skin for these immunosuppressive effects of UV radiation remains controversial. To test the hypothesis that DNA is the target for UV-induced systemic immunosuppression, we exposed C3H mice to UV radiation and then used liposomes to deliver a dimer-specific excision repair enzyme into the epidermis in situ. The application of T4 endonuclease V encapsulated in liposomes to UV-irradiated mouse skin decreased the number of cyclobutane pyrimidine dimers in the epidermis and prevented suppression of both delayed and contact hypersensitivity responses. Moreover, the formation of suppressor lymphoid cells was inhibited. Control, heat-inactivated endonuclease encapsulated in liposomes had no effect. These studies demonstrate that DNA is the major target of UV radiation in the generation of systemic immunosuppression and suggest that the primary molecular event mediating these types of immunosuppression by UV radiation is the formation of pyrimidine dimers. Furthermore, they illustrate that the delivery of lesion-specific DNA repair enzymes to living skin after UV irradiation is an effective tool for restoring immune function and suggest that this approach may be broadly applicable to preventing other alterations caused by DNA damage.
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UV exposure has been linked to skin cancer in humans by epidemiology and the rare genetic disease xeroderma pigmentosum. However, UV produces multiple photoproducts in DNA, and their relative contribution is uncertain. An enzyme which specifically repairs cyclobutane pyrimidine dimers in DNA, T4 endonuclease V, was encapsulated in liposomes for topical delivery into mouse and human skin. In both species, liposomes applied after UV exposure localized in the epidermis and stimulated the removal of cyclobutane pyrimidine dimers. UV-irradiated mice treated with these liposomes had a dose-dependent decrease in the incidence of squamous cell carcinoma compared to controls. The results demonstrate that unrepaired cyclobutane pyrimidine dimers in DNA are a direct cause of cancer in mammalian skin.
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We had reported previously that the outgrowth of melanoma is enhanced when melanoma cells are injected into UV-irradiated skin of syngeneic mice. To determine whether this effect was specific for melanomas, we compared the growth of 13 different tumor cell lines (3 melanomas, 6 fibrosarcomas, 2 undifferentiated skin tumors, a squamous cell carcinoma, and a spontaneous hepatocarcinoma) in UV-irradiated and nonirradiated syngeneic mice. C3H/HeN(MTV-) mice were exposed to 4.8 kJ/m2 UV-B (280-320 nm) radiation twice a week for 3 weeks; the tumor cells were injected into the UV-irradiated pinna 24 h after the final UV irradiation. The growth of all the melanomas and 4 of the fibrosarcomas was enhanced in UV-irradiated mice, indicating that the effect of UV radiation was not specific for melanomas or tumors of a particular etiology. Using an in vivo immunization and challenge assay, we found that the 7 tumors exhibiting enhanced development in UV-irradiated skin were highly immunogenic, whereas the remaining 6 tumors were not. This suggested that enhanced tumor outgrowth resulted from an immunosuppressive effect of the UV radiation. When tested further, we found that UV-B radiation had no effect on melanoma outgrowth in congenitally athymic mice, sublethally X-irradiated mice, or mice depleted of Thy1+ cells in vivo. These results indicate that immunological mechanisms play a role in the effect of UV radiation on the growth of murine melanomas.
Conference Paper
In recent years, the concept of cancer chemoprevention has matured greatly. Significant reversal or suppression of premalignancy in several sites by chemopreventive agents appears achievable. This article summarizes experimental data on chemopreventive effects of tea polyphenols in different tumor bioassay systems. Tea (Camellia sinensis) is cultivated in about 30 countries, and is the most widely consumed beverage in the world. Three main commercial tea varieties-green, black, and oolong-are usually consumed, but most experimental studies demonstrat ing the antimutagenic and anticarcinogenic effects of tea have been conducted with water extract of green tea, or a polyphenolic fraction isolated from green tea (GTP). The majority of these studies have been conducted in a mouse skin tumor model system where tea is fed either as water extract through drinking water, or as purified GTP. GTP has been shown to exhibit antimutagenic activity in vitro, and inhibit carcinogen-as well as UV-induced skin carcinogenesis in vivo. Tea consumption has also been shown to afford protection against chemical carcinogen-induced stomach, lung, esophagus, duodenum, pancreas, liver, breast, and colon carcinogenesis in specific bioassay models. Several epicatechin derivatives (polyphenols) present in green tea have been shown to possess anticarcinogenic activity; the most active is (-)-epigallocatechin-3-gallate, which is also the major constituent of GTP. The mechanisms of tea's broad cancer chemopreventive effects are not completely understood. Several theories have been put forward, including inhibition of UV-and tumor promoter-induced ornithine decarboxylase, cyclo-oxygenase, and lipoxygenase activities, antioxidant and free radical scavenging activity; enhancement of antioxidant (glutathione peroxidase, catalase and quinone reductase) and phase II (glutathione-S-transferase) enzyme activities; inhibition of lipid peroxidation, and anti-inflammatory activity. These properties of tea polyphenols make them effective chemopreventive agents against the initiation, promotion, and progression stages of multistage carcinogenesis. (C) 1998 Wiley-Liss, Inc.dagger
Article
Cancer, next only to heart diseases, is the second leading cause of deaths in the United States of America and many other nations in the world. The prognosis for a patient with metastatic carcinoma of the lung, colon, breast, or prostate (four of the most common and lethal forms of cancer, which together account for more than half of all deaths from cancer in the USA), remains dismal. Conventional therapeutic and surgical approaches have not been able to control the incidence of most of the cancer types. Therefore, there is an urgent need to develop mechanism-based approaches for the management of cancer. Chemoprevention via non-toxic agents could be one such approach. Many naturally occurring agents have shown cancer chemopreventive potential in a variety of bioassay systems and animal models, having relevance to human disease. It is appreciated that an effective and acceptable chemopreventive agent should have certain properties: (a), little or no toxic effects in normal and healthy cells; (b), high efficacy against multiple sites; (c), capability of oral consumption; (d), known mechanism of action; (e), low cost; and (f), acceptance by human population. Resveratrol is one such agent. A naturally occurring polyphenolie antioxidant compound present in grapes, berries, peanuts and red wine. In some bioassay systems resveratrol has been shown to afford protection against several cancer types. The mechanisms of resveratrol's broad cancer chemopreventive effects are not completely understood. In this review, we present the cancer chemopreventive effects of resveratrol in an organ-specific manner. The mechanists of the antiproliferative/cancer chemopreventive effects of resveratrol are also presented. We believe that continued efforts are needed, especially well-designed pre-clinical studies in the animal models that closely mimic/represent human disease, to establish the usefulness of resveratrol as cancer chemopreventive agent. This should be followed by human clinical trials in appropriate cancer types in suitable populations.
Article
Extensive documentation has validated the role of UV irradiation as a tumor initiator and promoter, inducing both squamous and basal cell carcinomas. Human epidermis is a tissue which undergoes active metabolism of arachidonic acid to prostaglandins which is regulated by the action of prostaglandin H synthase (also known as cyclooxygenase). One mechanism for the promotional activity of UV light may involve its ability to induce prostaglandin formation. Work in our laboratory has demonstrated that acute exposure of human keratinocytes to UVB irradiation results in increased production of prostaglandin E2 (PGE2). When cultured human keratinocytes were examined after irradiation with 30 mJ/cm 2 UVB in vitro, Western blot analysis showed a 6-fold increase in COX-2 protein which was evident at 6 h and peaked 24 h after irradiation. Furthermore, when human subjects were irradiated on sun-protected skin with up to four times their minimal erythema dosage (MED) and biopsied 24 h later, upregulation of COX-2 protein expression was observed via immunofluorescence microscopy. RNAase protection assays supported this observation, showing induction of COX-2 message which peaked at ~12 h following irradiation in vitro. Furthermore, human squamous cell carcinoma biopsies exhibited strongly enhanced staining for COX-2 protein via immunohistochemistry and Western analysis when compared to normal non-sun-exposed control skin. Together, these data demonstrate acute upregulation of COX-2 via UVB irradiation and suggest the need for further studies of COX-2 expression as a potential pharmacological target mediating human skin tumor development.
Article
Resveratrol, a phytoalexin found in grapes and other food products, was purified and shown to have cancer chemopreventive activity in assays representing three major stages of carcinogenesis. Resveratrol was found to act as an antioxidant and antimutagen and to induce phase II drug-metabolizing enzymes (anti-initiation activity); it mediated anti-inflammatory effects and inhibited cyclooxygenase and hydroperoxidase functions (antipromotion activity); and it induced human promyelocytic leukemia cell differentiation (antiprogression activity). In addition, it inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. These data suggest that resveratrol, a common constituent of the human diet, merits investigation as a potential cancer chemopreventive agent in humans.
Article
Skin cancer is the most common malignancy arising inthe posttransplantation setting. Multiple factors contribute to the high risk for cutaneous carcinoma in immunosuppressed organ-transplant recipients. We review the phenomenon of skin cancer in solid-organ transplant recipients and further delineate the problem in the context of liver transplantation. Skin cancer is a significant medical and surgical problem for organ-transplant recipients. With prolonged allograft function and patient survival, the majority of solid-organ transplant recipients will eventually develop skin cancer. Although squamous cell carcinoma is the most common cutaneous malignancy in this population, basal cell carcinoma, melanoma, and Kaposi's sarcoma, as well as uncommon skin malignancies, may occur. Highly susceptible patients may develop hundreds of squamous cell carcinomas, which may be life threatening. Management strategies focus on regular full-skin and nodal examination, aggressive treatment of established malignancies, and prophylactic measures to reduce the risk for additional photodamage and malignant transformation. Skin cancer is a substantial cause of morbidity and even mortality among solid-organ transplant recipients. As a byproduct of immunosuppression, liver transplant recipients experience a high incidence of skin cancer and should be educated and managed accordingly.
Article
• There is evidence suggesting a role of eicosanoids in the growth of certain tumors. In this study, tissue samples were collected from basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) of the skin. Both BCCs and SCCs contained more prostaglandin E2 and F2α (PGE2 and PGF2α) than normal epidermis. In vitro incubation of tumor samples with arachidonic acid also resulted in PGE2 and PGF2α formation. Basal cell carcinomas exhibiting a histologically aggressive growth pattern contained higher levels of prostaglandins than those with a nonaggressive growth pattern, both in vivo and after in vitro incubation. Lipoxygenase products (12- and 15-hydroxyeicosatetraenoic acid) were present in smaller amounts than cyclo-oxygenase products (PGE2 and PGF2α) in vivo. Compared with normal epidermis, SCCs and, particularly, BCCs produced smaller amounts of 12-hydroxyeicosatetraenoic acid during in vitro incubation with arachidonic acid. The levels of lipoxygenase products were not related to the tumor growth pattern. These results indicate that excessive prostaglandin levels in BCCs may be associated with an aggressive growth pattern. (Arch Dermatol 1986;122:407-412)
Article
This 392-page text is outstanding. Goepfert, Weber, and Miller are exceptional and distinguished clinicians and scholars. They have successfully edited and delivered a comprehensive textbook to serve as a resource for those physicians caring for patients afflicted with complex cutaneous basal cell and squamous cell carcinoma. This textbook emphasizes the multidisciplinary management of advanced basal cell and squamous cell carcinoma of the head and neck. The first 65 pages deal with epidemiology, pathology, molecular biology, immunobiology, and mechanisms of invasion and metastasis. The remaining majority of the text focuses on comprehensive clinical management of patients with advanced nonmelanoma skin cancer. Physicians treating nonmelanoma skin cancer will benefit from an understanding of management options and guidelines for the more advanced and complicated cases of nonmelanoma skin cancer. Several chapters are considerably interesting and will add to the dermatologist's library of standard cutaneous oncology and surgery texts. Specific examples of excellent and
Article
We reported the inhibitory effects of genistein, an inhibitor of tyrosine protein kinase (TPK), on ultraviolet B (UVB)-induced expression of c-fos and c-jun in SENCAR mouse skin. UVB irradiation substantially increased transcript levels of c-fos and c-jun mRNA in mouse skin. Topical application of genistein 60 min before UVB radiation reduced c-fos and c-jun expression in the mouse skin in dose-dependent manner. Inhibition was more pronounced in skin exposed to the low dose (5 kJ/m 2 ) than to the high dose (15 kJ/m 2 ) of UVB radiation. In addition, genistein exhibited more inhibition of c-fos than that of c-jun. Post-application of genistein after UVB exposure down-regulated the expressions of c-fos and c-jun, but to a lesser extent compared with pre-application. A431 human epidermoid carcinoma cells, which excessively express epidermal growth factor receptors (EGF-R), were used to investigate the possible mechanism of genistein's action. The results showed that genistein down-regulated the UVB-mediated phosphorylation of TPK-dependent EGF-R in a dose-dependent manner. We concluded that inhibition of UVB-induced c-fos and c-jun expression in mouse skin by genistein may, at least in part, result from the inhibition of TPK activities and down-regulation of EGF-R phosphorylation. Suppression of UVB-induced proto-oncogene expression in mouse skin suggests that genistein may serve as a potential preventative agent against photodamage and photocarcinogenesis.
Article
Nonmelanoma skin cancer is the most common cancer among humans and solar UV radiation, particularly its UVB component (290–320 nm), is its major cause. One way to reduce the occurrence of the cancer is via the use of substances (often antioxidants) termed “photochemopreventive agents”. Resveratrol (trans-3,4′,5-trihydroxystilbene), a phytoalexin found in grapes, nuts, fruits, and red wine, is a potent antioxidant with strong anti-inflammatory and antiproliferative properties. This study was designed to examine whether resveratrol possesses the potential to ameliorate the damages caused by short-term UVB exposure to mouse skin. Single topical application of resveratrol (25 μmol/0.2 ml acetone per mouse) to SKH-1 hairless mice was found to result in significant inhibition of UVB (180 mJ/cm2)-mediated increase in bifold skin thickness and skin edema. The resveratrol treatment to mouse skin was also found to result in significant inhibition of UVB-mediated induction of cyclooxygenase and ornithine decarboxylase (ODC) enzyme activities and protein expression of ODC, which are well-established markers for tumor promotion. We also observed that resveratrol inhibits UVB-mediated increased level of lipid peroxidation, a marker of oxidative stress. Taken together, our results suggest that resveratrol may afford substantial protection against the damages caused by UVB exposure, and these protective effects may be mediated via its antioxidant properties.
Article
Introduction The increased incidence of skin cancers is due to modifications of our behavior toward solar exposure. Photocarcinogenesis represents the sum of complex and intricated events that lead to the occurrence of skin cancers. Current knowledge and key points In epidermic cells UV light induces lesions of DNA that lead to modifications in oncogene and tumor suppressor gene expression. UV-induced immunosuppression is also important for tumoral promotion. UV exposure decreases the number of Langerhans cells in the epidermis and modifïes their antigen-presenting cell capacity. Numerous experimental data obtained in animal models clearly indicate the existence of a relationship between UV-induced immune suppression and skin cancers. In humans, growing evidence suggests that skin cancers and photoimmunosuppression are linked. Future prospects and projects Better knowledge of mechanisms involved in UV-induced immune suppression is essential for developing new strategies aimed at photoprotection and cancer prevention.
Article
ABSTRACT Cyclooxygenase (COX)-1- and COX-2-deficient mice have unique physiological differences that have allowed investigation into the individual biological roles of the COX isoforms. In the following, the phenotypes of the two COX knockout mice are summarized, and recent studies to investigate the effects of COX deficiency on inflammatory responses and cancer susceptibility are discussed. The data suggest that both isoforms have important roles in the maintenance of physiological homeostasis and that such designations as housekeeping and/or response gene may not be entirely accurate. Furthermore, data from COX-deficient mice indicate that both isoforms can contribute to the inflammatory response and that both isoforms have significant roles in carcino-genesis.
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Nonmelanoma skin cancer is the most frequently diagnosed malignancy in the United States, and multiple exposures to solar ultraviolet (UV) radiation (particularly its UV-B component, 290–320 nm) is its major cause. “Chemoprevention”by naturally occurring agents is being appreciated as a newer dimension in the management of neoplasia including skin cancer. We recently demonstrated that resveratrol (trans-3,5,4-trihydroxystilbene), an antioxidant found in grapes, red wines and a variety of nuts and berries, imparts protection from acute UV-B–mediated cutaneous damages in SKH-1 hairless mice. Understanding the mechanism of resveratrol-mediated protection of UV responses is important. We earlier demonstrated that resveratrol imparts chemopreventive effects against multiple UV-exposure–mediated modulations in (1) cki-cyclin-cdk network and (2) mitogen activated protein kinase (MAPK)-pathway. This study was conducted to assess the involvement of inhibitor of apoptosis protein family protein Survivin during resveratrol-mediated protection from multiple exposures of UV-B (180 mJ/cm2; on alternate days; for a total of seven exposures) radiations in the SKH-1 hairless mouse skin. Our data demonstrated that topical pretreatment of resveratrol (10 μmol in 200 μL acetone/mouse) resulted in significant inhibition of UV-B exposure-mediated increases in (1) cellular proliferations (Ki-67 immunostaining), (2) protein levels of epidermal cyclooxygenase-2 and ornithine decarboxylase, established markers of tumor promotion, (3) protein and messenger RNA levels of Survivin, and (4) phosphorylation of survivin in the skin of SKH-1 hairless mouse. Resveratrol pretreatment also resulted in (1) reversal of UV-B–mediated decrease of Smac/DIABLO and (2) enhancement of UV-B–mediated induction of apoptosis, in mouse skin. Taken together, our study suggested that resveratrol imparts chemopreventive effects against UV-B exposure–mediated damages in SKH-1 hairless mouse skin via inhibiting Survivin and the associated events.
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Although different theories have been proposed to explain the aging process, it is generally agreed that there is a correlation between aging and the accumulation of oxidatively damaged proteins, lipids, and nucleic acids. Oxidatively modified proteins have been shown to increase as a function of age. Studies reveal an age-related increase in the level of protein carbonyl content, oxidized methionine, protein hydrophobicity, and cross-linked and glycated proteins as well as the accumulation of less active enzymes that are more susceptible to heat inactivation and proteolytic degredation. Factors that decelerate protein oxidation also increase the life span of animals and vice versa. Furthermore, a number of age-related diseases have been shown to be associated with elevated levels of oxidatively modified proteins. The chemistry of reactive oxygen species-mediated protein modification will be discussed. The accumulation of oxidatively modified proteins may reflect deficiencies in one or more parameters of a complex function that maintains a delicate balance between the presence of a multiplicity of prooxidants, antioxidants, and repair, replacement, or elimination of biologically damaged proteins.
Chapter
The major stages of chemical carcinogenesis have been deduced over the past ∼50 years, primarily from animal model studies (and particularly from studies using the mouse skin model); these stages are termed initiation, promotion, and progression. Tumor initiation begins when DNA in a cell or population of target cells is damaged by exposure to exogenous or endogenous carcinogens leading to mutations in critical target genes. The responsiveness of initiated cells to their microenvironment gives them a growth advantage relative to normal cells under certain conditions. In the classic two-stage chemical carcinogenesis system in the mouse skin, a low dose of a carcinogen such as 7,12-dimethylbenz(a)anthracene induces a mutation in Hras1 that does not give rise to tumors over the lifespan of the mouse unless a tumor promoter, such as TPA, is repeatedly applied. The tumor promotion stage is characterized by selective clonal expansion of the initiated cells, a result of the altered expression of genes whose products are associated with hyperproliferation, tissue remodeling, and inflammation. During tumor progression, preneoplastic cells undergo malignant transformation through a process of selection that is facilitated by progressive genomic instability and altered gene expression. While the processes involved in each stage of experimental chemical carcinogenesis also appear to be involved in human carcinogenesis, the temporal nature of initiation, promotion, and progression events is more complex. In addition, multiple mutational events are involved in the formation of human tumors. Genetic background and nutritional status can dramatically affect susceptibility to a carcinogenic exposure in both experimental animals and humans. An understanding of the multistage nature of carcinogenesis has led to the discovery of mechanism-based inhibitors that target events associated with specific stages. Further study of the cellular, biochemical, and molecular mechanisms associated carcinogenesis induced by chemicals and other types of carcinogens will lead to identification of effective strategies for cancer prevention.
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Ultraviolet (UV) irradiation plays a pivotal role in human skin carcinongenesis. Preclinically, systemically and topically applied green tea extract (GTE) has shown reduction of UV-induced (i) erythema, (ii) DNA damage, (iii) formation of radical oxygen species and (iv) downregulation of numerous factors related to apoptosis, inflammation, differentiation and carcinogenesis. In humans, topical GTE has so far only been tested in limited studies, with usually very high GTE concentrations and over short periods of time. Both chemical stability of GTE and staining properties of highly concentrated green tea polyphenols limit the usability of highly concentrated green tea extracts in cosmetic products. The present study tested the utility of stabilized low-dose GTE as photochemopreventive agents under everyday conditions. We irradiated with up to 100 mJ/cm(2) of UVB light skin patches which were pretreated with either OM24-containing lotion or a placebo lotion. Biopsies were taken from both irradiated and un-irradiated skin for both immunohistochemistry and DNA microarray analysis. We found that while OM24 treatment did not significantly affect UV-induced erythema and thymidine dimer formation, OM24 treatment significantly reduced UV-induced p53 expression in keratinocytes. We also found that OM24 treatment significantly reduced the number of apoptotic keratinocytes (sunburn cells and TUNEL-positive cells). Carefully controlled DNA microarray analyses showed that OM24 treatment does not induce off-target changes in gene expression, reducing the likelihood of unwanted side-effects. Topical GTE (OM24) reduces UVB-mediated epithelial damage already at low, cosmetically usable concentrations, without tachyphylaxis over 5 weeks, suggesting GTE as suitable everyday photochemopreventive agents.
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We previously demonstrated that ultraviolet (UV) light (254 nm) induced the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA via a singlet oxygen mechanism. In the present paper, we provide novel findings that DNA structure and base composition significantly affect the yield of 8-OHdG by UV radiation. Unlike ionizing radiation that induces 8-OHdG both in free 2'-deoxyguanosine (dG) and in DNA, UV light induced 8-OHdG formation in intact DNA and polydG.dC, but not in dG. When thermally denatured DNA was irradiated with UV light, the yield of 8-OHdG was reduced by more than 80% compared to intact DNA. Oxygenation of the denatured DNA solution did not restore the yield of UV-induced 8-OHdG. Irradiation of DNA with different AT/GC ratios showed that the yield of UV-induced 8-OHdG varied in proportion to the AT content, suggesting that AT base pairs in DNA enhance generation of the oxidizing species and subsequent oxidation of dG. The natural antioxidants genistein, estradiol, protocatechuic acid (PCA), and oleanolic acid (OA) were investigated for their inhibition of UV-induced 8-OHdG. Genistein and estradiol, that intercalate into DNA as shown by a computer modeling, significantly quenched UV-induced 8-OHdG, whereas PCA and OA did not fit into DNA and exhibited weak or no effect. These results suggest that the intercalation of genistein and estradiol into DNA may alter the DNA structural integrity, interrupt the production of oxidizing species, and subsequently reduce the formation of 8-OHdG by UV radiation.
Article
This study aimed to investigate whether the sunscreen-containing 2-5% green tea extracts (GTEs) protect ultraviolet irradiation (UVR)-induced photoaging and photoimmunosuppression. Twenty volunteers were exposed to repetitive solar-simulated UVR (ssUVR) on the upper back at a dosage of 1.5 minimal erythema doses (MED) per day for four consecutive days. Thirty minutes before each UVR and 6, 24, and 48 h after the last UV exposure, the products containing vehicle, and 2-5% GTEs were applied onto five sites on the dorsal skin, respectively. The skin biopsies were obtained 72 h after the last UVR. The thickness of the stratum corneum and epidermis was measured under the microscope and the expression of cytokeratins (CK)-5/6, CK16, metalloproteinases (MMP)-2, MMP-9, and the CD1a(+) Langerhans cells (LCs) were determined using immunohistochemistry. Our results showed that UVR substantially induced cutaneous erythema, thickening of the epidermis, overexpression of CK5/6, CK16, MMP-2, MMP-9, and depletion of CD1a(+) LCs. The sunscreens containing different concentrations of GTEs conferred significant protection against the photoaging and photoimmunology-related biological events. Interestingly, the protective effects were not parallel to the concentrations of GTEs, with 2% and 3% GTEs showing the most efficacious photoprotection. GTEs-containing sunscreens have potential photoprotective effects on UVR-induced photoaging and photoimmunosuppression.
Article
Tea polyphenols have been found to exert beneficial effects on the skin via their antioxidant properties. We sought to determine whether topical application of green tea or white tea extracts would prevent simulated solar radiation-induced oxidative damages to DNA and Langerhans cells that may lead to immune suppression and carcinogenesis. Skin samples were analysed from volunteers or skin explants treated with white tea or green tea after UV irradiation. In another group of patients, the in vivo immune protective effects of green and white tea were evaluated using contact hypersensitivity to dinitrochlorobenzene. Topical application of green and white tea offered protection against detrimental effects of UV on cutaneous immunity. Such protection is not because of direct UV absorption or sunscreen effects as both products showed a sun protection factor of 1. There was no significant difference in the levels of protection afforded by the two agents. Hence, both green tea and white tea are potential photoprotective agents that may be used in conjunction with established methods of sun protection.
Article
Excessive exposure to UV radiation causes acute adverse effects like sunburn and photosensitivity reactions and is involved in the induction and development of skin cancer. It has been reported that antioxidants have photoprotective effects against solar UV radiation. We investigated the effect of oral epigallocatechin gallate (EGCG), a powerful antioxidant in green tea, on the minimal erythema dose (MED) and UV-induced skin damage. Female HWY/Slc hairless rats were fed the normal diet supplemented with 1,500 ppm EGCG for 8 weeks; then, the MED was determined and visual scores and transepidermal water loss were assessed to evaluate the severity of UV-induced skin damage. At week 8 of the study, the use of dietary EGCG significantly increased MED. UV-radiation-induced sunburn severity and alterations in epidermal barrier function were also attenuated by the supplementation of EGCG. Regular intake of EGCG strengthens the skin's tolerance by increasing MED and thus prevents UV-induced perturbation of epidermal barrier function and skin damage. These results suggest that EGCG is a potent candidate for systemic photoprotection.
Article
The oligomeric proanthocyanidins (OPCs) from grape seeds are expected to be novel and potent anti-oxidants that more effectively protect skin cells against oxidative stress. UV-induced oxidative stress is considered to promote melanogenesis and serious skin damage. However, the effect of OPCs on UV-induced melanogenesis is still unknown. To investigate the role of OPCs on melanogenesis of human melanocytes with UV exposure, we evaluated the effects of melanogenesis, cellular cycle, intracellular reactive oxidative species (ROS) level and protein level of melanogenic enzyme in cultured human melanocytes following UV-irradiation by OPCs. After treatment with different doses of OPCs or L-ascorbic acid, normal human melanocytes (NHM) were irradiated by 15 mJ/cm2 UV light. Then, cellular melanin content, activity of tyrosinase were examined. Moreover, the protein analysis of tyrosinase, tyrosinase related protein 1 (TRP1), and tyrosinase related protein 2 (TRP2) were observed by Western blotting. Levels of UV-induced ROS in melanocytes and the responses of cell cycle were also examined by immunofluorescence techniques. This study demonstrated that OPCs, significantly inhibited the cell dead induced by UV irradiation in a dose-dependent manner and OPCs alone, has no effects on melanogenesis of NHM, however, it significantly inhibited UV-induced melanogenesis in a dose-dependent manner. The UV-induced intracellular ROS enhancement was also prevented by addition of OPCs in a dose-dependent manner. Meanwhile, OPCs also inhibited the extent of G1 arrest that was induced by UV exposure. OPCs can decrease the protein level of tyrosinase, TRP1 and TRP2 in UV-irradiated NHM. Thus, OPCs have potential effects of photoprotection on human melanocytes by improving cell viability, scavenging intracellular ROS, adjusting cell cycle and inhibiting protein expression of melanogenic enzymes.
Article
A collaborative study including centres in the United Kingdom, Australia, and New Zealand was instituted in 1970 to determine the incidence of cancer in patients treated for at least three months with azathioprine, cyclophosphamide, or chlorambucil. Follow-up of 3823 renal transplant recipients showed an almost 60-fold increase of non-Hodgkin's lymphoma together with an excess of squamous-cell skin cancer and mesenchymal tumours. A series of 1349 patients without transplants showed an excess of the same tumours, though to a less extent. These preliminary findings provide no clear evidence that immunosuppressive drugs produce the increased risk of most of the common cancers that might be expected from the simplest interpretation of impaired "immunosurveillance."