RESUMO
Humans in modern industrial and postindustrial societies face sustained challenges from environmental pollutants, which can trigger tissue damage from xenotoxic stress through different mechanisms. Thus, the identification and characterization of compounds capable of conferring antioxidant effects and protection against these xenotoxins are warranted. Here, we report that the natural extract of Polypodium leucotomos named Fernblock®, known to reduce aging and oxidative stress induced by solar radiations, upregulates the NRF2 transcription factor and its downstream antioxidant targets, and this correlates with its ability to reduce inflammation, melanogenesis, and general cell damage in cultured keratinocytes upon exposure to an experimental model of fine pollutant particles (PM2.5). Our results provide evidence for a specific molecular mechanism underpinning the protective activity of Fernblock® against environmental pollutants and potentially other sources of oxidative stress and damage-induced aging.
Assuntos
Antioxidantes/uso terapêutico , Queratinócitos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Antioxidantes/farmacologia , Humanos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Regulação para CimaRESUMO
Skin is being increasingly exposed to artificial blue light due to the extensive use of electronic devices. This, together with recent observations reporting that blue light-also known as high-energy visible light-can exert cytotoxic effects associated with oxidative stress and promote hyperpigmentation, has sparked interest in blue light and its potential harmful effects on skin. The photoprotective properties of new extracts of different botanicals with antioxidant activity are therefore being studied. Deschampsia antarctica (Edafence®, EDA), a natural aqueous extract, has shown keratinocyte and fibroblast cell protection effects against ultraviolet radiation and dioxin toxicity. In this regard, we studied the protective capacity of EDA against the deleterious effects of artificial blue light irradiation in human dermal fibroblasts (HDF) and melanocytes. We analyzed the impact of EDA on viability, cell morphology, oxidative stress, melanogenic signaling pathway activation and hyperpigmentation in HDF and melanocytes subjected to artificial blue light irradiation. Our results show that EDA protects against cell damage caused by artificial blue light, decreasing oxidative stress, melanogenic signaling pathway activation and hyperpigmentation caused by blue light irradiation. All these findings suggest that EDA might help prevent skin damage produced by artificial blue light exposure from screen of electronic devices.
Assuntos
Luz/efeitos adversos , Extratos Vegetais/farmacologia , Poaceae/química , Substâncias Protetoras/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Dispositivos Eletrônicos Vestíveis/efeitos adversos , Sobrevivência Celular , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/efeitos da radiação , Humanos , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Estresse Oxidativo , Espécies Reativas de Oxigênio , Pele/citologia , Pele/efeitos da radiação , Envelhecimento da Pele/patologiaRESUMO
Solar radiation in the ultraviolet (UV), visible (VIS), and infrared (IR) ranges produces different biological effects in humans. Most of these, particularly those derived from ultraviolet radiation (UVR) are harmful to the skin, and include cutaneous aging and increased risk of cutaneous diseases, particularly skin cancer. Pharmacological photoprotection is mostly topical, but it can also be systemic. Oral photoprotectives constitute a new generation of drugs to combat the deleterious effects of solar radiation. Among these, an extract of Polypodium leucotomos (PL/Fernblock®, IFC Group, Spain) contains a high content of phenolic compounds that endow it with antioxidant activity. PL can administered orally or topically and is completely safe. PL complements and enhances endogenous antioxidant systems by neutralizing superoxide anions, hydroxyl radicals, and lipoperoxides. In addition to its antioxidant activity, PL also improves DNA repair and modulates immune and inflammatory responses. These activities are likely due to its ability to inhibit the generation and release of reactive oxygen species (ROS) by UVR, VIS, and IR radiation. PL also prevents direct DNA damage by accelerating the removal of induced photoproducts and decreasing UV-induced mutations. Oral PL increases the expression of active p53, decreases cell proliferation, and inhibits UV-induced COX-2 enzyme levels. PL has been used to treat skin diseases such as photodermatoses and pigmentary disorders and recently as a complement of photodynamic phototherapy in actinic keratoses. The photoprotective capability of PL has been proven in a multitude of in vitro and in vivo studies, which include animal models and clinical trials with human subjects. Based on this evidence, PL is a new generation photoprotector with antioxidant and anti-inflammatory properties that also protects DNA integrity and enhances the immune response.
Assuntos
Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Polypodium/química , Substâncias Protetoras/farmacologia , Administração Oral , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Dano ao DNA , Humanos , Radical Hidroxila/antagonistas & inibidores , Radical Hidroxila/metabolismo , Raios Infravermelhos , Peróxidos Lipídicos/antagonistas & inibidores , Peróxidos Lipídicos/metabolismo , Camundongos , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos , Processos Fotoquímicos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/química , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Pele/efeitos dos fármacos , Superóxidos/antagonistas & inibidores , Superóxidos/metabolismo , Raios Ultravioleta , Água/químicaRESUMO
Sun overexposure leads to higher risk of photoaging and skin cancer. The contribution of infrared (IR) and visible light (VIS) radiation is currently being taken into account in their pathogenesis. Erythema, hyperpigmentation, genotoxicity or the increase of matrix metalloproteinases (MMPs) expression are some of the effects induced by these types of radiation. Extracts of various botanicals endowed with antioxidant activity are emerging as new photoprotective compounds. A natural extract from Polypodium leucotomos (Fernblock®, FB) has antioxidant and photoprotective properties and exhibits a strong anti-aging effect. In this study, we evaluated the protective capacity of FB against the detrimental effects of infrared A (IRA) and VIS radiation in human dermal fibroblasts. We analyzed the effects of FB on the morphology, viability, cell cycle and expression of extracellular matrix components of fibroblasts subjected to VIS and IRA. Our results indicate that FB prevents cell damage caused by VIS and IRA. Moreover, it reduces the increase in MMP-1 and cathepsin K expression induced by both VIS and IRA radiation, and curbs alterations in fibrillin 1, fibrillin 2 and elastin expression. All these findings support FB as a feasible approach to prevent or treat skin damage caused by IRA or VIS exposure.
Assuntos
Derme/lesões , Derme/metabolismo , Fibroblastos/metabolismo , Raios Infravermelhos/efeitos adversos , Extratos Vegetais/farmacologia , Envelhecimento da Pele/efeitos dos fármacos , Neoplasias Cutâneas/prevenção & controle , Derme/patologia , Fibroblastos/patologia , Humanos , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
Electromagnetic radiation in the ultraviolet, visible, and infrared ranges produces biologic effects in humans. Where some of these effects are beneficial, others are harmful to the skin, particularly those stemming from ultraviolet radiation (UVR). Pharmacological photoprotection can be topical or systemic. Systemic photoprotection is often administered orally, complementing topical protection. New and classic oral agents (e.g., essential micronutrients as vitamins, minerals, polyphenols, carotenoids) are endowed with photoprotective and anti-photocarcinogenic properties. These substances bear the potential to increase systemic protection against the effects of electromagnetic radiation in the UV, visible, and infrared ranges. Protective mechanisms vary and include anti-oxidant, anti-inflammatory, and immunomodulatory effects. As such, they provide protection against UVR and prevent photo-induced carcinogenesis and aging. In this review, we present state of the art approaches regarding the photoprotective effects of vitamins and vitamin derivatives, dietary botanical, and non-botanical agents. A growing body of data supports the beneficial effects of oral photoprotection on the health of the skin. More studies will likely confirm and expand the positive impact of oral dietary botanicals as complementary measures for photoprotection.
Assuntos
Antioxidantes/uso terapêutico , Neoplasias/prevenção & controle , Antioxidantes/química , Antioxidantes/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Suplementos Nutricionais , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Estresse Oxidativo/efeitos dos fármacosRESUMO
The Antarctic plant Deschampsia antarctica (DA) is able to survive in extreme conditions thanks to its special mechanism of protection against environmental aggressions. In this work, we investigated whether an aqueous extract of the plant (EDA) retains some of its defensive properties and is able to protect our skin against common external oxidants. We evaluated EDA over young human fibroblasts and exposed to H2O2, and we measured cell proliferation, viability, and senescence-associated ß-galactosidase (SA-ß-Gal). We also tested the expression of several senescence-associated proteins including sirtuin1, lamin A/C, the replicative protein PCNA, and the redox protein thioredoxin 2. We found that EDA promoted per se cell proliferation and viability and increased the expression of anti-senescence-related markers. Then, we selected a dose of H2O2 as an inductor of senescence in human fibroblasts, and we found that an EDA treatment 24 h prior H2O2 exposure increased fibroblast proliferation. EDA significantly inhibited the increase in SA-ß-Gal levels induced by H2O2 and promoted the expression of sirtuin 1 and lamin A/C proteins. Altogether, these results suggest that EDA protects human fibroblasts from cellular senescence induced by H2O2, pointing to this compound as a potential therapeutic agent to treat or prevent skin senescence.
Assuntos
Senescência Celular/efeitos dos fármacos , Fibroblastos/metabolismo , Peróxido de Hidrogênio/farmacologia , Extratos Vegetais/farmacologia , Envelhecimento , Proliferação de Células , HumanosRESUMO
Healthier life styles include increased outdoors time practicing sports and walking. This means increased exposure to the sun, leading to higher risk of sunburn, photoaging and skin cancer. In addition to topical barrier products, oral supplementations of various botanicals endowed with antioxidant activity are emerging as novel method of photoprotection. Polypodium leucotomos extract (PL, commercial name Fernblock(®), IFC Group, Spain) is a powerful antioxidant due to its high content of phenolic compounds. PL is administered orally, with proven safety, and it can also be used topically. Its mechanisms include inhibition of the generation and release of reactive oxygen species (ROS) by ultraviolet (UV) light. It also prevents UV- and ROS-induced DNA damage with inhibition of AP1 and NF-κB and protection of natural antioxidant enzyme systems. At the cellular level, PL decreases cellular apoptosis and necrosis mediated UV and inhibits abnormal extracellular matrix remodeling. PL reduces inflammation, prevents immunosuppression, activates tumor suppressor p53 and inhibits UV-induced cyclooxygenase-2 (COX-2) enzyme expression. In agreement with increased p53 activity, PL decreased UV radiation-induced cell proliferation. PL also prevents common deletions mitochondrial DNA damage induced by UVA, and MMP-1 expression induced Visible Light and Infrared Radiation. These cellular and molecular effects are reflected in inhibitions of carcinogenesis and photoaging.
Assuntos
Extratos Vegetais/farmacologia , Polypodium/química , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Animais , Humanos , Luz/efeitos adversos , Extratos Vegetais/uso terapêutico , Pele/metabolismo , Dermatopatias/metabolismo , Dermatopatias/prevenção & controle , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/prevenção & controleRESUMO
The role of reactive oxygen species (ROS) in the regulation of hair follicle (HF) cycle and skin homeostasis is poorly characterized. ROS have been traditionally linked to human disease and aging, but recent findings suggest that they can also have beneficial physiological functions in vivo in mammals. To test this hypothesis, we transiently switched on in situ ROS production in mouse skin. This process activated cell proliferation in the tissue and, interestingly, in the bulge region of the HF, a major reservoir of epidermal stem cells, promoting hair growth, as well as stimulating tissue repair after severe burn injury. We further show that these effects were associated with a transient Src kinase phosphorylation at Tyr416 and with a strong transcriptional activation of the prolactin family 2 subfamily c of growth factors. Our results point to potentially relevant modes of skin homeostasis regulation and demonstrate that a local and transient ROS production can regulate stem cell and tissue function in the whole organism.
Assuntos
Queimaduras/patologia , Proliferação de Células/fisiologia , Fototerapia , Espécies Reativas de Oxigênio/metabolismo , Nicho de Células-Tronco/fisiologia , Cicatrização/fisiologia , Animais , Queimaduras/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Feminino , Cabelo/crescimento & desenvolvimento , Folículo Piloso/metabolismo , Humanos , Imuno-Histoquímica , Queratinócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Distribuição AleatóriaRESUMO
A single dose of ultraviolet radiation (UVR) induces significant changes in blood and skin of hairless mice. Oral administration of a hydrophilic extract of the fern Polypodium leucotomos (PL, 300 mg/kg during 5 days before UVR and for two additional days after irradiation) modulates some of the effects of UVR. Most significantly, PL administration reduced the number of proliferating cells by 13%, increased the number of p53(+) cells by 63%, enhanced the antioxidant plasma capacity (ORAC) by 30% and reinforced the network of dermal elastic fibres. Western blot analysis of skin antioxidant-related enzymes failed to demonstrate significant changes caused by PL. Thus, the beneficial effect of PL likely owes to its antioxidant and anti-ROS properties rather than its modulation of the expression of endogenous antioxidant systems. These data provide mechanistic clues for its efficacy as a systemic photoprotective agent with antioxidant and anti-photo-ageing properties.
Assuntos
Antioxidantes/metabolismo , Proliferação de Células/efeitos dos fármacos , Epiderme/metabolismo , Epiderme/patologia , Extratos Vegetais/farmacologia , Polypodium , Proteína Supressora de Tumor p53/metabolismo , Raios Ultravioleta/efeitos adversos , Administração Oral , Animais , Relação Dose-Resposta à Radiação , Tecido Elástico/metabolismo , Epiderme/efeitos dos fármacos , Feminino , Camundongos , Camundongos Pelados , Modelos Animais , Extratos Vegetais/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
Many phytochemicals are endowed with photoprotective properties, i.e., the capability to prevent the harmful effects of excessive exposure to ultraviolet (UV) light. These effects include photoaging and skin cancer, and immunosuppression. Photoprotection is endowed through two major modes of action: UV absorption or reflection/scattering; and tissue repair post-exposure. We and others have uncovered the photoprotective properties of an extract of the fern Polypodium leucotomos (commercial name Fernblock). Fernblock is an all-natural antioxidant extract, administered both topically (on the skin) or orally. It inhibits generation of reactive oxygen species (ROS) production induced by UV including superoxide anion. It also prevents damage to the DNA, inhibits UV-induced AP1 and NF-κB, and protects endogenous skin natural antioxidant systems, i.e., CAT, GSH, and GSSR. Its photoprotective effects at a cellular level include a marked decrease of UV-mediated cellular apoptosis and necrosis and a profound inhibition of extracellular matrix remodeling. These molecular and cellular effects translate into long-term inhibition of photoaging and carcinogenesis that, together with its lack of toxicity, postulate its use as a novel-generation photoprotective nutriceutical of phytochemical origin.