Plant extracts and natural compounds used against UVB-induced photoaging

Por Administrator
en 31 Julio 2017

 

In an era that has been witnessing a significant increase in life expectancy and consequent growth of the elderly population, knowledge of physiological changes and diseases most frequently observed in older skin is particularly important (Kim et al. 2013). Moreover, the appearance of elderly skin and the increasing demand for therapeutic interventions to minimize aging manifestations has led to a renewed interest in this matter by researchers, pharmaceutical and cosmetic industries (Draelos 2000). The market for natural cosmetic products is one of the fastest growing in the world and according to a recent survey, the global demand for these personal care products is expected to increase around 9.6% until 2018 (source: Transparent Market Research, http://www.transparencymarketresearch.com/organic-personal-care-products.html). The fields of skincare research and pharmacological characterization of natural compounds are evolving together with the demand of the market (Tundis et al. 2015).

 

Natural compounds are used for dermatologic purposes both as oral dietary supplements as well as in topical cosmetic formulations (Allemann and Baumann 2009). The vast array of techniques currently available to investigate skin responsivity to multiple stimuli has brought about a new era in cosmetic and dermocosmetic development based on a robust understanding of skin physiology and its varied responses to commonly encountered environmental insults (Dreno et al. 2014). The importance of cosmetic research is not only related to improving the skin overall appearance during aging, but also aims to offer better quality of life acting through prevention and treatment of skin disorders related to the aging process (Kraft and Lynde 2005). Several active ingredients have been identified as regulatory elements of skin homeostasis, with potential cosmetic and/or dermatological applications (Gaspar et al. 2008; Watson et al. 2009; Kanlayavattanakul and Lourith 2010; Anunciato and da Rocha Filho 2012); however, the effectiveness of many formulations has yet to be confirmed. Moreover, considering the diversity of plants and natural compounds available, this field of study has large potential for growth. Given this fact, a discussion of all the currently available literature related to natural compounds and plant extracts used in dermatology would exceed the scope of this manuscript. In this article, we will provide a comprehensive review of the most relevant publications related to the use of plant extracts and natural compounds to prevent or ameliorate the effects of UVB irradiation on the skin.

Plant extracts used against UVB-induced photodamage

In this review, the most important and recent studies concerning plant species with anti-photoaging activities are described along with information on pharmacological effects of the relevant extracts against molecular processes driving skin aging in cellular and animal models. The scientific and common names, part of the plants used in the studies, identified bioactives as well as the pharmacological activities of the plants discussed in the text are summarized in Table 1. The results obtained in different experimental model systems of photoaging are summarized in Fig. 2.

Scientific and common names, part of the plants used in the studies, identified bioactives and main pharmacological activities of the plants

 

Common or garden angelica (Angelica archangelia) belongs to the Apiaceae family and is commonly cultivated due to its edible stems and roots. It has also been widely used in traditional medicine by virtue of its properties against anxiety and dementia and by its ability to induce hair growth (Sun et al. 2016a). The main compound of Angelica archangelia (AA) root crude extract is chlorogenic acid (Sun et al. 2016a). Treatment of normal human dermal fibroblasts (NHDF) with crude AA extract immediately after UVB irradiation was shown to decrease intracellular reactive oxygen species (ROS) production in comparison with non-treated irradiated cells (Sun et al. 2016a). AA root extract prevented UVB-induced damage of extracellular matrix (ECM) through blockage of collagen degradation and induction of collagen production, as treatment of NHDF with this extract restrained the phosphorylation of MAPK/AP-1 family members and activated TGF-β signaling. As a consequence, AA extract inhibited UVB-induced production and activity of matrix metalloproteases MMP-1 and MMP-3, restored procollagen type 1 synthesis and decreased the levels of the pro-inflammatory cytokine IL-6 in NHDF (Sun et al. 2016a).

 

Rooibos (Aspalathus linearis)

Rooibos or red bush is a broom-like member of the Fabaceae family, the leaves and twigs of which are rich in the polyphenol aspalathin (Magcwebeba et al. 2016ba). Polyphenols are antioxidant molecules and are able to prevent excessive oxidative stress generated by accumulation of ROS (Saric and Sivamani 2016). Rooibos is originally from South Africa and has been traditionally used in treatment of skin diseases due to its antioxidant and anti-inflammatory properties (Magcwebeba et al. 2016b). Rooibos extract has also been used in antiaging cosmetics and treatment of patients with this formulation for 4 weeks was shown to decrease skin roughness and to improve the aspect of wrinkles (Gaspar et al. 2008). In an in vitro keratinocyte inflammatory UVB model, rooibos methanolic and aqueous extracts were shown to prevent accumulation of photodamage in HaCaT keratinocytes through indirect modulation of the inflammatory response (Magcwebeba et al. 2016b). Briefly, keratinocytes were exposed to UVB and further cultivated in the presence of the two different types of rooibos extract in different concentrations for 24 h. Results showed that both extracts were able to inhibit UVB-induced accumulation of pro-inflammatory intracellular IL-1α (icIL-1α) and to promote enhancement in the elimination of cells with increased levels of icIL-1α via apoptosis, protecting the cells against the cumulative damage caused by UVB (Magcwebeba et al. 2016b). In addition, a study was performed to test the anti-wrinkle properties of a cosmetic formulation containing a mixture of rooibos and tea extract (0.15% w/w) in middle-aged healthy women (Chuarienthong et al. 2010). Following application of the formulation twice a day during 28 consecutive days, parameters such as skin hydration and appearance of wrinkles were measured and the results were compared to the correspondent body areas tested before the treatment. The formulation containing rooibos and tea extracts was able to significantly decrease tissue wrinkles and slightly increase skin smoothness suggesting a potential role of rooibos extract to be used in cosmetic preparations (Chuarienthong et al. 2010).

Honeybush (Cyclopia spp.)

Honeybush is a group of leguminous plants that belong to the genus Cyclopia of the Fabaceae family. Honeybush plants grow in South Africa and their leaves, flowers and stems are commonly used for the preparation of teas and have been used in traditional medicine against skin disorders due to the high level of xanthones and flavanones (Gerber et al. 2015). The main bioactive compounds of honeybush are the xanthone mangiferin and the flavone hesperidin, which are polyphenols with high anti-inflammatory and antioxidant properties (Magcwebeba et al. 2016b). Topical administration of crude non-fermented and fermented Honeybush extract, but not of pure mangiferin and hesperidin, were able to inhibit UVB-induced edema in a study performed with hairless mice (Saric and Sivamani 2016). Furthermore, in the same study referred above for rooibos extract, aqueous honeybush extract was shown to have cytoprotective effects against UVB-induced oxidative stress (Magcwebeba et al. 2016b). In addition, treatment of HaCaT keratinocytes with honeybush methanol extracts after UVB treatment inhibited the accumulation of icIL-1α and reduced caspase-3 activity, consequently preventing apoptotic cell death (Magcwebeba et al. 2016b).

Tea plant (Camellia sinensis)

Tea is one of the most popular beverages in the world. White, green and black teas are products of the leaves, buds, and seeds from the tea plant Camellia sinensis, and differ in the way they are obtained and processed and, consequently, in the availability of bioactive compounds (Bosch et al. 2015). White tea is composed of young non-fermented leaves (Kim et al. 2015). Green tea is obtained by pan frying or steaming of leaves, a process that inactivates the endogenous polyphenol oxidase and increases the amount of caffeine (Lim et al. 2014; Lee et al. 2014a). Black tea is produced through fermentation/oxidation of the leaves and displays a high content of caffeine and tanins as well as of more complex polyphenols such as thearubigins and theaflavins which give it the brownish-red color (Kim et al. 2015).

The anti-photoaging effects of tea from Camellia sinensis have been proven in many studies (Suggs et al. 2014; Lim et al. 2014; Lee et al. 2014a; Kim et al. 2015). Lee and colleagues (2014) demonstrated that topical application of tea leaves extract to mice exposed to UVB ameliorated the appearance of wrinkles, decreased epidermal thickness, and reduced the expression and activity of MMP-3, leading to improvement of the ECM in comparison with UVB-irradiated non-treated animals (Lee et al. 2014a). In addition, this study showed that white tea and black tea, in general, were more efficient than green tea in preventing UVB-induced photoaging.

Oral administration of green tea seed extract (GTSE) to UVB-treated hairless mice decreased epidermal thickness allowing better skin hydration and recovered collagen density in a dose dependent manner (Lim et al. 2014). Results of treated animals revealed that GTSE, which contains catechins, gallic acid, caffeic acid and coumaric acid as its main bioactive compounds, is able to recover the activity of antioxidant enzymes, such as superoxide dismutase, catalase and glutathione peroxidase in a dose-dependent manner, in comparison to the skin of irradiated animals that were not treated with the extract. Finally, it was shown that GTSE decreased UVB-induced expression of MMP-1, MMP-3 and MMP-9 as well as increased the synthesis of collagen type 1 (Lim et al. 2014).

Altogether these data suggest the potential use of tea extracts in cosmetic formulations and as food supplements to be used against the damaging effects caused by UVB.

Bergamot (Citrus bergamia)

The protective effect of bergamot a polyphenol fraction (BPF) against UVB-induced damage of keratinocytes was studied by a group headed by Nisticò (Nisticò et al. 2015). It was shown that cultivation of HaCaT keratinocytes in the presence of BPF after UVB treatment leads to recovery of cell viability through modulation of the pro-inflammatory cytokine IL-1β via antioxidant mechanisms. Furthermore, treatment of cells with BPF was able to restore telomere length and telomerase activity in cells that received UVB irradiation suggesting that BPF has the ability to modulate signal transduction pathways related to immunoregulation and cell proliferation (Nisticò et al. 2015).

Grapefruit (Citrus x paradisi)

Grapefruit, a hybrid plant that belongs to the Rutaceae family originally from Central and South America is commonly used in general alimentation as well as in cosmetic formulations due to its vivid color and citric scent. Grapefruit is rich in phenolic compounds, among which gallic acid (GA) is the most abundant (Nobile et al. 2016). In a study conducted by Pérez-Sánchez and colleagues cultivation of human keratinocytes, prior to UVB irradiation, in the presence of grapefruit extract alone (12.5–100 µg/mL) or in combination with rosemary extract (12.5–100 µg/mL), which is also rich in GA, was investigated. Results demonstrated that grapefruit extract alone or in combination with rosemary extract is able to improve cell viability and to decrease UVB-induced intracellular ROS levels in a dose-dependent manner in comparison to irradiated non-treated cells (Pérez-Sánchez et al. 2014). These results suggest the potential use of grapefruit extract as an antioxidant in cosmetic formulations.

 

Abstract

Skin is continuously exposed to a variety of environmental stresses, including ultraviolet (UV) radiation. UVB is an inherent component of sunlight that crosses the epidermis and reaches the upper dermis, leading to increased oxidative stress, activation of inflammatory response and accumulation of DNA damage among other effects. The increase in UVB radiation on earth due to the destruction of stratospheric ozone poses a major environmental threat to the skin, increasing the risk of damage with long-term consequences, such as photoaging and photocarcinogenesis. Extracts from plants and natural compounds have been historically used in traditional medicine in the form of teas and ointments but the effect of most of these compounds has yet to be verified. Regarding the increasing concern of the population with issues related to quality of life and appearance, the cosmetic market for anti-aging and photoprotective products based on natural compounds is continuously growing, and there is increasing requirement of expansion on research in this field. In this review we summarized the most current and relevant information concerning plant extracts and natural compounds that are able to protect or mitigate the deleterious effects caused by photoaging in different experimental models.

Introduction

Skin is the outermost organ of the body and is subjected to environmental damage such as sunlight and pollution among others. Skin aging is the result of two synergistic mechanisms: intrinsic or chronological aging, a process that occurs not just to the skin but to all tissues and is a result of passage of time; and extrinsic aging, or photoaging, which is caused by repetitive exposure of the skin to damaging agents, especially sunlight (Naylor et al. 2011). UVB is the most dangerous component of sunlight. Due to its high energy, UVB is able to cross the epidermis and reach the upper dermis where is interacts with cellular chromophores, leading to DNA damage and increased oxidative stress (Trautinger 2001; Cavinato and Jansen-Dürr 2017). These events activate innumerous signaling pathways that lead to decreased collagen production, increased synthesis and activity of matrix metalloproteases (MMPs) which are responsible for connective tissue degradation, accumulation of senescent cells, synthesis and accumulation of the senescence-associated secretory phenotype (SASP) components and defective degradation of elastic fibers (Cavinato et al. 2016; Cavinato and Jansen-Dürr 2017) (Fig. 1). Macroscopically, these events result in the appearance of wrinkles, increased epidermal thickness with consequent increased dehydration, hyperpigmentation, sallowness, and loss of skin tone, which are the main characteristics of photoaged skin (Quan et al. 2004). The increment in UVB radiation on earth due to the destruction of the ozone layer, is a major environmental threat to the skin, increasing the risk of damage with long-term consequences, such as photoaging, photoimmunosuppression and photocarcinogenesis (Decean et al. 2016).

 

 

In an era that has been witnessing a significant increase in life expectancy and consequent growth of the elderly population, knowledge of physiological changes and diseases most frequently observed in older skin is particularly important (Kim et al. 2013). Moreover, the appearance of elderly skin and the increasing demand for therapeutic interventions to minimize aging manifestations has led to a renewed interest in this matter by researchers, pharmaceutical and cosmetic industries (Draelos 2000). The market for natural cosmetic products is one of the fastest growing in the world and according to a recent survey, the global demand for these personal care products is expected to increase around 9.6% until 2018 (source: Transparent Market Research, http://www.transparencymarketresearch.com/organic-personal-care-products.html). The fields of skincare research and pharmacological characterization of natural compounds are evolving together with the demand of the market (Tundis et al. 2015).

 

Natural compounds are used for dermatologic purposes both as oral dietary supplements as well as in topical cosmetic formulations (Allemann and Baumann 2009). The vast array of techniques currently available to investigate skin responsivity to multiple stimuli has brought about a new era in cosmetic and dermocosmetic development based on a robust understanding of skin physiology and its varied responses to commonly encountered environmental insults (Dreno et al. 2014). The importance of cosmetic research is not only related to improving the skin overall appearance during aging, but also aims to offer better quality of life acting through prevention and treatment of skin disorders related to the aging process (Kraft and Lynde 2005). Several active ingredients have been identified as regulatory elements of skin homeostasis, with potential cosmetic and/or dermatological applications (Gaspar et al. 2008; Watson et al. 2009; Kanlayavattanakul and Lourith 2010; Anunciato and da Rocha Filho 2012); however, the effectiveness of many formulations has yet to be confirmed. Moreover, considering the diversity of plants and natural compounds available, this field of study has large potential for growth. Given this fact, a discussion of all the currently available literature related to natural compounds and plant extracts used in dermatology would exceed the scope of this manuscript. In this article, we will provide a comprehensive review of the most relevant publications related to the use of plant extracts and natural compounds to prevent or ameliorate the effects of UVB irradiation on the skin.

Plant extracts used against UVB-induced photodamage

In this review, the most important and recent studies concerning plant species with anti-photoaging activities are described along with information on pharmacological effects of the relevant extracts against molecular processes driving skin aging in cellular and animal models. The scientific and common names, part of the plants used in the studies, identified bioactives as well as the pharmacological activities of the plants discussed in the text are summarized in Table 1. The results obtained in different experimental model systems of photoaging are summarized in Fig. 2.

Scientific and common names, part of the plants used in the studies, identified bioactives and main pharmacological activities of the plants

 

Common or garden angelica (Angelica archangelia) belongs to the Apiaceae family and is commonly cultivated due to its edible stems and roots. It has also been widely used in traditional medicine by virtue of its properties against anxiety and dementia and by its ability to induce hair growth (Sun et al. 2016a). The main compound of Angelica archangelia (AA) root crude extract is chlorogenic acid (Sun et al. 2016a). Treatment of normal human dermal fibroblasts (NHDF) with crude AA extract immediately after UVB irradiation was shown to decrease intracellular reactive oxygen species (ROS) production in comparison with non-treated irradiated cells (Sun et al. 2016a). AA root extract prevented UVB-induced damage of extracellular matrix (ECM) through blockage of collagen degradation and induction of collagen production, as treatment of NHDF with this extract restrained the phosphorylation of MAPK/AP-1 family members and activated TGF-β signaling. As a consequence, AA extract inhibited UVB-induced production and activity of matrix metalloproteases MMP-1 and MMP-3, restored procollagen type 1 synthesis and decreased the levels of the pro-inflammatory cytokine IL-6 in NHDF (Sun et al. 2016a).

 

Rooibos (Aspalathus linearis)

Rooibos or red bush is a broom-like member of the Fabaceae family, the leaves and twigs of which are rich in the polyphenol aspalathin (Magcwebeba et al. 2016ba). Polyphenols are antioxidant molecules and are able to prevent excessive oxidative stress generated by accumulation of ROS (Saric and Sivamani 2016). Rooibos is originally from South Africa and has been traditionally used in treatment of skin diseases due to its antioxidant and anti-inflammatory properties (Magcwebeba et al. 2016b). Rooibos extract has also been used in antiaging cosmetics and treatment of patients with this formulation for 4 weeks was shown to decrease skin roughness and to improve the aspect of wrinkles (Gaspar et al. 2008). In an in vitro keratinocyte inflammatory UVB model, rooibos methanolic and aqueous extracts were shown to prevent accumulation of photodamage in HaCaT keratinocytes through indirect modulation of the inflammatory response (Magcwebeba et al. 2016b). Briefly, keratinocytes were exposed to UVB and further cultivated in the presence of the two different types of rooibos extract in different concentrations for 24 h. Results showed that both extracts were able to inhibit UVB-induced accumulation of pro-inflammatory intracellular IL-1α (icIL-1α) and to promote enhancement in the elimination of cells with increased levels of icIL-1α via apoptosis, protecting the cells against the cumulative damage caused by UVB (Magcwebeba et al. 2016b). In addition, a study was performed to test the anti-wrinkle properties of a cosmetic formulation containing a mixture of rooibos and tea extract (0.15% w/w) in middle-aged healthy women (Chuarienthong et al. 2010). Following application of the formulation twice a day during 28 consecutive days, parameters such as skin hydration and appearance of wrinkles were measured and the results were compared to the correspondent body areas tested before the treatment. The formulation containing rooibos and tea extracts was able to significantly decrease tissue wrinkles and slightly increase skin smoothness suggesting a potential role of rooibos extract to be used in cosmetic preparations (Chuarienthong et al. 2010).

Honeybush (Cyclopia spp.)

Honeybush is a group of leguminous plants that belong to the genus Cyclopia of the Fabaceae family. Honeybush plants grow in South Africa and their leaves, flowers and stems are commonly used for the preparation of teas and have been used in traditional medicine against skin disorders due to the high level of xanthones and flavanones (Gerber et al. 2015). The main bioactive compounds of honeybush are the xanthone mangiferin and the flavone hesperidin, which are polyphenols with high anti-inflammatory and antioxidant properties (Magcwebeba et al. 2016b). Topical administration of crude non-fermented and fermented Honeybush extract, but not of pure mangiferin and hesperidin, were able to inhibit UVB-induced edema in a study performed with hairless mice (Saric and Sivamani 2016). Furthermore, in the same study referred above for rooibos extract, aqueous honeybush extract was shown to have cytoprotective effects against UVB-induced oxidative stress (Magcwebeba et al. 2016b). In addition, treatment of HaCaT keratinocytes with honeybush methanol extracts after UVB treatment inhibited the accumulation of icIL-1α and reduced caspase-3 activity, consequently preventing apoptotic cell death (Magcwebeba et al. 2016b).

Tea plant (Camellia sinensis)

Tea is one of the most popular beverages in the world. White, green and black teas are products of the leaves, buds, and seeds from the tea plant Camellia sinensis, and differ in the way they are obtained and processed and, consequently, in the availability of bioactive compounds (Bosch et al. 2015). White tea is composed of young non-fermented leaves (Kim et al. 2015). Green tea is obtained by pan frying or steaming of leaves, a process that inactivates the endogenous polyphenol oxidase and increases the amount of caffeine (Lim et al. 2014; Lee et al. 2014a). Black tea is produced through fermentation/oxidation of the leaves and displays a high content of caffeine and tanins as well as of more complex polyphenols such as thearubigins and theaflavins which give it the brownish-red color (Kim et al. 2015).

The anti-photoaging effects of tea from Camellia sinensis have been proven in many studies (Suggs et al. 2014; Lim et al. 2014; Lee et al. 2014a; Kim et al. 2015). Lee and colleagues (2014) demonstrated that topical application of tea leaves extract to mice exposed to UVB ameliorated the appearance of wrinkles, decreased epidermal thickness, and reduced the expression and activity of MMP-3, leading to improvement of the ECM in comparison with UVB-irradiated non-treated animals (Lee et al. 2014a). In addition, this study showed that white tea and black tea, in general, were more efficient than green tea in preventing UVB-induced photoaging.

Oral administration of green tea seed extract (GTSE) to UVB-treated hairless mice decreased epidermal thickness allowing better skin hydration and recovered collagen density in a dose dependent manner (Lim et al. 2014). Results of treated animals revealed that GTSE, which contains catechins, gallic acid, caffeic acid and coumaric acid as its main bioactive compounds, is able to recover the activity of antioxidant enzymes, such as superoxide dismutase, catalase and glutathione peroxidase in a dose-dependent manner, in comparison to the skin of irradiated animals that were not treated with the extract. Finally, it was shown that GTSE decreased UVB-induced expression of MMP-1, MMP-3 and MMP-9 as well as increased the synthesis of collagen type 1 (Lim et al. 2014).

Altogether these data suggest the potential use of tea extracts in cosmetic formulations and as food supplements to be used against the damaging effects caused by UVB.

Bergamot (Citrus bergamia)

The protective effect of bergamot a polyphenol fraction (BPF) against UVB-induced damage of keratinocytes was studied by a group headed by Nisticò (Nisticò et al. 2015). It was shown that cultivation of HaCaT keratinocytes in the presence of BPF after UVB treatment leads to recovery of cell viability through modulation of the pro-inflammatory cytokine IL-1β via antioxidant mechanisms. Furthermore, treatment of cells with BPF was able to restore telomere length and telomerase activity in cells that received UVB irradiation suggesting that BPF has the ability to modulate signal transduction pathways related to immunoregulation and cell proliferation (Nisticò et al. 2015).

Grapefruit (Citrus x paradisi)

Grapefruit, a hybrid plant that belongs to the Rutaceae family originally from Central and South America is commonly used in general alimentation as well as in cosmetic formulations due to its vivid color and citric scent. Grapefruit is rich in phenolic compounds, among which gallic acid (GA) is the most abundant (Nobile et al. 2016). In a study conducted by Pérez-Sánchez and colleagues cultivation of human keratinocytes, prior to UVB irradiation, in the presence of grapefruit extract alone (12.5–100 µg/mL) or in combination with rosemary extract (12.5–100 µg/mL), which is also rich in GA, was investigated. Results demonstrated that grapefruit extract alone or in combination with rosemary extract is able to improve cell viability and to decrease UVB-induced intracellular ROS levels in a dose-dependent manner in comparison to irradiated non-treated cells (Pérez-Sánchez et al. 2014). These results suggest the potential use of grapefruit extract as an antioxidant in cosmetic formulations.

 

 

 

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