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Flavonoid-Rich Nutrients for the Skin
Abstract
Flavonoids are a group of widespread plant constituents available from dietary sources such as cocoa, green tea, soy, berries,
or other fruits like apples, lemons, cherries, plums, and peaches. There is evidence that flavonoid-rich products contribute
to the protection of skin against UV-induced damage at the molecular and cellular level and that they may as well improve
overall skin conditions. Regular intake or topical application confers significantly to photoprotection and helps maintaining
skin health by improving skin structure and function. Photoprotective effects mediated by flavonoids are moderate but likely
contribute to permanent, overall protection. Effects are comparable to those reported for other dietary constitutents such
as carotenoids and other antioxidants.
... This photoprotection effect by flavonoids increases the hydration level. 38 Products having flavonoids in excess amount protect skin and improve the overall condition of it. 39 Polyphenols present in the extract may also improve moisture contents of skin. ...
Background:
Antioxidants are widely used in cosmetic products as they have beneficial effects on skin and prevent skin from harmful effects of environment. Albizia lebbeck has a significant potential to be used in cosmeceuticals due to its antioxidant activity.
Objectives:
The aim of this study was to formulate a stable and effective o/w emulsion based emulgel containing Albizia lebbeck bark extract which have considerable antioxidant activity.
Methodology:
Antioxidant activity of Albizia lebbeck bark extract was determined by DPPH (2,2-diphenyl-1-picrylhydrazyl) method. Emulgel containing 3% extract was developed by mixing o/w emulsion in Carbopol gel alongwith a placebo emulgel without extract (base). In-vitro evaluation of these emulgels i.e. liquefaction, color, phase separation, centrifugation and pH change; were carried out for a period of 8 weeks at different storage conditions i.e., 8ºC, 25ºC, 40ºC and 40ºC & 75 % relative humidity (RH). In-vivo evaluation of emulgels was carried out on 13 healthy female volunteers by measuring various parameters of skin i.e. melanin level, erythema level, moisture content, sebum content and elasticity at regular time intervals after applying emulgel (both base and test formulation) for 8 weeks.
Results:
Antioxidant activity of Albizia lebbeck bark extract was 84.7%. Both emulgels (base and test formulation) were stable at all storage conditions. Statistical analysis showed that test formulation produced significant effects (p<0.05) on melanin, erythema level, moisture content, sebum level and elasticity of skin.
Conclusion:
It can be concluded that a stable topical emulgel containing 3% Albizia lebbeck bark extract has significant antioxidant effects on human skin.
... HepG2 cells submitted to oxidative stress induced by tert-butylhydroperoxide (t-BOOH) (Martin et al., 2008). There is also evidence that flavonoid-rich products contribute to the protection of skin against UV-induced damage at the molecular and cellular level, thereby improving overall skin conditions (Stahl, 2011). This finding has also been observed by Jorge et al. (2011) who showed that long term cocoa ingestion leads to an increased resistance against UV-induced erythema and a lowered transepidermal water loss (Jorge et al., 2011). ...
The cacao, as part of the wonderful nature, provides the mankind a wide variety of valuable food products and health benefits. The most known and universally relished product derived from this fruit is chocolate, an amazing and unique food for the human nutrition with records of consumption of similar products dating to 1000 years B.C. In fact, the cocoa is a complex food that includes over 300 different components. This review is designed to inform scientists, technicians, academicians, farmers, and interested communities of numerous studies that have been conducted worldwide to investigate the properties of various cocoa constituents, their relations to human health, and their potential role in the prevention and treatment of many medical conditions. The general population, for example in Brazil, despite being one of the major producers of cocoa, is poorly informed of the significant and beneficial properties of cocoa. The present review covers important topics linking cocoa to human health and show the state of the art of effect of cocoa in different systems that comprise the human body. The paper is organized based on the main human organ system and includes: Cardiovascular / Circulatory, Neurological / Nervous, Oral health, Endocrine, Lymphatic and Immunological, Respiratory, Reproductive, Dermatological systems. Scientific findings tend to confirm the historic designation of cacao as “food of the Gods”.
Carica papaya is an economically vivacious plant of tropical and subtropical regions, cultivated in over 50 countries across the world with 6.8 million tons production. Papaya holds a broad spectrum of phytochemicals, including polysaccharides, vitamins, minerals, enzymes, proteins, glycosides, saponins, flavonoids, and phytosterols. These bioactive components are responsible for the pharmacological properties of this auspicious plant and demonstrate its importance in daily intake and alimentation. Additionally, it is an excellent aid to digestion and also hydrolyzing gluten, which is an important aspect for dyspeptic and celiac disease patients. Papaya acts as an antioxidant, antimicrobial, anticarminative, anticancer, and has hepato-protective, immunological, and other therapeutic attributes. The seed and pulp of papaya have bacteriostatic effects against several enteropathogens, such as Bacillus subtilus and E. coli. In the current review, pharmacological attributes, nutritional value of papaya, and medicinal properties of its various parts have been elaborated to provide collective information on this multipurpose commercial plant. Moreover, its role in the production of alcohol and carboxymethyl cellulose is also the limelight of the article. Furthermore, the present review article summarizes the literature pertaining to its pharmakinetics and also allies its health claims. Yet, the authors are still of the view that further research needs to be conducted for meticulousness.
Skin functions and healthy appearance depend on a sufficient supply of essential nutrients. The relationship between nutrition and skin has become a hot topic that is exciting researchers and clinicians worldwide. Intervention studies indicate that it is in fact possible to manipulate and to delay skin aging and to improve skin conditions through supplementation with selected nutritional supplements. It has been shown that diet-based anti-aging strategies are most effective when directed against extrinsic skin aging. New insights into the effects of orally-administered, biologically active molecules on skin functions have stimulated a continuously growing interest in the development of nutritional supplements and functional food products to benefit human skin. This article attempts to provide a briefly overview to some of the healthy and protective substances used as functional food.
Ultraviolet (UV) radiation is one of the most abundant carcinogens in our environment, and the development of non-melanoma skin cancers, the most common type of human malignancy worldwide, represents one of the major consequences of excessive exposure. Because of growing concerns that the level of UV radiation is increasing as a result of depletion of the stratospheric ozone and climate change, the development of strategies for protection of the skin is an urgent need. Many phytochemicals that belong to various families of secondary metabolites, such as alkaloids (caffeine, sanguinarine), flavonoids [(-)-epigallocatechin 3-gallate, genistein, silibinin], carotenoids ( beta-carotene, lycopene), and isothiocyanates (sulforaphane), offer exciting platforms for the development of such protective strategies. These phytochemicals have been consumed by humans for many centuries as part of plant-rich diets and are presumed to be of low toxicity, an essential requirement for a chemoprotective agent. Mechanistically, they affect multiple signalling pathways and protect against UV radiation-inflicted damage by their ability to act as direct and indirect antioxidants, as well as anti-inflammatory and immunomodulatory agents. Such "pluripotent character" is a critical prerequisite for an agent that is designed to counteract the multiple damaging effects of UV radiation. Especially attractive are inducers of the Keap1/Nrf2/ARE pathway, which controls the gene expression of proteins whose activation leads to enhanced protection against oxidants and electrophiles. Such protection is comprehensive, long-lasting, and unlikely to cause pro-oxidant effects or interfere with the synthesis of vitamin D.
Mild cases of atopic dermatitis (AD) generally improve with standard treatment. However, standard treatment fails many patients with recalcitrant AD skin lesions. Study results in animal models have demonstrated that the administration of tea (ie, green, black, or oolong) has suppressed type I and type IV allergic reactions.
To test the effectiveness of oolong tea in the treatment of recalcitrant AD.
Although 121 patients with recalcitrant AD were enrolled in the study, 118 patients completed the open study.
Patients were asked to maintain their dermatological treatment. However, they were also instructed to drink oolong tea made from a 10-g teabag placed in 1000 mL of boiling water and steeped for 5 minutes. This amount was then divided into 3 equal servings and 1 serving was drunk daily after 3 regular meals. Photographs of 2 or 3 representative lesion sites were taken at baseline and at 1 and 6 months and the severity of pruritus was assessed on a 6-point Lickert-like scale ranging from markedly improved (>50% improvement) to worsened.
After 1 month of treatment 74 (63%) of the 118 patients showed marked to moderate improvement of their condition. The beneficial effect was first noticed after 1 or 2 weeks of treatment. A good response to treatment was still observed in 64 patients (54%) at 6 months.
The therapeutic efficacy of oolong tea in recalcitrant AD may well be the result of the antiallergic properties of tea polyphenols.
An attempt has been made to assess the UV‐B‐protective capacity of phenolic compounds accumulated in superficial structures
of plants using apple fruit as a model. Two apple (Malus domestica Borkh.) cultivars (Braeburn and Granny Smith) differing in response to high fluxes of solar radiation were selected and exposed
to increasing doses of UV‐B radiation. The extent of UV‐B‐induced damage to photosystem II of apple skin correlated with its
quercetin glycoside (but not anthocyanin) content. Granny Smith apples did not demonstrate a pronounced response to high sunlight
in terms of the accumulation of phenolic substances in the skin and exhibited similar patterns of Fo, Fm, and Fv/Fm changes in the course of UV‐B irradiation both on sun‐exposed and shaded surfaces of a fruit. Unlike Granny Smith, Braeburn
fruits were characterized by a significant accumulation of quercetin glycosides in sun‐exposed skin, however, shaded skin
contained these compounds in similar amounts to those in Granny Smith. Accordingly, photosystem II in sun‐exposed skin of
Braeburn apples was resistant to high doses of UV‐B radiation (up to 97 kJ m–2), whereas the susceptibility of the photosynthetic apparatus in shaded skin of Braeburn to UV‐B‐induced damage was much higher
and similar to that of both sun‐exposed and shaded skin of Granny Smith fruits. Anthocyanins, at least in the amounts found
in Braeburn, did not show an additional effect in UV‐B protection.
Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases such as cancer and cardiovascular diseases is emerging. The health effects of polyphenols depend on the amount consumed and on their bioavailability. In this article, the nature and contents of the various polyphenols present in food sources and the influence of agricultural practices and industrial processes are reviewed. Estimates of dietary intakes are given for each class of polyphenols. The bioavailability of polyphenols is also reviewed, with particular focus on intestinal absorption and the influence of chemical structure (eg, glycosylation, esterification, and polymerization), food matrix, and excretion back into the intestinal lumen. Information on the role of microflora in the catabolism of polyphenols and the production of some active metabolites is presented. Mechanisms of intestinal and hepatic conjugation (methylation, glucuronidation, sulfation), plasma transport, and elimination in bile and urine are also described. Pharmacokinetic data for the various polyphenols are compared. Studies on the identification of circulating metabolites, cellular uptake, intracellular metabolism with possible deconjugation, biological properties of the conjugated metabolites, and specific accumulation in some target tissues are discussed. Finally, bioavailability appears to differ greatly between the various polyphenols, and the most abundant polyphenols in our diet are not necessarily those that have the best bioavailability profile. A thorough knowledge of the bioavailability of the hundreds of dietary polyphenols will help us to identify those that are most likely to exert protective health effects.
The concept of systemic photoprotection by dietary means is gaining momentum. Skin is continuously exposed to ultraviolet (UV) radiation, the major cause of skin disorders such as sunburn, photodamage, and nonmelanoma skin cancer. Most of the erythemal annual UV dose is encountered under nonvacation conditions, when no sunscreen is applied. In the absence of topically added compounds, skin protection depends solely on endogenous defense. Micronutrients can act as UV absorbers, as antioxidants, or can modulate signaling pathways elicited upon UV exposure. UV-induced erythema is a suitable parameter to assess photoprotection. Dietary protection is provided by carotenoids, tocopherols, ascorbate, flavonoids, or n-3 fatty acids, contributing to maintenance resistance as part of lifelong protection.
An increasing body of epidemiologic evidence supports the concept that diets rich in fruits and vegetables can promote health and attenuate, or delay, the onset of various diseases. Epidemiologic data support the idea that these health benefits are causally linked to the consumption of certain flavonoids present in fruit and vegetables. In the context of cardiovascular health, a particular group of flavonoids, namely, the flavan-3-ols (flavanols), has received attention. Flavanol-rich, plant-derived foods and beverages include wine, tea, and various fruits and berries, as well as cocoa and cocoa products. Numerous dietary intervention studies in humans and animals indicate that flavanol-rich foods and beverages might exert cardioprotective effects with respect to vascular function and platelet reactivity. This review discusses the bioactivity of flavanols in the context of cardiovascular health, with respect to their bioavailability, their antioxidant properties, and their vascular effects.
Plant extracts have been widely used as topical applications for wound-healing, anti-aging, and disease treatments. Examples of these include ginkgo biloba, echinacea, ginseng, grape seed, green tea, lemon, lavender, rosemary, thuja, sarsaparilla, soy, prickly pear, sagebrush, jojoba, aloe vera, allantoin, feverwort, bloodroot, apache plume, and papaya. These plants share a common character: they all produce flavonoid compounds with phenolic structures. These phytochemicals are highly reactive with other compounds, such as reactive oxygen species and biologic macromolecules, to neutralize free radicals or initiate biological effects. A short list of phenolic phytochemicals with promising properties to benefit human health includes a group of polyphenol compounds, called catechins, found in green tea. This article summarizes the findings of studies using green tea polyphenols as chemopreventive, natural healing, and anti-aging agents for human skin, and discusses possible mechanisms of action.
Dietary antioxidants contribute to endogenous photoprotection and are important for the maintenance of skin health. In the present study, 2 groups of women consumed either a high flavanol (326 mg/d) or low flavanol (27 mg/d) cocoa powder dissolved in 100 mL water for 12 wk. Epicatechin (61 mg/d) and catechin (20 mg/d) were the major flavanol monomers in the high flavanol drink, whereas the low flavanol drink contained 6.6 mg epicatechin and 1.6 mg catechin as the daily dose. Photoprotection and indicators of skin condition were assayed before and during the intervention. Following exposure of selected skin areas to 1.25 x minimal erythemal dose (MED) of radiation from a solar simulator, UV-induced erythema was significantly decreased in the high flavanol group, by 15 and 25%, after 6 and 12 wk of treatment, respectively, whereas no change occurred in the low flavanol group. The ingestion of high flavanol cocoa led to increases in blood flow of cutaneous and subcutaneous tissues, and to increases in skin density and skin hydration. Skin thickness was elevated from 1.11 +/- 0.11 mm at wk 0 to 1.24 +/- 0.13 mm at wk 12; transepidermal water loss was diminished from 8.7 +/- 3.7 to 6.3 +/- 2.2 g/(h x m2) within the same time frame. Neither of these variables was affected in the low flavanol cocoa group. Evaluation of the skin surface showed a significant decrease of skin roughness and scaling in the high flavanol cocoa group compared with those at wk 12. Dietary flavanols from cocoa contribute to endogenous photoprotection, improve dermal blood circulation, and affect cosmetically relevant skin surface and hydration variables.
Long term cocoa ingestion leads to an increased resistance against UV-induced erythema and a lowered transepidermal water loss.
To investigate the acute effects of a single dose of cocoa rich in flavanols on dermal microcirculation.
In a crossover design study, 10 healthy women ingested a cocoa drink (100 ml) with high (329 mg) or low (27 mg) content of flavanols. The major flavanol monomer in both drinks was epicatechin, 61 mg in the high flavanol, and 6.6 mg in the low flavanol product per 100 ml. Dermal blood flow and oxygen saturation of hemoglobin were examined by laser Doppler flowmetry and spectroscopically at 1 mm skin depth at t = 0, 1, 2, 4, and 6 h. At the same time points, plasma levels of total epicatechin (free compound plus conjugates) were measured by means of HPLC.
Subsequent to the intake of high flavanol cocoa, dermal blood flow was significantly increased by 1.7-fold at t = 2 h and oxygen saturation was elevated 1.8-fold. No statistically significant changes were found upon intake of low flavanol cocoa. Maximum plasma levels of total epicatechin were observed 1 h after ingestion of the high flavanol cocoa drink, 11.6 +/- 7.4 nmol/l at baseline, and 62.9 +/- 35.8 nmol/l at 1 h. No change of total epicatechin was found in the low flavanol group.
Flavanol-rich cocoa consumption acutely increases dermal blood flow and oxygen saturation.
Polyphenolic phytochemicals are ubiquitous in plants, in which they function in various protective roles. A 'recommended' human diet contains significant quantities of polyphenolics, as they have long been assumed to be 'antioxidants' that scavenge excessive, damaging, free radicals arising from normal metabolic processes. There is recent evidence that polyphenolics also have 'indirect' antioxidant effects through induction of endogenous protective enzymes. There is also increasing evidence for many potential benefits through polyphenolic-mediated regulation of cellular processes such as inflammation. Inductive or signalling effects may occur at concentrations much lower than required for effective radical scavenging. Over the last 2-3 years, there have been many exciting new developments in the elucidation of the in vivo mechanisms of the health benefits of polyphenolics. We summarise the current knowledge of the intake, bio-availability and metabolism of polyphenolics, their antioxidant effects, regulatory effects on signalling pathways, neuro-protective effects and regulatory effects on energy metabolism and gut health.
Given that flavonoids are known for their ultraviolet (UV)B photoprotective properties in plants that contain them, we chose to study quercetin (1) and rutin (2) as agents that could potentially be used in sunscreen products. These two substances proved to behave in similar ways. When incorporated in oil-in-water emulsions, at a concentration of 10% (w/w), 1 and 2 give sun protection factor (SPF) values similar to that of homosalate, a standard substance. These two flavonoids also provided a non-negligible level of photoprotection in the UVA range. When used in association with titanium dioxide, the SPF obtained was around 30.
The human organism depends on an adequate energy supply provided by major dietary components, protein, carbohydrates and lipids. However, minor constituents such as vitamins, minerals and specific fatty acids are required in a healthy diet as well. Secondary plant compounds are ingested with food and enter the systemic circulation. These are not essential in the strict sense of a vitamin, but some of these compounds exhibit distinct biological activities. Among them are terpenoids and polyphenols such as carotenoids, tocopherols, and fla-vonoids [1-3] which are known to be efficient antioxidant micronutrients. As the exterior barrier of the body, the skin is in direct contact with the environment. This organ is exposed to oxygen and light, conditions under which reactive oxygen species (ROS) are generated. Photooxidative stress is involved in processes of photoaging and photocarcinogen-esis, and plays a major role in the pathogenesis of photodermatoses [4]. As any other tissue, skin depends on an optimal supply of nutritive compounds. Skin benefits from dietary antioxidants capable of scavenging reactive intermediates generated under the condition of photooxidative stress [5-7]. Micronutrients may also act as UV absorbers, or modulate signaling pathways elicited upon UV exposure [8-10]. In plants, minor constituents play an important role in protection against excess light. Besides acting as accessory pigments, carotenoids are associated with photoprotection [11], being involved in the dissipation of excess light energy through the xanthophyll cycle, quenching excited triplet state molecules and singlet oxygen. Based on their structural features which determine their physicochemical properties, carot-enoids, flavonoids, and vitamins E and C are also suitable compounds for photoprotection in humans [6].
Chemical antioxidant activity assays are used extensively to evaluate the potential bioactivity of plant foods and their phytochemical constituents, but they do not mimic the complexity of biological systems. The cellular antioxidant activity (CAA) activity assay was developed to be a more biologically relevant model to measure antioxidant activity. Structure-activity relationships of flavonoids have been determined in many chemistry antioxidant activity assays, and they vary with the protocols. The objective of this study was to determine structure-activity relationships of selected flavonoids in the CAA assay. The structures that conferred flavonoids with the most antioxidant activity in the CAA assay were a 3',4'- o-dihydroxyl group in the B-ring, a 2,3-double bond combined with a 4-keto group in the C-ring, and a 3-hydroxyl group. Isoflavones had no cellular antioxidant activity. Flavanols with a galloyl moiety had higher antioxidant activity than those without, and a B-ring 3',4',5'-trihydroxyl group further improved their efficacy. ORAC values for flavonoids were not related to their CAA values. Knowledge of structure-activity relationships in the CAA assay may be helpful in assessing potential in vivo antioxidant activity of flavonoids.
Flavonoids are multi-active components used in common cosmetics primarily for antioxidant and soothing actions. Despite this, their multi-active properties are far from being fully used. It is well known that many flavonoids provide protection from telangiectasias and petechias caused by ruptured blood vessels. Thus, the notion of a "strengthening" effect of these compounds on blood vessel walls is common. The activity of flavonoids on skin blood vessels is complex. Three main components of their activity can be distinguished: blood vessel protection, platelet aggregation prevention, and capillary permeability decrease. Each of these components is realized with the participation of several mechanisms differing on the types of receptors that the flavonoids affect. Some of them consist of a direct action on the enzymes responsible for the synthesis of substances of tissue hormone character, such as thromboxanes, histamine, or platelet activating factor. The mechanisms based on less or more indirect activity can also be met. At least 11 points for activity can be distinguished among flavonoids' actions on blood vessels.
Flavonoids and their polymers constitute a large class of food constituents, many of which alter metabolic processes and have a positive impact on health. Flavonoids are a subclass of polyphenols. They generally consist of two aromatic rings, each containing at least one hydroxyl, which are connected through a three-carbon "bridge" and become part of a six-member heterocyclic ring. The flavonoids are further divided into subclasses based on the connection of an aromatic ring to the heterocyclic ring, as well as the oxidation state and functional groups of the heterocyclic ring. Within each subclass, individual compounds are characterized by specific hydroxylation and conjugation patterns. Many flavonoids in foods also occur as large molecules (tannins). These include condensed tannins (proanthocyanidins), derived tannins and hydrolysable tannins. For proanthocyanidins, three subclasses (15 characterized) have been identified in foods. Monomers are connected through specific carbon-carbon and ether linkages to form polymers. Derived tannins are formed during food handling and processing, and found primarily in black and oolong teas. Flavonoids are widely distributed in nature, albeit not uniformly. As a result, specific groups of foods are often rich sources of one or more subclasses of these polyphenols. The polyphenolic structure of flavonoids and tannins renders them quite sensitive to oxidative enzymes and cooking conditions. Scientists in several countries have estimated intakes of a few subclasses of flavonoids from limited food composition databases. These observations suggest large differences in consumption, due in part to cultural and food preferences among populations of each country.
Several environmental and genetic factors are involved in skin cancer induction, however exposure to chemical carcinogens and solar ultraviolet (UV) radiation are primarily responsible for several skin diseases including skin cancer. Chronic exposure of solar UV radiation to the skin leads to basal cell and squamous cell carcinoma, and melanoma. Chemoprevention of skin cancer by consumption of naturally occurring botanicals appears a practical approach and therefore world-wide interest is considerably increasing to use these botanicals. Sunscreens are useful but their protection is not ideal because of inadequate use, incomplete spectral protection and toxicity. Silymarin, a plant flavonoid isolated from the seeds of milk thistle (Silybum marianum), has been shown to have chemopreventive effects against chemical carcinogenesis as well as photocarcinogenesis in various animal tumor models. Topical treatment of silymarin inhibited 7,12-dimethylbenz(a)anthracene-initiated and several tumor promoters, like 12-O-tetradecanoylphorbol-13-acetate, mezerein, benzoyal peroxide and okadaic acid, induced skin carcinogenesis in mouse models. Similarly, silymarin also prevented UVB-induced skin carcinogenesis. Wide range of in vivo mechanistic studies indicated that silymarin possesses antioxidant, anti-inflammatory and immunomodulatory properties which may lead to the prevention of skin cancer in in vivo animal models. The available experimental information suggests that silymarin is a promising chemopreventive and pharmacologically safe agent which can be exploited or tested against skin cancer in human system. Moreover, silymarin may favorably supplement sunscreen protection and provide additional anti-photocarcinogenic protection.
Endothelial dysfunction is the pathophysiologic principle involved in the initiation and progression of arteriosclerosis, thus endothelial function serves as a "barometer" for cardiovascular health that can be used for the evaluation of new therapeutic strategies. This review provides an introduction to the concept of endothelial dysfunction, and it explores the importance of this prognostic marker in the context of clinical, dietary interventions in humans. Moreover, we summarize and evaluate the findings of various clinical trials that demonstrated an improvement of endothelial dysfunction in subjects with cardiovascular risk factors after the acute and chronic consumption of flavanol-rich foods, including cocoa products, red wine, and tea.
Exposure of the skin to ultraviolet (UV) radiation, particularly its UV-B component (280-320 nm), from the sun results in erythema, edema, hyperplasia, hyperpigmentation, sunburn cells, immunosuppression, photoaging, and skin cancer. Amongst these various adverse effects of UV-B radiation, skin cancer and photoaging are of great concern. More recent changes in lifestyle have led to a significant increase in the amount of UV-B radiation people receive leading to a surge in the incidence of skin cancer and photoaging. As these trends are likely to continue in the foreseeable future, the adverse effect of UV-B has become a major human health concern. Therefore, development of novel strategies to reduce the occurrence of skin cancer and delay the process of photoaging are highly desirable goals. One approach to reduce their occurrence is through photochemoprevention, which we define as the use of agents capable of ameliorating the adverse effects of UV-B on the skin. Photochemoprevention via use of botanical antioxidants, present in the common diet of human have gained considerable attention as photochemopreventive agents for human use. Many such agents have also found a place in skin care products. This review will focus on the effects of selected botanical antioxidants in the prevention of photocarcinogenesis and photoaging.
Reactive oxygen species (ROS) and reactive nitrogen species (RNS, e.g. nitric oxide, NO(*)) are well recognised for playing a dual role as both deleterious and beneficial species. ROS and RNS are normally generated by tightly regulated enzymes, such as NO synthase (NOS) and NAD(P)H oxidase isoforms, respectively. Overproduction of ROS (arising either from mitochondrial electron-transport chain or excessive stimulation of NAD(P)H) results in oxidative stress, a deleterious process that can be an important mediator of damage to cell structures, including lipids and membranes, proteins, and DNA. In contrast, beneficial effects of ROS/RNS (e.g. superoxide radical and nitric oxide) occur at low/moderate concentrations and involve physiological roles in cellular responses to noxia, as for example in defence against infectious agents, in the function of a number of cellular signalling pathways, and the induction of a mitogenic response. Ironically, various ROS-mediated actions in fact protect cells against ROS-induced oxidative stress and re-establish or maintain "redox balance" termed also "redox homeostasis". The "two-faced" character of ROS is clearly substantiated. For example, a growing body of evidence shows that ROS within cells act as secondary messengers in intracellular signalling cascades which induce and maintain the oncogenic phenotype of cancer cells, however, ROS can also induce cellular senescence and apoptosis and can therefore function as anti-tumourigenic species. This review will describe the: (i) chemistry and biochemistry of ROS/RNS and sources of free radical generation; (ii) damage to DNA, to proteins, and to lipids by free radicals; (iii) role of antioxidants (e.g. glutathione) in the maintenance of cellular "redox homeostasis"; (iv) overview of ROS-induced signaling pathways; (v) role of ROS in redox regulation of normal physiological functions, as well as (vi) role of ROS in pathophysiological implications of altered redox regulation (human diseases and ageing). Attention is focussed on the ROS/RNS-linked pathogenesis of cancer, cardiovascular disease, atherosclerosis, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases (Alzheimer's disease and Parkinson's disease), rheumatoid arthritis, and ageing. Topics of current debate are also reviewed such as the question whether excessive formation of free radicals is a primary cause or a downstream consequence of tissue injury.
Analytical data are reported for 20 flavonoids (as aglycones) determined for more than 60 fresh fruits, vegetables, and nuts collected from four regions across the United States at two times of the year. Sample collection was designed and implemented by the Nutrient Data Laboratory (USDA). Analyses of eight flavan-3-ols (catechin, catechin gallate, epicatechin, epicatechin gallate, epigallocatechin, epigallocatechin gallate, gallocatechin, and gallocatechin gallate), six anthocyanins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin, and petunidin), two flavanones (hesperetin and naringenin), two flavones (apigenin and luteolin), and two flavonols (myricetin and quercetin) were performed by the Food Composition Laboratory (USDA) using a hydrolysis method for the anthocyanidins, flavones, and flavonols and a direct extraction method for the flavan-3-ols and flavanones. Experimental results compare favorably (few statistically significant differences) to literature values in the flavonoid and proanthocyanidin database previously compiled by the Nutrient Data Laboratory. The results of this study showed a seasonal variation only for blueberries. This study also showed that the variation in the flavonoid content of foods, as purchased by the U.S. consumer, is very large. The relative standard deviation, averaged for each flavonoid in each food, was 168%.
Non-melanoma skin cancer is the most common malignancy in humans and is equivalent to the incidence of malignancies in all other organs combined in the United States. Current methods of prevention depend on sunscreens in humans, efficacy of which is largely undetermined for non-melanoma skin cancers. Green tea polyphenols have the greatest effect with respect to chemoprevention and have been found to be most potent at suppressing the carcinogenic activity of UV radiation. They protect against many of the other damaging effects of UV radiation such as UV-induced sunburn response, UV-induced immunosuppression and photoaging of the skin. They exert their photoprotective effects by various cellular, molecular and biochemical mechanisms in in vitro and in vivo systems. Green tea polyphenols thus have the potential, when used in conjunction with traditional sunscreens, to further protect the skin against the adverse effects of ultraviolet radiation.
Tea constituents, including polyphenols, are hypothesized to have chemopreventive properties, and inhibit the induction of skin cancers in animal models.
To explore the association between regular tea consumption (>or=1 cup/d for >or=1 month) and the incidence of squamous cell (SCC) and basal cell (BCC) carcinomas.
A population-based case-control study of 770 individuals with BCC, 696 with SCC, and 715 age- and sex-matched control subjects.
After adjustment for age, sex, and lifetime history of painful sunburns, ever having consumed tea regularly was associated with a significantly lower risk of SCC (odds ratio [OR] = 0.70; 95% confidence interval [CI] 0.53-0.92), especially among long-term drinkers (>or=47 years consumption: SCC, OR = 0.49; 95% CI 0.29-0.83; P for trend = .008) and among those consuming >or=2 cups/d (OR = 0.65; 95% CI 0.44-0.96; P for trend = 0.013). After adjustment for age and sex, ever having consumed tea regularly was weakly associated with BCC risk (OR = 0.79; 95% CI 0.63-0.98).
Our case-control study was susceptible to recall bias and to confounding by unknown cancer risk factors associated with tea consumption.
Our findings support the existence of an inverse association between tea consumption and skin carcinogenesis.
A single-dose ingestion of flavanol-rich cocoa acutely reverses endothelial dysfunction. To investigate the time course of endothelial function during daily consumption of high-flavanol cocoa, we determined flow-mediated dilation (FMD) acutely (for up to 6 hours after single-dose ingestion) and chronically (administration for 7 days). The study population represented individuals with smoking-related endothelial dysfunction; in addition to FMD, plasma nitrite and nitrate were measured. The daily consumption of a flavanol-rich cocoa drink (3 x 306 mg flavanols/d) over 7 days (n=6) resulted in continual FMD increases at baseline (after overnight fast and before flavanol ingestion) and in sustained FMD augmentation at 2 hours after ingestion. Fasted FMD responses increased from 3.7 +/- 0.4% on day 1 to 5.2 +/- 0.6%, 6.1 +/- 0.6%, and 6.6 +/- 0.5% (each P < 0.05) on days 3, 5, and 8, respectively. FMD returned to 3.3 +/- 0.3% after a washout week of cocoa-free diet (day 15). Increases observed in circulating nitrite, but not in circulating nitrate, paralleled the observed FMD augmentations. The acute, single-dose consumption of cocoa drinks with 28 to 918 mg of flavanols led to dose-dependent increases in FMD and nitrite, with a maximal FMD at 2 hours after consumption. The dose to achieve a half-maximal FMD response was 616 mg (n=6). Generally applied biomarkers for oxidative stress (plasma, MDA, TEAC) and antioxidant status (plasma ascorbate, urate) remained unaffected by cocoa flavanol ingestion. The daily consumption of flavanol-rich cocoa has the potential to reverse endothelial dysfunction in a sustained and dose-dependent manner.
The dietary flavan-3-ol (-)-epicatechin improves the bioactivity of nitric oxide in arterial vessels in vivo. Moreover, it effectively protects cultured vascular endothelial cells from signs of oxidative stress and elevates intracellular nitric oxide in vitro. We addressed the effects of (-)-epicatechin, its metabolic conversion products and structurally related compounds on NADPH oxidase activity in intact human umbilical vein endothelial cells (HUVEC) and in cell lysates. (-)-Epicatechin proved to be an O2*(-)-scavenger but did not inhibit NADPH oxidase activity, whereas the converse pattern was observed for the metabolites 3'- and 4'-O-methyl epicatechin. The dimer procyanidin B2 and (-)-epicatechin glucuronide were O2*(-)-scavengers and inhibited NADPH oxidase. Analysis of structure-activity relations with 45 compounds suggests an apocynin-like mode of NADPH oxidase inhibition. Notably, HUVEC converted (-)-epicatechin to NADPH oxidase-inhibitory methyl ethers. These data identify endothelial NADPH oxidase as candidate target of dietary flavonoids and particularly of their metabolites.
Quercetin, a member of the flavonoids family, is one of the most prominent dietary antioxidants. It is ubiquitously present in foods including vegetables, fruit, tea and wine as well as countless food supplements and is claimed to exert beneficial health effects. This includes protection against various diseases such as osteoporosis, certain forms of cancer, pulmonary and cardiovascular diseases but also against aging. Especially the ability of quercetin to scavenge highly reactive species such as peroxynitrite and the hydroxyl radical is suggested to be involved in these possible beneficial health effects. Consequently, numerous studies have been performed to gather scientific evidence for these beneficial health claims as well as data regarding the exact mechanism of action and possible toxicological aspects of this flavonoid. The purpose of this review is to evaluate these studies in order to elucidate the possible health-beneficial effects of the antioxidant quercetin. Firstly, the definitions as well as the most important aspects regarding free radicals, antioxidants and oxidative stress will be discussed as background information. Subsequently, the mechanism by which quercetin may operate as an antioxidant (tested in vitro) as well as the potential use of this antioxidant as a nutraceutical (tested both ex vivo and in vivo) will be discussed.
Endothelial function, nit.ic ox'ide, ariä cocoa flavanols
- C Heiss
- H Schroeter
- J Balzer
- P Kleinbongard
- S Matgin
- H Sies
- M Kelm
Heiss, C., Schroeter, H., Balzer, J., Kleinbongard, P, Matgin,
S., Sies, H., Kelm, M.: Endothelial function, nit.ic ox'ide,
ariä cocoa flavanols. J. Cardiovasc. Pharmacol. 47, S 128-S 135
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