Article

Oral intake of proanthocyanidin-rich extract from grape seeds improves chloasma

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Abstract

Chloasma (melasma), an acquired hypermelanosis, is often recalcitrant to various treatments and an amenable, as well as safe, pigment-reducing modality is needed. We investigated that the reducing effect of proanthocyanidin, a powerful antioxidant, on chloasma in a one-year open design study. Proanthocyanidin-rich grape seed extract (GSE) was orally administered to 12 Japanese woman candidates with chloasma for 6 months between August 2001 and January 2002 and to 11 of these 12 for 5 months between March and July 2002. Clinical observation, L* value (lightening) and melanin index, and size (length and width) measurements of chloasma were performed throughout the study period. The first 6 months of GSE intake improved or slightly improved chloasma in 10 of the 12 women (83%, p < 0.01) and following 5 months of intake improved or slightly improved chloasma in 6 of the 11 candidates (54%, p < 0.01). L* values also increased after GSE intake (57.8 +/- 2.5 at the start vs 59.3 +/- 2.3 at 6 months and 58.7 +/- 2.5 at the end of study). Melanin-index significantly decreased after 6 months of the intake (0.025 +/- 0.005 at the start vs 0.019 +/- 0.004 at 6 months) (p < 0.01), and also decreased at the end of study (0.021 +/- 0.005) (p < 0.05). GSE is effective in reducing the hyperpigmentation of women with chloasma. The beneficial effects of GSE was maximally achieved after 6 months and these was no further improvement after this period. The latter GSE intake for 5 months may prevent chloasma from becoming worse prior to the summer season. GSE is safe and useful for improving chloasma.

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... Therapy remains a challenge for melasma, and topical treatments are the mainstay but may include allergic and contact dermatitis, depigmentation of surrounding normal skin, and postinflammatory hyperpigmentation [4]. Thus, the oral intake of antioxidants such as Vitamin C, E and grape seed extract have recently attracted much attention in the treatment of melasma, with expectation to prevent UV-induced melanogenesis and/or to reduce hyperpigmentation [5][6][7][8]. ...
... It has been reported in 50-70% of pregnant women and in non-pregnant women who are taking birth control pills [5]. Sun exposure together with the endocrine disorders, genetic factors, medications, nutritional deficiency, and hepatic dysfunction are risk factors for melisma [6]. Recently, increasing effort has been devoted to reveal the relationship between food intake and skin condition, which led to the modern concept of "skin care from within" [5,13]. ...
... Recently, increasing effort has been devoted to reveal the relationship between food intake and skin condition, which led to the modern concept of "skin care from within" [5,13]. It has been reported that some nutrients, such as vitamin A, E, C, as well as the herbal extracts, such as pycnogenol, orange extract and grape seeds extract exhibited skin lightening effects due to their antioxidant effects [5,6,14]. In this respect, the importance of the dietary source for photoprotection has attracted a great interest. ...
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The aim of this study was to assess the efficacy of an oral supplement (CP) containing collagen peptide, soy peptide, and chrysanthemum extract in Chinese female adult volunteers with melasma. The approval of the Institutional Ethics Committee of the third affiliated hospital, Sun-Yat Sen University, was obtained before the study. A signed consent was obtained from each volunteer prior to study to enable the volunteer to appreciate the aim of the study and the consequences of her consent. Sixty-two female volunteers aged 30–60 years were included in the study, and were randomized into a treatment group or a placebo group. The skin tone of the pigmented spots was evaluated using Chromameter, and pigment density was evaluated using Mexameter before and after the treatment. Significant changes in skin tone parameters of L value and ITA° (individual typology angle) were detected in the lesion area after the treatment (P < 0.01). When compared with placebo group, the treatment group achieved significant improvement in the brightness of the pigmented spots at the 45 and 60-day time points. A significant decrease in the level of melanin was observed in the treatment group when compared with the placebo group (p < 0.01). All data demonstrated through non-invasive in vivo instrumental measurement that daily oral intake of CP had clinical efficacy of reducing melasma severity.
... 9,10,14 Moreover, cell degradation and UV exposure will lead to a heterogeneous overproduction of melanin by melanocytes, which leads to facial spots and a heterogeneous complexion. 15 As the first line of cell defense against oxidative stress, primary antioxidants correspond to the endogenous system comprised of the only three antioxidant enzymes of the body: superoxide dismutase (SOD), catalase, and glutathione peroxidase. These enzymes contain trace elements in their active sites, such as copper, zinc, and selenium, supplied by food and essential for their enzymatic activity. ...
... 9,10,14 Furthermore, cell degradation and UV exposure results in a heterogeneous overproduction of melanin by melanocytes, which can cause the appearance of facial spots and a heterogeneous complexion. 15 Our results suggest a positive effect of oral supplementation rich in primary and secondary antioxidants on skin radiance. Skin color, facial luminosity, and firmness have been improved and imperfections reduced. ...
... 17 Flavanol monomers and vitamin C are known to reduce the tyrosinase activity necessary for the melanogenesis and, thus, they are able to regulate the melanin synthesis. 15,[45][46][47] The term "radiance" often refers to the shining and lightening aspect. Interestingly, in our study, luminosity, linking with the global skin color and skin homogeneity, was improved. ...
Article
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Background: Environmental factors impact the skin aging resulting in decrease of skin radiance. Nutrition and particularly antioxidants could help to fight against skin degradation. Objective: The aim of this study was to evaluate the effects of an oral supplement rich in specific antioxidants, SkinAx(2TM), on the improvement of the skin radiance in women. Methods: The open-label clinical study enrolled 35 women, aged 40-70, with facial dull complexion. Subjects were supplemented orally with a daily dosage of 150 mg of an antioxidant-rich formulation containing superoxide dismutase-rich melon concentrate, grape seed extract rich in monomers of flavanols, vitamin C, and zinc for 8 weeks. Each subject served as her own control. The C.L.B.T.(™) test has been used to evaluate facial skin coloring (C), luminosity (L), brightness (B), and transparency (T) involved in skin radiance. Facial skin imperfections have been assessed by clinical assessment. Firmness has been evaluated by clinical assessment and cutometer measurement. Finally, an auto-questionnaire has been carried out in order to evaluate the satisfaction of the subjects concerning different parameters involved in skin radiance and the global efficacy of the supplement. Results: Skin "red pink" and "olive" colors were significantly improved after supplementation (P<0.0001). Luminosity was increased by 25.9% (P<0.0001) whereas brightness and transparency were not affected by the supplementation. Facial skin imperfections were significantly reduced after the antioxidant-rich formulation intake (global reduction: -18.0%; P<0.0001). Indeed, dark circles, redness, and spots significantly diminished after oral treatment. Firmness and elasticity have been shown to be improved. Subjects were globally satisfied by the product (82.4%) and have found improvements on their facial skin. Furthermore, 64.7% reported to look better at the end of the supplementation. Conclusion: The oral supplement containing the antioxidant-rich formulation was found to improve skin radiance by reducing skin coloring, increasing face luminosity, reducing imperfections, and improving skin firmness in women with dull complexion.
... Careful screening for personal and familial risk factors for thromboembolism is recommended before initiation. [22] The drug is Table 1: Systemic agents being currently used for treatment of melasma and their routes of administration [5,[7][8][9][10][11][12] Name of systemic agent Routes of administration (as reported till date) Oral Miscellaneous agents (hyaluronic acid, green tea, ellagic acid-rich pomegranate extract and coumarin extracts from the plant Angelica dahurica, epidermal growth factor and combinations of multiple natural extracts namely natural collagen extracts, bearberry extract, Glycyrrhiza glabra extract, grape seed extract, lycopene, kelp, olive leaf extract, hawthorn, jujube, sea buckthorn, starch, coix seed, pearl extracts, etc.) • Blocking the conversion of plasminogen to plasmin in keratinocytes and epidermal basal cells by plasminogen activator by reversibly blocking the lysine binding sites on plasminogen. • Reducing the level of basic fibroblast growth factor (a potent growth factor of melanocytes). ...
... [8] Yamakoshi et al. demonstrated the skin-lightening property of proanthocyanidin-rich grape seed extract in the treatment of melasma on Japanese women. [11] Thus, most of these agents are used as over-the-counter adjuncts without much credible scientific evidence. ...
... Grape seed extract Grape seed extract contain an antioxidant proanthocyanidin (94). Oral intake of grape seed (Table 3) extract for 6 months resulted in lightening effects of melasma (94). ...
... Grape seed extract Grape seed extract contain an antioxidant proanthocyanidin (94). Oral intake of grape seed (Table 3) extract for 6 months resulted in lightening effects of melasma (94). There is however dearth of data regarding its efficacy on topical use. ...
Article
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A blemish free, even-toned skin is universally associated with healthy skin. This reasoning makes people desire to have a flawless skin. Melanin is a naturally occurring pigment in humans. This pigment is responsible for skin, hair, and eye color, therefore determines our race and phenotypic appearance. On darker skin types, it is common that melanin production processes malfunctions. These malfunctions often lead to overproduction and secretion of melanin. As a result, unwanted pigmentary problems such melasma occur. Due to unknown etiology and its recurrence in nature, melasma is challenging to treat. The current available melasma treatment options often produce undesired side effects and suboptimum results. First-line topical treatments usually involve hydroquinone or topical steroids. Apart from the irritant reactions, this treatment mode is not suitable for all skin types. Skin care specialists are in search of an effective long-term cosmetics and cosmeceuticals to address hypermelanosis problems. Understanding of naturally occurring depigmenting agents provides an opportunity for more effective ways to manage melasma in all skin types. This review considers the benefits of naturally occurring ingredients which could help address skin pigmentation problems and broaden the choice for skin-lightening treatments.
... Ultraviolet (UV) radiation is the major factor in the etiopathogenesis of melasma. Additionally, it has been found that reactive oxygen species (ROS) generated by UV can accelerate skin pigmentation [1][2][3] . There are a lot of treatment alternatives for melasma. ...
... There are a lot of treatment alternatives for melasma. Antioxidants, ROS scavengers and inhibitors of ROS production have been used in the treatment of melasma for the prevention of UV-induced melanogenesis 1,[3][4][5][6][7] . However, there has been no study on the antioxidant activity (AOA) of patients with melasma. ...
Article
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Background and Design: Melasma is a common, symmetric hypermelanosis characterized by irregular brown to gray-brown macules on the face. It is frequently associated with pregnancy and oral contraceptive consumption. Sunlight and genetic factors play major roles in the pathogenesis of melasma. Human skin exposed to ultraviolet light or environmental oxidizing pollutants become a preferred target of oxidative stress. Topical and oral antioxidants are used to treat melasma. To investigate serum antioxidant capacity in patients with melasma and relationship between antioxidant levels and melasma severity. Materials and Methods: Forty-nine cases of melasma and 35 controls were included in the study. Each patient’s skin pigmentation was assessed using the Melasma Area Severity Index (MASI) and mexameter reading. Serum trolox equivalent antioxidant capacity (TEAC), total antioxidant activity (TAOA), and ferric reducing power (FRAP) were evaluated in patients and controls by spectrophotometric method. Results: TEAC levels were higher in patients than in controls (p
... However, Shoji et al. (2005) found no correlation between the degree of procyanidin polymerization and its tyrosinase inhibitory potential. Extracts EPA (2004) rich in procyanidins such as grape seed extract (Yamakoshi et al., 2004(Yamakoshi et al., , 2003 and French maritime pine (Pinus pinaster) bark extract (Ayres et al., 2015;D'Andrea, 2010) have also shown a skin whitening property. ...
Article
Hyperpigmentation is one of the most common skin disorder that affects both men and women of all ethnic groups, caused by several factors, such as UV exposure and skin inflammation. Topical whitening agents were found to be the best and the least aggressive therapy for treating hyperpigmentation compared to instrumental approaches. However, topical treatment faces several obstacles due to the low stability of the whitening agents. Therefore, the encapsulation of these agents was found to be crucial as it enhances their physicochemical stability and increases their concentration at the targeted site via an improved skin permeation, penetration or distribution. In this article, we review the literature aimed to enhance the stability and the targeting of skin whitening agents through their encapsulation in various nano and micro-particulate systems.
... The methanol extract of dried Morus alba leaves and its active compound Mulberroside F (moracin M-6,3′-di-O-β -D-glucopyranoside) also showed inhibition of tyrosinase, and inhibited melanin formation of melan -a cells, this indicated mulberroside F might be used as a skin whiten-ing agent [44,45]. Yamakoshi et al. [46] investigated the lightening effect of proanthocyanidin---rich grape seed extract (GSE) by oral administration of GSE in guinea pigs model. Histological evaluation of guinea pigs skin also showed a decrease in the number of 3,4---dihydroxyphenylalanine (DOPA)---positive melanocytes, which suggested that oral administration of GSE is effective in lightening agent and may be related to the inhibition of melanin synthesis by tyrosinase in melanocytes. ...
Article
Cutaneous pigmentation plays critical role in determining the color of skin along with photo protection of skin from dreadful effects of ultraviolet radiations. Conversely, abnormal accumulation of melanin is responsible for hyper pigmentary disorders such as melasma, senile lentigines and freckles. Because of the visible nature of dermatologic diseases, they have a considerable psychosomatic effect on affected patients. Tyrosinase inhibitors are molecules that interrelate in some way with the enzyme to prevent it from working in the normal manner. Past many decades witnessed the quest for the development of natural tyrosinase inhibitors due to imperative role played by tyrosinase in the process of melanogenesis and fungi or fruit enzymatic browning. Mechanism of pigmentation is characterized by the intact process of the synthesis of specialized black pigment within melanosomes. Melanin is synthesized by a cascade of enzymatic and chemical reactions. For this reason, melanin production is mainly controlled by the expression and activation of tyrosinase. In the current article, we discussed tyrosinase inhibitors from the natural sources, which can be an essential constituent of cosmetics products and depigmenting agents for the treatment of hyperpigmentory disorders.
... It has been evidenced that antioxidants and ROS scavenger products such as proanthocyanidin-rich GSE formulation are able to decrease melanin biosynthesis and UV-induced hyperpigmentation in animal models [79]. Improvement of facial hyperpigmentation of women with chloasma was recorded following oral administration of proanthocyanidin rich GSE for 12 months without any adverse effect [80]. ...
Article
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The grape seed extract (GSE) and its main active polyphenol, resveratrol (RES), have shown considerable antioxidant activities, besides possessed protective and therapeutic effects against various skin complications. This paper discusses the favorable effects of RES, GSE and their nanoformulations for dermatological approaches, with specific emphasis on clinical interventions. In this manner, electronic databases including PubMed, Science Direct and Google Scholar were searched. Data were collected from 1980 up to February 2019. The search terms included “Vitis vinifera”, “grape”, “resveratrol”, “skin”, “dermatology”, and “nanoformulation”. To increase the skin permeability of GSE and RES, several innovative nanoformulation such as liposomes, niosomes, solid–lipid nanoparticles, nanostructured lipid carriers, and lipid-core nanocapsule has been evaluated. According to our extensive searches, both RES and GSE have beneficial impacts on skin disorders such as chloasma, acne vulgaris, skin aging, as well as wound and facial redness. More clinical studies with nanoformulation approaches are recommended to achieve conclusive outcomes regarding the efficacy of RES and GSE in the management of skin diseases.
... Several studied showed that distillate of Pinus pinaster is rich in epicatechin, catechin, ferulic acid and caffeic and procyanidins thus proved as nutricosmetics in reducing melisma [140] and UV-linked damage [172]. While in another study, oral administration of extract from grape seed enriched with procyanidins showed reduction of hyperpigmentation in women suffering from melisma [210]. Similarly, the oral administration of epicatechin and catechin, cocoa flavonols showed photoprotective influences [74]. ...
Chapter
Antioxidants are able to scavenge free radicals that cause degradation of food, pharmaceutical and cosmetic products during processing and storage. Natural ingredients in food products are everywhere continually gaining popularity, and the use of plant extracts in cosmetic formulations are on the rise. Additionally, chemists, pharmacists and nutritionists are focusing on the development of new nutritional applications that target not only to disease prevention but also in improving skin health, appearance of the food product and overcoming any off flavors. This approach is the beginning of the new era where the products intended to promote well-being and health will be available to meet the consumers’ demands. Polyphenols are the most abundant natural antioxidants in nature commonly found in both edible and non-edible parts of plants, and they have been reported to have multiple biological effects, including antioxidant, antimicrobial, anti-viral, anti-inflammatory, analgesic and antipyretic activities. The extraction of polyphenols from plant sources has drawn increasing attention as a low-value source of antioxidants. Although the development in analytical techniques has played a significant role in the detection of a wide range of polyphenols, success still depends on the method of extraction. In literature, several combinations of solvent, temperature, extraction time and agitation speed have been presented in order to achieve maximum phenolic yields, but these conventional proposals are considered as burden on the environment due to the use of high temperatures for long periods of time and secondly due to the effect on the heat-sensitive components of polyphenols. Alternatively, the application of novel techniques such as ultrasound, pulsed electrical field, high-pressure CO2 and others is more welcoming due to their reduced usage of organic solvents, low operational temperatures, short processing times and better quality and yields with high selectivity toward targeted compounds. The extracts rich in phenolic compounds are attractive ingredients for food, cosmetics and pharmaceutical products due to their beneficial biological properties importantly their antioxidant potential. This chapter is aimed at discussing the extraction of polyphenols using environment-friendly techniques and to use these polyphenol-rich extracts in various food, cosmetic and pharmaceutical products.
... 107 Five volunteers were reported to be moderately irritated with formulation andwere advised to use cream containing betamethasone (counter irritant) twice aday on effected part of skin under trial. Volunteers were 42 instructed, not to use any other skin product, especially whitening agents throughout the duration of study (12-weeks). ...
... Proanthocyanidin extracted from grape seeds has significant antioxidant action and has been shown to be beneficial in melasma in several studies. 52,53 In a study of women with melasma, proanthocyanidin administered orally for 6 months resulted in significant skin-lightening in 10 of the 12 women (83%, P < 0.01). 53 Acidified amino acid peels (topical) Topical acidified amino acid peels with a pH similar to that of skin have significant antioxidant and tyrosinase inhibitory action and have fewer SEs as compared with glycolic acid. ...
Article
Full-text available
Melasma is a common, acquired, symmetrical hypermelanosis. It negatively impacts the patient's quality of life and responds poorly to treatment. Although earlier classified as epidermal and dermal, melasma is now thought to be a complex interaction between epidermal melanocytes, keratinocytes, dermal fibroblasts, mast cells, and vascular endothelial cells. Factors influencing melasma may include inflammation, reactive oxygen species, ultraviolet radiation, genetic factors, and hormones. With a better understanding of the pathogenesis of melasma and the realization that targeting melanin synthesis alone is not very effective, treatments focussing on newly implicated factors have been developed. These include agents targeting hyperactive melanocytes, melanosomal transfer to keratinocytes, defective skin barrier, the mast cells, vasculature, and estrogen receptors as well as drugs with anti-inflammatory and antioxidant activity. Many of these newer agents are botanicals with multimodal mechanisms of action that offer a better safety profile when compared with the conventional drugs. There has also been a focus on oral agents such as tranexamic acid, flutamide, and ascorbic acid. It has been suggested that the "triple therapy of the future" may be a combination of hydroquinone, an antiestrogen and a vascular endothelial growth factor inhibitor, as the "ideal" skin-lightening agent.
... Grape seed extract (GSE) is also rich in proanthocyanins. In a 1-year study of Japanese women with chloasma, oral administration of 67 mg of GSE 3 times a day effectively decreased hyperpigmentation, and the extract was shown to be safe and well-tolerated [34]. ...
Article
Full-text available
Introduction Skin exposure to ultraviolet radiation (UVR) can cause oxidative stress, particularly in the absence of adequate protective measures or in individuals with a sensitive skin type. Most commonly, protection from UVR entails the use of topical sunscreens. Sunscreens, however, have various limitations. The objective of this study was to evaluate the efficacy and tolerability of an oral food supplement containing a combination of actives with mainly antioxidative properties (vitamins A, C, D3, E, selenium, lycopene, lutein, as well as green tea, polypodium and grape extracts) in the context of photoprotection. Methods Photoprotective efficacy was assessed in a 12-week-long, open, prospective and monocentric clinical study with 30 subjects (27 women and 3 men) having a Fitzpatrick skin type I-III and manifesting clinical ageing signs. The study included several visits (14, 28, 56, and 84 days after starting supplement intake), in which photoprotection was evaluated by the measurement of the minimal erythema dose (MED), while the antioxidant capacity of the skin was assessed through ferric reducing antioxidant power (FRAP) and malondialdehyde (MDA) assays. Additionally, several skin parameters (including radiance, elasticity, and moisture) were evaluated. Product evaluation was performed throughout the length of the study by means of a self-assessment questionnaire, and safety was monitored through a self-recording of all observed adverse reactions. Results The MED levels increased significantly compared to baseline throughout the study visits, reaching an increase of + 8.1% at T84, p < 0.001. FRAP results also indicated a significant increase in the antioxidant capacity of the skin compared to baseline (+ 22.7% at T84, p < 0.001), while the MDA assay showed a significant decrease in MDA concentration compared to baseline (− 6.4% at T84, p < 0.001) which, in line with the FRAP results, indicated enhanced antioxidative protection of the skin. All assessed skin parameters, including radiance (+ 36.1% at T84, p < 0.001), gross elasticity (+ 13.2% at T84, p < 0.001), net elasticity (+ 28.0% at T84, p < 0.001), and moisture (+ 13.8% at T84, p < 0.001) were also significantly improved. The product was well tolerated as no adverse events were attributed by the investigators to the use of the product. Additionally, the global score obtained from the self-assessment questionnaires provided overwhelmingly positive feedback from the study subjects. Conclusions The food supplement evaluated in this study was effective and well-tolerated by the subjects, demonstrating a beneficial effect in terms of photoprotection, enhancing the antioxidative status of the skin and improving general skin condition. Trial Registration Retrospectively registered 3rd October 2019, ISRCTN18121679.
... Proanthocyanidin (PA) is a polyphenolic compound and has been reported to have anti-cancer (12) and cardioprotective effects (13) , to protect against ulcers and gastric mucosal injury (14) , to have a protective effect against diabetic retinopathy in streptozotocin-induced diabetic rats (15), to ameliorate diabetic macrovascular complications [16] and to protect against cisplatin-induced nephrotoxicity (17) . However, the underlying protective mechanisms of PA against diabetic nephropathy have not been fully delineated. ...
... This property makes them highly valuable for applications in cosmetic and food industry; for example, as supplements, food preservatives and natural colourants (Ignat et al., 2011). In particular, polyphenols provide a skin protection that prevents ageing and other skin conditions (Yamakoshi et al., 2004). For instance, Wittenauer, et al. (2015) drawback to overcome is the bulky equipment and the long extraction times. ...
Article
Microwave assisted extraction advantages are widely recognised. However, its implementation at industrial scale is restricted due to microwave limitations. In this work, a microwave pretreatment is proposed as an easy scale-up alternative for grape pomace polyphenol extraction, especially for anthocyanins. The double effect of this pretreatment on extraction yield and on product richness is assessed. Microwaves accelerate the extraction kinetics of most compounds, but their effect on polyphenols is more pronounced than in other substances (like sugars and fibres). These differentiated rates are exploited to improve the polyphenol richness of the final dry product. By selecting the appropriate operating conditions, polyphenol yield was increased by 57% and, simultaneously, dry product richness was enhanced by 32%. Also, anthocyanin extraction boost was remarkable. Its content in the final dry product was 85% higher than the one obtained without the microwave pretreatment. The cellular bioactivity of these extracts was improved by 83% and 133%.
... Grape seed extract (GSE) is also rich in proanthocyanidins. In a one-year study of Japanese women with chloasma, oral administration of 67 mg of GSE three times a day effectively reduced the hyperpigmentation and the extract was shown to be safe and well tolerated [13]. ...
Article
Full-text available
Background: Melasma is a common hyperpigmentation disorder, characterized by light-to-dark brown patches, usually distributed on sun-exposed areas of the body. The objective of this study was to evaluate the efficacy and tolerability of an oral nutritional supplement containing Pinus pinaster and Grape seed extract, vitamins and minerals, used concomitantly with a high SPF sunscreen in 30 women with mild-to-moderate facial melasma. Methods: Efficacy was assessed by measurement of the Melasma Area and Severity Index (MASI), instrumental analysis of the lesions (Mexameter ® , VISIA ®)) and Patient's and Physician's Global Assessment (PGA). Results: The MASI score decreased significantly compared with baseline at days 28, 56, and 84. Mexameter ® analysis showed a significant decrease of ∆M (difference in the melanin index between melasma and adjacent area). VISIA ® results also showed a reduction in the number and areas of UV pigmented spots and in the areas of melasma overtime. Both the Patient's and Physician's Global Assessment showed that the product led to an improvement of the lesions in terms of depigmentation and had positive cosmetic features without adverse events. Conclusion: The oral supplement subject of this study in combination with high SPF sunscreen was effective and well-tolerated for treatment of mild to moderate facial melasma.
... Several studied showed that distillate of Pinus pinaster is rich in epicatechin, catechin, ferulic acid and caffeic and procyanidins thus proved as nutricosmetics in reducing melisma [140] and UV-linked damage [172]. While in another study, oral administration of extract from grape seed enriched with procyanidins showed reduction of hyperpigmentation in women suffering from melisma [210]. Similarly, the oral administration of epicatechin and catechin, cocoa flavonols showed photoprotective influences [74]. ...
... Cha, et al. evaluated the effect of 43 marine algae extracts on melanin synthesis and located that few extracts evidenced potent tyrosinase inhibitory activity almost like that of positive control, kojic acid without causing any side effects. 52 Hence, these extracts are often used as an ingredient in skin lightening cosmeceuticals. ...
Article
Full-text available
Skin whitening is a term used for lightening the complexion of the skin through artificial means like creams, lotions, soaps and injections. Unfortunately, the appeal of these skin bleaching products is based on the obsession of people across the world with skin color. Melanins are produced by specialized cells, termed melanocytes, which are located primarily in the skin, hair bulbs, and eyes. The melanins can be of two basic types: eumelanin’s, which are brown or black, and phaeomelanin’s, which are red or yellow, in mammals typically there are mixtures of both types Increased production and accumulation of melanins characterize number of skin diseases, which include hyperpigmentation such as melanoma, post-inflammatory melanoderma, solar lentigo, etc. Several modalities of treatment for these problems are available including chemical agents or physical therapies. The aim of this review article is to show that some of the skin whitening creams, often sold illegally without a prescription may contain dangerous ingredients that could put people health at risk
... Proanthocyanidin is a powerful antioxidant, extracted from grape seed [38]. Studies have shown the efficacy of oral proanthocyanidin in treating melasma [83,84]. ...
... 17 Later, a one-year study in 12 Japanese women in the age 34-58 years with chloasma (melasma) showed that oral administration of proanthocyanidin-rich GSE (162 mg of proanthocyanidin/day) significantly increased L*, decreased melanin index, and overall improved abnormal facial pigmentation as early as 6 months. An apparent lightening effect of absorbed oligomeric procyanidins and monomeric flavanols, for example, (+)-catechin and (-)-epicatechinwas not only through direct inhibition of melanin synthesis in melanocytes but also through the scavenged UV-induced ROS facilitating melanocyte proliferation.18 However, in our study, a reduced melanogenesis is most likely not due to GSE alone, as the base with GSE showed less significant results in improving skin pigmentation compared with sunscreen with GSE and benchmark sunscreen containing ginger extract (according to the ingredients list on a label). ...
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.
... Lee et al. [79] have reported that mulberroside F, the active component of dried mulberry (Morus alba) leaves also showed inhibitory effects on tyrosinase activity and on melanin formation in melan-a cells. This compound also exhibited superoxide scavenging activity that is involved in the protection against auto-oxidation [80], suggesting a role for M. alba as a component of lightening cosmetics. ...
Article
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Skin pigmentation is an important human phenotypic trait that gives special aesthetic hue to individuals and also protective covering against solar ultra violet radiations, but excessive pigment production and uneven distribution, appear as serious undesirable hyperpigmentory anomalies. To overcome this, various therapeutic agents and skin-lightening cosmetics are in big demand across Asia, and the quest for fairness has led to identification of many new ingredients. The mechanisms underlying pigmentation has been researched extensively and the knowledge are being updated regularly. To understand the etiology of normal and uneven skin pigmentation, first part of the review serves us basic updated information regarding the normal process of melanogenesis and strict coherent attributes that monitor the skin pigmentation control machinery. While the later part of the review focuses on some abnormal hyperpigmentory anomalies, their mode of action at the cellular level and various approaches that exploit the natural botanicals for their permanent and cost effective treatment.
... In fact, this pigment's biosynthesis plays a crucial role in skin protection by shielding it from sunlight damage (UV radiation absorption) and ion accumulation, as well as by reactive oxygen species (ROS) trapping [45][46][47][48]. Oxidative stress, a direct consequence of the environment (UV radiation, pollution, etc.) and human lifestyle (cigarette smoking, etc.), is implied in skin pathogenesis and leads to alterations in connective tissues and to the formation of lipid peroxides and ROS harmful to the skin, hence leading to accelerated ageing [49][50][51][52]. ...
Article
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With the public’s growing interest in skin whitening, lightening ingredients only used under dermatological supervision until recently, are more and more frequently incorporated into cosmetic formulas. The active agents that lighten skin tone are either natural or synthetic substances, and may act at various levels of melanogenesis. They are used to treat various skin pigmentation disorders or simply to obtain a lighter skin tone as whiter skin may be synonymous of wealth, health, youth, and/or beauty in different cultures. However, recent studies demonstrated the adverse effects of some of these ingredients, leading to their interdiction or restricted use under the European Directive and several other international regulations. After an overview of skin whitening practices and the associated risks, this article provides insight into the mechanisms involved in melanin synthesis and the biological assays available to attest the lightening activity of individual ingredients. The legislation dealing with the use of skin lighteners is then discussed. As traditional depigmenting agents such as hydroquinone and corticosteroids are of safety concern, the potential of natural extracts has been investigated more and more; finally, a synthesis of three years of research in our laboratory for such plant extracts will be given.
... Lycopene present in tomatoes and red carrots is also a strong antioxidant. [34] Coenzyme Q10, idebenone, Vitamin C, ferulic acid, and glutathione are some oral and topical antioxidants. Ferulic acid when combined with Vitamins C and E gives a 4-fold increase in photoprotection. ...
Article
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A cosmetic is “intended to be rubbed, poured, sprinkled, or sprayed on, introduced into, or otherwise applied to the human body for cleansing, beautifying, promoting attractiveness, or altering the appearance” while a drug is “intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease, i.e. it affects the structure and function of the body.” Cosmeceuticals attempt to interface between a pure cosmetic and a drug. ey are those which lie between a prescription and a non-prescription over-the-counter product. ey are medical products, which are cosmetics, with functional benefits for the skin, hair, and nails. Cosmeceuticals are disease-treating and disease-modifying. Dermatologists form a unique interface between products with perceived advantages and those with proven efficacy. In an attempt to hard-sell products with minimal side effects, certain compounds may contain sub-therapeutic doses of topical agents hence rendering them ineffective. On the other hand, certain products may form a useful bridge with a safety profile better than cosmetics in their class. is article reviews commonly available and evolving cosmeceuticals, their rationale, side effects, and use in dermatology practice with the aim to sensitize dermatologists about their perceived usefulness.
... After the first phase of treatment, 83% of the participants experienced reductions in melasma intensity (lightening of dark spots), with 54% experiencing continued improvement through the later 5-month treatment phase. L* values (lightening) significantly increased throughout the trial, with a corresponding significant decline in melanin index [60]. Sun exposure is a major factor in melasma. ...
... L* values also increased after GSEP intake (57.8 ± 2.5 at the start vs. 59.3 ± 2.3 at 6 months and 58.7 ± 2.5 at the end of the study). Melanin index significantly decreased after 6 months of the intake (0.025 ± 0.005 at the start vs. 0.019 ± 0.004 at 6 months; p < 0.01), and also decreased at the end of study (0.021 ± 0.005; p < 0.05) [38]. Another study on the effect of proanthocyanidin for melasma has been reported. ...
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Middle-aged and elderly women are affected by various symptoms and diseases induced by estrogen deficiency. Proanthocyanidins, widely present in many kinds of fruits and berries, have many beneficial effects, such as antioxidative, anti-inflammatory, and antimicrobial activities. We researched the effects of proanthocyanidins for middle-aged and elderly women, finding that it has been revealed in many clinical trials and cohort studies that proanthocyanidins contribute to the prevention of cardiovascular disease, hypertension, obesity, cancer, osteoporosis, and urinary tract infection, as well as the improvement of menopausal symptoms, renal function, and skin damage. Thus, proanthocyanidins can be considered one of the potent representatives of complementary alternative therapy.
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The term “cosmeceuticals”, suggested by Kligman more than 20 years ago, refers to topical products that lie in a gray zone where they are viewed as having both pharmaceutical and cosmetic properties [1]. Although the neologism was innovative and relevant, it was rejected from the US Food, Drug, and Cosmetic Act that, according to the 1938s US Congress, labels as drug every substance for use in the diagnosis, cure, treatment or prevention of disease, and as cosmetic any product intended for beautifying and promoting attractiveness. In spite of this, the term cosmeceuticals has recently been gaining increasing popularity, as the term cosmetic seems to be restrictive for those substances that have druglike beneficial effects. On the other hand, the “cosmeceuticals” concept has caused a lot of confusion, because of similar neologisms such as neutraceuticals and/or neoceuticals. Actually, in USA and Canada, most cosmeceuticals are regulated as over the counter (OTC) products, while in Europe they are considered as cosmetics. Only in Japan, a new class of products, called quasi-drugs, has been created [2].
Article
A clinical study was conducted to assess the safety and tolerability of oral doses of proanthocyanidin-rich grape seed extract (GSE) in healthy Japanese adult volunteers. In an open-label, 4-week toxicity test, 29 subjects daily received 1,000, 1,500, or 2,500 mg GSE orally. Serum Fe levels of two subjects in the 2,500 mg GSE group decreased to 61 and 60 μg/100 mL from 205 and 182 μg/100 mL at baseline respectively, at second week of GSE consumption; these values are low but within the normal range for the Japanese population. Two weeks after completing the 4-week course of GSE ingestion, the serum Fe levels of both subjects returned to near baseline levels (210 and 189 μg/100 mL). No subject discontinued the study. Oral intake of GSE up to 2,500 mg for 4 weeks was found to be generally safe and well tolerated in humans. Research with a larger number of subjects is required to confirm these findings.
Chapter
As the largest and outermost organ of the body, human skin is a continual target for chemical toxicity which has the potential to cause tissue damage. In combination with certain chemicals, the presence of additional or existing oxidative stress may exacerbate the degree of damage, due to photoactivation of the chemical. In addition, oxidative-stress per se is a known trigger for cellular pathology. Antioxidants are substances which prevent oxidative damage to cells and tissues. Endogenous enzymatic antioxidants include superoxide dismutase, catalase, glutathione peroxidase; and nonenzymatic antioxidants include vitamins E and vitamin C, coenzyme Q10, glutathione, etc. However, oxidative imbalance will arise when such cellular defences are not able to counteract the rate at which free radicals are generated. An excess of free radicals will cause structural or functional damage to cellular macromolecules leading to perturbations in metabolism, functional impairment, necrosis or apoptosis. In this chapter, we review studies on the use of antioxidants on the skin.
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Research on novel agents from botanicals without the harmful side effects is ongoing and the results are promising. Botanical agents acting as tyrosinase inhibitors include aloe vera extract, rumex occidentalis, and bearberry. Herbal extracts have other actions such as antioxidants, free radical scavengers, and photoprotectants. Some botanicals may have different or several mechanisms of action like melanosome uptake inhibition by keratinocytes and epidermal melanin removal.
Chapter
Post-inflammatory pigment alteration is a common sequela of acne vulgaris in darker skin types (Fitzpatrick skin phototypes IV–VI). Acne-associated dyschromia contributes considerably to the psychological and emotional distress experienced by acne patients and can often be of greater concern to the patient than the acne itself [1–3]. Post-inflammatory hyperpigmentation is seen much more frequently than post-inflammatory hypopigmentation; however, it is important to keep in mind that in addition to acne itself, various acne treatments can cause hyper- or hypopigmentation as a result of irritation.
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There are many options available to choose from in the skin care/cosmetic product arena, with an increasing interest in herbal based products. Since photoaging has multiple cutaneous manifestations, the broad spectrum of multiple mechanisms of action of certain herbal extracts may be promising therapy. Medical providers and skin care professionals are finding that herbal products provide multiple beneficial functionalities with highly reactive molecules and compounds in stable preparations. Products using herbal ingredients must be carefully formulated. Ideally, the finished product is then tested for efficacy and safety. This chapter reviews testing methods and herbal ingredient mechanisms of action. Detailed listings of herbs clinically documented to impact anomalies of photoaging are included, along with a reference list of recent presented or published clinical trials of herbal products. The hope is that skin care providers will make decisions for herbal products to recommend or sell based upon solid scientific evidence.
Article
Background: Melasma causes considerable cosmetic disfigurement and none of the existing treatment modalities are satisfactory. Recently tranexamic acid has been reported to reduce hyperpigmentation in patients with melasma. Objective: The purpose of the study was to evaluate the efficacy and safety of tranexamic acid containing oral medication for the treatment of melasma. Methods: Forty-five female volunteers who had been diagnosed with melasma were enrolled in the present study. Patients were instructed to take medication for 8 weeks. The melanin index (MI) and erythema index (EI) were measured at baseline, and at 4 and 8 weeks. The melasma area and severity index (MASI) was scored at 0, 4, and 8 weeks. Self-satisfaction and safety evaluations were also performed at each visit. Results: The mean MI measured on the lesional skin was decreased at 4 and 8 weeks compared with baseline (p < 0.01 for both). The mean EI measured on the lesional skin and the MASI also showed a significant decrease from baseline to 8 weeks (p< 0.001 for EI and p=0.020 for MASI). Based on self-assessment, 39.5% of the patients were very satisfied, 44.2% were satisfied, and 11.6% felt moderate improvement after 8 weeks of medication; only 2 patients (4.7%) were dissatisfied. Thus, >80% of patients were satisfied with the medication. Adverse effects were minimal and two patients dropped out of the study due to drug-related urticaria and unexpected pregnancy. Conclusion: Tranexamic acid-containing oral medication is an effective and safe therapeutic modality for the treatment of melasma.
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Skin hyperpigmentary disorders are frequent and psychologically disturbing conditions for patients. Skin depigmenting agents have been widely used for the treatment of such disorders. The most efficacious depigmenting agents, such as hydroquinone and the Kligman’s formula, are associated with long-term side effects, and safer skin depigmenting agents, such as kojic acid, arbutin, and niacinamide, might suffer from a significantly lower depigmenting efficacy. Therefore, there is still a need for safe and simultaneously efficacious skin depigmenting compounds. Tranexamic acid and cysteamine are two new and interesting molecules that seem to fulfill the majority of the needed characteristics of an acceptable skin depigmenting agent. In this chapter, a review of most important molecules as well as their side effects will be provided with a focus on the newest skin depigmenting molecules recently emerged into the armamentarium of hyperpigmentation treatments.
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Disorders of hyperpigmentation commonly afflict the ethnic population. Given current immigration trends, dyschromias are poised to become a condition increasingly encountered by clinicians. Developing a strong understanding of treatment options and associated side effects is essential. This chapter will focus on the treatment hierarchy of the most common acquired disorders of hyperpigmentation (i.e., melasma, post-inflammatory hyperpigmentation): (i) topical hypopigmenting agents, (ii) chemical peels, and (iii) oral agents, microdermabrasion, microneedling, and laser therapy. In addition to discussing the advantages and disadvantages of these therapies, it will provide a brief overview of emerging treatment options.
Chapter
Several depigmenting agents are now available both for topical and systemic use with varying degrees of evidence on their efficacy and safety. These agents act by inhibiting melanogenesis, interrupting melanosome transfer, accelerating epidermal desquamation with melanin turnover, antioxidant effects and by other methods. The topical agents that act mainly by inhibiting melanogenesis through tyrosinase inhibition include hydroquinone and derivatives, arbutin, kojic acid, azelaic acid, methimazole, gentisic acid, flavonoids (aloesin, licorice) and antioxidants (ascorbic acid, alpha tocopherols and grapeseed extracts). Examples of agents that interrupt melanosome transfer are niacinamide, soybeans and lectins. Topical agents that accelerate epidermal desquamation and melanin turnover include retinoids, hydroxy acids, salicylic acids and linoleic acids. Other agents that act by varying mechanisms are tranexamic acid, steroids and other active ingredients found in various plant extracts. Topical therapies in combination are found to be more effective as add-on agents to optimise the effects of the other agents and mitigate the side effects of primary agents. They are often used as first-line therapy. The systemic agents used include tranexamic acid, glutathione, oral vitamin C and vitamin E. Some systemic agents such as glutathione are often misused without adequate evidence of its efficacy and long-term safety.
Article
Background Pigmentation of the skin occurs as a result of increased melanin production or deposition due to various reasons including age, hormonal imbalances, endocrine disease, inflammation, and/or exposure to damaging radiation, resulting in dermatologic conditions such as lentigines, melasma, or postinflammatory hyperpigmentation. Although numerous topical therapies exist for skin lightening, they are limited by efficacy and pigmentation recurrence after treatment cessation. New research into systemic therapies for hyperpigmentation has been promising. Objective To summarize the current literature for systemic skin lightening therapies. Methods A review of the literature surrounding systemic skin lightening therapies was completed using PubMed (US National Library of Medicine). Results Multiple systemic therapies for skin lightening exist including oral carotenoids, glutathione, melatonin, Polypodium leucotomos hydrophilic extract, procyanidin, and tranexamic acid. Preliminary data for the treatment of hyperpigmentation are promising, and currently, these oral treatments appear safe. It is not suggested to use intravenous glutathione for skin lightening due to the increased risk of adverse events. Conclusion With the patient population seeking effective systemic treatments for skin pigmentation, it is important for dermatologists to understand the properties, the efficacy, and the adverse events profile of each compound, thus ensuring proper use by patients, and that patients are appropriately counseled regarding treatment expectation and safety.
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Skin disorders have long been associated with nutritional deficiencies that can be due to inadequate intake, abnormal absorption, or improper utilization. Nutrients are the chemical substances found in food, and many of these are essential for life. Nutrients are subdivided into macronutrients (carbohydrates, proteins, and lipids) and micronutrients (vitamins and oligoelements). Although whole, unprocessed foods naturally contain the appropriate balance of nutrients, nutritional supplementation may be necessary to address inflammation and/or a specific nutrient deficiency or excess. Antioxidants are the most important ally for combating free radical and reactive oxygen species (ROS) activity leading to inflammation. Nutrition and wound healing have shown a strong correlation; malnutrition and nutrient deficiencies can have a severe impact on the outcome of traumatic and surgical wounds. Adequate nutrition is necessary for all persons, and enduring adequate water intake is necessary for the perfusion and oxygenation of healthy and healing tissues.
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The use of cosmetic products during pregnancy is one of the times when there is a considerable risk of side effects. The American Food and Drug Administration has classified many pharmacological drugs used in cosmetic applications as category C since their safety profile during pregnancy has not been sufficiently investigated. It should not be suggested to pregnant women or nursing mothers until the safety of all cosmetic agents has been established. To prove the safety of cosmetic applications, further randomized controlled studies are needed. Furthermore, it is critical for female health care providers to be knowledgeable about the use of cosmetic items and applications during pregnancy, to keep up with current research, and to educate pregnant women.
Chapter
Melasma is a common, acquired, symmetrical hypermelanosis, which is often difficult to treat and has a significant negative impact on patients’ quality of life. The most commonly implicated etiological factors include genetic predisposition, ultraviolet radiation (UVR) and hormonal influence. Melasma has been classically described as a linear model and classified on the basis of the presence of localization of melanosomes in the skin as epidermal, dermal, and mixed. However, with the use of newer modalities such as in vivo reflectance confocal microscopy, it has been discovered that the distribution of melanophages is heterogeneous and perhaps, suggests that all melasma is in fact ‘mixed’. Further, changes such as increased solar elastosis and vascular proliferation suggest a significant involvement of the dermis in melasma. Melasma is now being learned as a complex interplay amongst the epidermal melanocytes, keratinocytes, dermal fibroblasts, mast cells, and vascular endothelial cells. The elaboration of this new concept has unlocked several other potential targets for research and treatment in the field of melasma.
Article
Background The skin’s aging process involves a decreased biosynthesis of extracellular matrix proteins (predominantly collagen) compounded by damage from environmental and intrinsic stressors. The Indian population is susceptible to skin damage given its geography and increasing urbanization or a genetic disposition. Previous studies have investigated nutrients such as collagen peptides, vitamins and phytonutrient‐rich botanical extracts for their individual benefits on skin. Aims This study examined the collective effect of a proprietary blend of these nutrients (in Nutrova Collagen+Antioxidants; NCA) on skin parameters, which has not been previously studied, especially in an Indian context. Patients/Methods 34 healthy, Indian women (mean age = 39.5 years) were given a placebo daily for 30 days to establish a baseline, followed by NCA for two intervals of 30 days. 3D image reconstruction allowed the analysis of skin topography and blemishes. Instrumental measurements also included skin firmness, elasticity, hydration, and transepidermal water loss. Clinical evaluation was used to grade blemishes, wrinkles and periorbital hyperpigmentation. Results Based on instrumental evaluation, NCA significantly reduced wrinkle width, open pores, skin roughness, and the colour of hyperpigmented blemishes, while improving skin hydration, firmness and barrier function from baseline to Day 30 and Day 60. NCA also increased elasticity at Day 30. Clinical evaluation showed that periorbital hyperpigmentation and wrinkles reduced significantly. Conclusion NCA is effective for improving overall skin health in Indian women. These results show that targeted nutrient supplementation can improve skin health and further research over extended durations is merited.
Article
Melasma, a common cause for seeking dermatologic care, is a chronic condition of skin hyperpigmentation. With a poorly understood pathogenesis, and no universal cure, melasma is a challenge for many dermatologists. For decades, there has been investigation into the role of oxidative stress in melasma. In this literature review, we introduce the role of oxidative stress in melasma and discuss the function of various topical and oral antioxidant therapies for patients suffering from melasma. Numerous studies have shown efficacy of various antioxidant therapies for treatment of hyperpigmentation, and in this review, we focus primarily on those with less widespread use. Vitamin E, niacinamide, polypodium leucotomos, pycnogenol, grape seed extract, amino fruit acids, phytic acid, zinc, silymarin, Korean red ginseng powder, plant extracts, and parsley all have well‐demonstrated evidence of antioxidant properties, and these substances have been studied in the context of skin hyperpigmentation. Although there is conflicting evidence of their therapeutic efficacy, the use of these naturally occurring substances is promising for patients and medical providers seeking alternative therapeutic options.
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Introduction: Vitiligo is disfiguring and devastating condition to make the general look of humans stigmatic and devalued. Melasma is a general condition of hyperpigmentation and particularly involves the face. The pigmentation disorders of vitiligo (hypopigmentation or de-pigmentation) and melasma (Hypermelanosis) are common among the world's population (around 1% for vitiligo).
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Introduction: Vitiligo is disfiguring and devastating condition that can humans feel stigmatic and devalued. Melasma is a general condition of hyperpigmentation particularly involving the face. The pigmentation disorders of vitiligo (hypopigmentation or de-pigmentation) and melasma (Hypermelanosis) are common among the world's population (around 1% for vitiligo). Objective: The identification of medicinal plants used in the treatment of vitiligo and hypermelanosis. A systematic literature review on harms associated with the medicinal plants used in the treatment of vitiligo and hypermelanosis. To review and summarize information on reported adverse drug reactions (ADRs) associated with these medicinal plants contained in (where access is available) national and global individual case safety report databases. Methods: A systematic review of the literature with special reference to all types of clinical trial and case reports using biomedical databases including Medline, EMBASE, Scopus, International Pharmaceutical Abstracts and so forth to identify medicinal plants alone or as an adjuvant with other treatments and their safety/tolerability in the treatment of vitiligo and Hypermelanosis. Other sources of this search were medicinal plants text books, pharmacopoeias and authentic websites discussing possible treatments for vitiligo/hypermelanosis. It also included databases such as VigiAccess containing data from spontaneous reporting schemes for ADRs. Results: A total of 55 articles (47 clinical trials and 8 case reports) met the inclusion criteria. Some trials did not reported safety information, some did report, but not very well. Reports of blistering, erythema, acute hepatitis and mutagenesis with Psoralea corylifolia. Adverse effects of erythema (mild to severe), phototoxic reactions, mild raise in liver transaminases, gastrointestinal disturbances, burns, itching, scaling, depigmented macules, pruritis, and giddiness with the use of psoralens. Khellin-related erythema, perilesional hyperpigmentation, gastrointestinal disturbances, mild raise in liver transaminases and orthostatic complaints. Infrequent side effects with Ginkgo biloba. Lower grade of erythema and edema reported with the use of Polypodium leucotomos. Conclusion: Primarily the retrieved clinical studies were efficacy oriented and safety parameters were secondary in priority whilst the general protocol of clinical trials requires the screening of drugs/medicinal plants on the basis of safety studies before testing the clinical aspects of efficacy. Thereby it is recommended that efficacy studies may be followed once the safety has been established for a particular medicinal plant in treating vitiligo and hypermelanosis.
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Grape seeds are a by-product of the wine industry. They represent 38­–­­­­­52% of grape pomace and about 5% of the weight of grapes. The main objective of this study is to establish some important characteristics of grape seeds from red varieties cultivated in Romania. The analyzed grape varieties were Cabernet Sauvignon, Merlot, Pinot noir, Burgund Mare, Cadarcă, Syrah, Novac. The grape seeds were dried and ground and the following determinations were made: determination of total polyphenol content, antioxidant capacity, antiradical capacity and determination of phenolic compounds. The analyses were performed on the first day after obtaining the grape extract, on the 14th day and the 30th day. The obtained results demonstrate that all the analyzed samples have a high content of polyphenols and show antioxidant and antiradical capacity. The highest values were obtained on the first day after separation, drying, grinding and extraction of the grape seeds and began to decrease almost constantly in time, so that for 30 days from storage the values obtained could ensure good operating yields. The seeds from the Novac grape variety obtained the best results throughout the analysis period. In the case of the total polyphenol content, the average value of the three samples Novac was 394.57 mgGAE/g dry extract and the average value of antioxidant capacity was 284.35 mgAAE/g dry extract. The greatest antiradical capacity was presented by the seeds of the Syrah and Novac varieties. The average value of the three samples from the Syrah variety was 62.1%, and in the case of the Novac variety was 61.33%. The paper demonstrates the opportunity of superior capitalization of seeds from the seven grape varieties cultivated on the territory of Romania due to the characteristics it possesses. At present, there is a major interest of consumers in the most natural products, with a major contribution to increasing the body's immunity. The use of natural compounds in the food and pharmaceutical industry can be an important alternative.
Article
This review article examines evidence supporting the use of oral therapies in treating idiopathic, actinic, and metabolically induced skin hyperpigmentation. A thorough review of the literature regarding oral treatments for hyperpigmentation was systematically conducted through PubMed. Keywords used in the primary search include “Hyperpigmentation,” “Melanosis” or “Melasma,” “Lightening,” “Oral,” and “Therapeutics.” The search was limited to the English language, and no timeframe restrictions were implemented. Numerous orally administered therapies have been proposed for the treatment of skin hyperpigmentation. There is an abundant body of literature demonstrating the efficacy of orally administered tranexamic acid, glutathione, isotretinoin, and proanthocyanidin. It is reasonable to expect that the most effective oral therapies will address known underlying causes of hyperpigmentation such as thyroid disease, diabetes, and hormonal imbalance. Improvement due to oral therapy of otherwise unresponsive skin hyperpigmentation or hyperpigmentation of unknown cause is less predictable. This review is limited by the strength of evidence contained within the available studies. Clinical studies investigating the treatments discussed within this article are limited in number, at times lack blinding in the study design, and are based on small sample sizes. Based on existing research, the most promising oral remedies for hyperpigmentation appear to be tranexamic acid, glutathione, isotretinoin, and proanthocyanidin. Additional studies to better establish safety and efficacy are necessary.
Article
The potential role of plant-based foods in the promotion of skin health is an emerging area of nutrition research. Plant-based foods are rich in bioactive compounds, including vitamin C, vitamin E, beta-carotene, polyphenols, and phenolic acids, which can contribute to oxidant defense, lower inflammation, and promote structural support of the skin. Epidemiological studies have associated higher intakes of select fruits and vegetables with positive skin health.1,2 Beneficial effects of certain fruits, vegetables, nuts, legumes, and polyphenolic-rich beverages on the skin have been reported, with each of these providing a unique phytochemical composition. While most studies use extracts, this review will focus on data from whole foods and minimally processed products. Collectively, the evidence to date suggests a promising future for plant-based dietary interventions that promote skin barrier health and function. However, additional research is required to address issues such as the optimal quality and duration of intake as well as potential mechanisms. Studies in the above areas will help formulate specific targeted dietary recommendations.
Chapter
This chapter aims to evaluate some of the key considerations when assessing and testing herbal based cosmetic products, including the scientific basis and clinical trials of the most commonly used herbal ingredients. Botanicals contain terpenoids, alkaloids, and phenolics, which have been chemically characterized for their biological effects. Since most skin conditions and diseases are multifactorial with multiple mechanisms of action inducing the visible changes, herbal products would be expected to produce visible benefit. The skin care practitioner should select an herb for a specific desired beneficial effect based on scientific research and/or traditional medical knowledge founded on ethnobotany. Patients and clients entrust skincare professionals to create effective and safe regimens for their skin, yet there are no safety requirements for cosmeceuticals. Coffea arabica yields three commercial products: coffee beans which are the seeds, the fruit which is coffeeberry and coffee charcoal which is roasted fruit until black.
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Melasma is a common malady affecting all races with a higher incidence in Hispanics, Middle Eastern, Asians and African origin females (Fitzpatrick skin phototypes III‐V). Women are affected much more often than men. Melasma remains a significant cause of cosmetic morbidity and psychosocial embarrassment affecting quality of life necessitating effective and reliable treatment. Unfortunately, treatment remains unsatisfactory due to limited efficacy, adverse effects and relapses after stopping treatment. Although chemical peels, laser and light therapies and dermabrasion may have utility, the evidence available for their efficacy is limited and they often cause post inflammatory hyperpigmentation particularly in individuals with darker skin types. Medical therapies remain mainstay in the management of melasma. The triple combination, hydroquinone 4%, tretinoin 0.05% and fluocinolone acetonide 0.01% (Triluma, Galderma, Ft. Worth Texas, often modified incorporating different corticosteroids) remains the only US FDA approved treatment for melasma and is the gold standard due its demonstrated efficacy across ethnicities. Oral tranexamic acid alone or in combination with other modalities has also shown significant efficacy. Several cosmeceuticals and botanical extracts used as skin lightening agents have been demonstrated to be useful. Physical sunscreens containing zinc oxide, iron oxide, titanium dioxide, and silicones provide photoprotective and camouflage effect. We propose that a multimodality approach to the treatment of melasma is the most effective treatment approach. This review is focused on the medical therapies for melasma.
Chapter
IntroductionInternational regulationsFactors affecting concentration and quality of active ingredientsExtraction methodsQuality controlSafetyEffectivenessMechanism of action of herbal actives via secondary metabolitesCosmeceutical product developmentSpecific safety issuesSpecific herbs with esthetic utilityConclusions References
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Melasma (or chloasma) is a common disorder of cutaneous hyperpigmentation predominantly affecting sun-exposed areas in women. The pathogenesis of melasma is not fully understood and treatments are frequently disappointing and often associated with side effects. Pycnogenol® is a standardized extract of the bark of the French maritime pine (Pinus pinaster), a well-known, potent antioxidant. Studies in vitro show that Pycnogenol® is several times more powerful than vitamin E and vitamin C. In addition, it recycles vitamin C, regenerates vitamin E and increases the endogenous antioxidant enzyme system. Pycnogenol® protects against ultraviolet (UV) radiation. Therefore its efficacy in the treatment of melasma was investigated. Thirty women with melasma completed a 30-day clinical trial in which they took one 25 mg tablet of Pycnogenol® with meals three times daily, i.e. 75 mg Pycnogenol® per day. These patients were evaluated clinically by parameters such as the melasma area index, pigmentary intensity index and by routine blood and urine tests. After a 30-day treatment, the average melasma area of the patients decreased by 25.86 ± 20.39 mm2 (p < 0.001) and the average pigmentary intensity decreased by 0.47 ± 0.51 unit (p < 0.001). The general effective rate was 80%. No side effect was observed. The results of the blood and urine test parameters at baseline and at day 30 were within the normal range. Moreover, several other associated symptoms such as fatigue, constipation, pains in the body and anxiety were also improved. To conclude, Pycnogenol® was shown to be therapeutically effective and safe in patients suffering from melasma. Copyright
Article
The International Commission on Illumination (CIE) has recommended the use of two approximately uniform color spaces and associated color-difference formulae chosen from among several of similar merit to promote uniformity of practice. In this paper, the various features of the two formulae are discussed and compared. It is shown that the two are approximately equal in their degree of agreement with visual judgements of color difference. Choice of which formula to use in a particular situation will often depend not so much on scientific merit as on other factors such as familiarity and conformance to common practice in a particular industry or group.
Article
Two types of portable reflectance instruments, tristimulus colorimeters (Chroma Meter CR-200®) and narrow-band spectro-photometers (Dermaspectrometer®), have recently become available for the quantification of skin color. In order to know the difference and the relationship between the different color systems, the CIE L*a*b* system and the erythema melanin (E/M) indices, respectively, adopted by the two, the variations in skin color were measured at 23 different anatomical sites of 10 healthy Caucasian male subjects. The reddish tint of the skin color of the face, palm and sole was readily detected by either of them in the increase in the a* value or in the E index, and a strong linear correlation (r = 0.92, p < 0.001) was noted between the two values. The fair color appearance of the trunk was detected in the high L* value and in the low M index, but the correlation between the two was much less significant (r = -0.56, p < 0.001). Although the mean b* values were highest in the trunk, they are significantly lower on the non-light-exposed side than those on the light-exposed side of the arm. The correlation between the b* value and the M index was weak.
Article
Epicatechin 3-O-gallate and various procyanidins obtained from grape seeds were tested for their scavenger capacity for superoxide radical (O2̇-) and hydroxyl radical (̇OH) in aqueous models. Quantification of O2̇- and ̇OH scavenger capacities was carried out, respectively, by polarography and by the extent of deoxyribose degradation. All the compounds assayed are potent scavengers of these radicals compared to trolox (for D2̇-) and ethanol and mannitol (for ̇OH). Catechin monomers are also potent scavengers, especially of ̇OH. Gallic acid esterification increased the O2̇- and ̇OH scavenger capacity of the dimer procyanidins. However, esterification position was also important. A difference in the O2̇- scavenger capacity was noted between dimers having a C4-C6 and C4-C8 linkage. Procyanidin B2 3′-O-gallate was found to be the most effective compound in trapping oxygen free radicals.
Article
Summary Background Melasma is a common acquired symmetrical hypermelanosis characterized by irregular light to dark brown macules and patches on sun-exposed areas of the skin. Its histopathological characteristics are not fully understood. Objectives To characterize the histopathological features of facial melasma skin in comparison with adjacent normal skin. Methods Biopsies were taken from both melasma lesional skin and adjacent perilesional normal skin in 56 Korean women with melasma. The sections were stained using haematoxylin and eosin, Fontana–Masson, diastase-resistant periodic acid-Schiff, Masson trichrome and Verhoeff–van Gieson stains, and immunostaining for melanocytes. Data on the changes in number of melanocytes and melanin contents of the epidermis were analysed by a computer-assisted image analysis program. The ultrastructure of the skin was also examined. Results The amount of melanin was significantly increased in all epidermal layers in melasma skin. The staining intensity and number of epidermal melanocytes increased in melasma lesions. Lesional skin showed more prominent solar elastosis compared with normal skin. Melanosomes increased in number and were more widely dispersed in the keratinocytes of the lesional skin. Lesional melanocytes had many more mitochondria, Golgi apparatus, rough endoplasmic reticulum and ribosomes in their cytoplasm. A dihydroxyphenylalanine reaction was apparent in the cisternae and vesicles of the trans-Golgi network in melanocytes from lesional skin. Conclusions Melasma is characterized by epidermal hyperpigmentation, possibly caused both by an increased number of melanocytes and by an increased activity of melanogenic enzymes overlying dermal changes caused by solar radiation.
Article
The flavanol composition of the seeds of 17 varieties of grape cultivated in the main wine-producing areas of Castilla-Leon (Spain) was studied. Twenty-seven different flavan-3-ols of procyanidin type were found, but no prodelphinidins were detected. Minor amounts of four hydrolyzable tannins were also present in the seed extracts of most of the grapes analyzed. All the varieties contained galloyled flavanols, such that their presence could be considered characteristic of the grape seed composition. Some proposals concerning the biosynthesis of flavan-3-ol in the grape seed are also advanced taking into account the compounds found.
Article
Skin colour was evaluated in summer in 91 Caucasian volunteers by means of a Minolta Chroma Meter CR-200, a colour analyser for measuring the reflective colour of surfaces by the tristimulus system. All the subjects were classified for skin type according to Fitzpatrick and minimal erythema dose determined. The skin colour of the buttock was taken to be the constitutive skin colour, and that of the cheek the facultative skin colour. It was found that the chromaticity of exposed skin was noticeably different from that of unexposed skin, being situated to the right of the latter in the chromaticity diagram. This means that skin that is usually exposed to the sun has a more intense red component, presumably because of increased vascularization. Exposed skin also showed lower reflectance (Y) or lightness (L*) than unexposed skin, probably because of pigmentation. Hence delta Y and delta L* give an approximate idea of the tanning capacity of each subject. delta Y and delta L* of skin types II and III were greater than delta Y and delta L* of skin type IV. This means that, with chronic exposure to sunlight, even fair skin can achieve a reasonable pigmentation. It is concluded that constitutive skin colour is a more meaningful parameter than facultative skin colour in assessing skin type.
Article
In humans the major stimulus for cutaneous pigmentation is ultraviolet radiation (UVR). Little is known about the mechanism underlying this response, in part because of the complexity of interactions in whole epidermis. Using a recently developed culture system, human melanocytes were exposed daily to a physiologic range of UVR doses from a solar simulator. Responses were determined 24 hours after the last exposure. There was a dose-related increase in melanin content per cell and uptake of 14C-DOPA, accompanied by growth inhibition. Cells from donors of different racial origin gave proportionately similar increases in melanin, although there were approximately tenfold differences in basal values. Light and electron microscopy revealed UVR-stimulated increases in dendricity as well as melanosome number and degree of melanization, analogous to the well-recognized melanocyte changes following sun exposure of intact skin. Similar responses were seen with Cloudman S91 melanoma cells, although this murine cell line required lower UVR dosages and fewer exposures for maximal stimulation. These data establish that UVR is capable of directly stimulating melanogenesis. Because cyclic AMP elevation has been associated in some settings with increased pigment production by cultured melanocytes, preliminary experiments were conducted to see if the effects of UVR were mediated by cAMP. Both alpha-MSH and isobutylmethylxanthine (IBMX), as positive controls, caused a fourfold increase in cAMP level in human melanocytes and/or S91 cells, but following a dose of UVR sufficient to stimulate pigment production there was no change in cAMP level up to 4 hours after exposure. Thus it appears that the UVR-induced melanogenesis is mediated by cAMP-independent mechanisms.
Article
Identification of growth factors for normal human melanocytes has been significantly aided by the recent development of in vitro culture systems for this cell. Utilizing such a system, we studied the effect of ultraviolet radiation (UVR) on both melanocyte growth and melanization by incorporation of 3H-thymidine and 3H-L-dihydroxyphenyl-alanine (3H-DOPA), respectively. H-thymidine incorporation was found to be significantly stimulated during the first 24 h following a single irradiation. 3H-DOPA incorporation was stimulated after a delay of 2 days postirradiation. Whereas UVR has long been known to induce melanocyte proliferation in vivo, these studies show that UVR can act as a mitogenic stimulus for this cell independent of the cutaneous environment. UVR can thus be added to a growing list of growth factors for epidermal pigment cells and is the only physical agent conclusively shown to act as a mitogen. Included in this list are substances that act via stimulation of the CAMP-kinase or protein kinase systems such as cholera toxin and phorbol esters. UVR is postulated to induce melanocyte proliferation by modulation of these second messenger pathways. With recent evidence linking growth factors, oncogenes and malignant transformation, this study supports the association between UVR exposure and the development of malignant melanoma, and suggests mechanisms whereby UVR may contribute to malignant transformation of this cell.
Article
A portable reflectance instrument for the rapid quantification of cutaneous haemoglobin and melanin is presented. Light emitting diodes (LEDS) are used to illuminate the skin and a silicon photodiode to detect the light diffusely reflected from the surface. Reflectance measurements are made at only three wavelengths and the problems of pigment quantification consequent upon this are discussed. In addition to quantification of haemoglobin and melanin, qualitative information on the redox state of the blood may also be obtained. Measurements made on a port wine stain, which had been treated with 576 nm CW laser radiation at times between 1 and 6 months previously, provided information on the vascular response to this thermal injury. Despite the treated area visually appearing normal at 6 months post-treatment the measured levels of deoxygenated and total haemoglobin were still markedly higher than those in the adjacent uninvolved skin. The cutaneous pigment indices are insensitive to skin movement and almost all body sites are suitable for measurement.
Article
A multi-clinical double-blind study on therapeutic effect of combination preparation of vitamins E and C was undertaken in comparison with single preparation of vitamin E and vitamin C in the treatment of chloasma or pigmented contact dermatitis (PCD). Combination treatment resulted in significantly better clinical improvement than vitamin C alone in both diseases. Objective data compiled from color difference measurements and color photographs revealed significantly better results with combination treatment in chloasma than vitamin C alone and, in PCD, than vitamin E or C alone. Differences in skin luminosity between hyperpigmented and normal areas significantly decreased in all three groups, with the combination group producing the most significant change. The total serum lipoperoxide level and its ratio to total serum lipids tended to decline in the combination group, and decreased significantly in vitamin E group. The sebum lipoperoxide level decreased significantly only in the combination group (EC).
Article
A theoretical treatment has been developed for the optical properties of a layered structure which absorbs and scatters light. This theory predicts that the logarithm of the inverse of reflectance (LIR) of the surface should be a useful parameter for the examination of that structure. This approach has been applied to a study of skin in vivo. An instrument was constructed for use in clinical situations to measure the LIR spectrum of skin over the visible region of the spectrum (450-760 nm). The contributions to the observed spectra made by pigments and the skin structure were deduced by reference to the theoretical model. Numerical indices were used to quantify the changes in skin haemoglobin content following the application of vasoconstricting preparations. The indices also provided a means of measuring erythema and melanin pigmentation induced in the skin by exposure to ultraviolet radiation. The assessments made using this instrument were more reproducible and sensitive than judgments made by eye.
Article
Two types of portable reflectance instruments, tristimulus colorimeters (Chroma Meter CR-200) and narrow-band spectrophotometers (Dermaspectrometer), have recently become available for the quantification of skin color. In order to know the difference and the relationship between the different color systems, the CIE L*a*b* system and the erythema melanin (E/M) indices, respectively, adopted by the two, the variations in skin color were measured at 23 different anatomical sites of 10 healthy Caucasian male subjects. The reddish tint of the skin color of the face, palm and sole was readily detected by either of them in the increase in the a* value or in the E index, and a strong linear correlation (r = 0.92, p < 0.001) was noted between the two values. The fair color appearance of the trunk was detected in the high L* value and in the low M index, but the correlation between the two was much less significant (r = -0.56, p < 0.001). Although the mean b* values were highest in the trunk, they are significantly lower on the non-light-exposed side than those on the light-exposed side of the arm. The correlation between the b* value and the M index was weak.
Article
Interleukin (IL)-8 is a member of the supergene family of proinflammatory and chemotactic cytokines recently termed chemokines. IL-8 has been implicated in the pathogenesis of inflammatory skin diseases such as psoriasis. In this study, IL-8 mRNA expression and protein production were determined in normal cultured human epidermal keratinocytes after ultraviolet-B (UVB) irradiation. Messenger RNA levels were determined by the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Total RNA was extracted from cultured keratinocytes at various time points post-irradiation, reverse transcribed to cDNA, and amplified by PCR using a labeled specific primer for the target gene. Amplified products were sized by electrophoresis, visualized by autoradiography, and quantitated by densitometry. Autoradiographs were normalized relative to glyceraldehyde-3-phosphate-dehydrogenase (G3PDH) signals. Constitutive expression of IL-8 mRNA was seen in normal cultured keratinocytes. After 100 or 300 J/m2 UVB irradiation, a rapid increase in IL-8 mRNA level was observed within 1 h after irradiation. At 24 h after irradiation, the mRNA level was elevated 11-13 times compared with the control level. Production of IL-8 protein in culture supernatants was assayed by enzyme-linked immunosorbent assay (ELISA). Significant levels of IL-8 protein were observed at 24 h after irradiation. Cycloheximide treatment blocked this IL-8 protein induction. As IL-8 is known to be an inflammatory cell chemotactic factor, these results suggest a possible role for IL-8 in UVB-induced skin inflammation and diseases.
Article
The skin is an active, and in many ways unique, immunological microenvironment quite different from the other primary interfaces between the body and the environment (namely the mucosae). Here Jan D. Bos and Martien L. Kapsenberg identify the components of the skin immune system and describe the inflammatory and immunological responses that they can mount. New findings with regard to the immunophysiology and physiopathology of the human integument are emphasized.
Article
An inhibitory effect of ascorbic acid (AsA) on melanogenesis has been described. However, AsA is quickly oxidized and decomposed in aqueous solution and thus is not generally useful as a depigmenting agent. Our purpose was to examine the effect on pigmentation of magnesium-L-ascorbyl-2-phosphate (VC-PMG), a stable derivative of AsA. Percutaneous absorption of VC-PMG was examined in dermatomed human skin, and its effect on melanin production by mammalian tyrosinase and human melanoma cells in culture was also measured. A 10% VC-PMG cream was applied to the patients. VC-PMG suppressed melanin formation by tyrosinase and melanoma cells. In situ experiments demonstrated that VC-PMG cream was absorbed into the epidermis and that 1.6% remained 48 hours after application. The lightening effect was significant in 19 of 34 patients with chloasma or senile freckles and in 3 of 25 patients with normal skin. VC-PMG is effective in reducing skin hyperpigmentation in some patients.
Article
Work in the past 8 years, particularly in the past 1-2 years, has greatly expanded our understanding of the mechanisms by which ultraviolet irradiation stimulates melanogenesis in the skin. A direct effect of UV photons on DNA results in up-regulation of the gene for tyrosinase, the rate-limiting enzyme in melanin synthesis, as well as an increase in cell surface expression of receptors for at least one of the several known keratinocyte-derived melanogenic factors, MSH. Direct effects of UV on melanocyte membranes, releasing DAG and arachidonic acid, may also play a role in the tanning response. Diacylglycerol may activate PKC-beta, which in turn phosphorylates and activates tyrosinase protein; the pathways by which products of other inflammatory mediator cascades may act on melanogenesis are unknown. The tanning response also relies heavily on UV-stimulated increased production and release of numerous keratinocyte-derived factors including bFGF, NGF, endothelin-1 and the POMC-derived peptides MSH, ACTH, beta-LPH and beta-endorphin. These factors variably induce melanocyte mitosis, increase melanogenesis, enhance dendricity and prevent apoptotic cell death following the UV injury. Thus, events within the epidermal melanin unit conspire to maintain or increase melanocyte number, increase melanin pigment throughout the epidermis. Overall, ultraviolet-induced melanogenesis may be one part of a eukaryotic SOS response to damaging ultraviolet irradiation that has evolved over time to provide a protective tan in skin at risk of further injury from sun exposure. These recent insights into the mechanisms underlying ultraviolet-induced melanogenesis offer the opportunity for novel therapeutic approaches to minimizing acute and chronic photodamage in human skin.
Article
Although the ability of UV irradiation to induce pigmentation in vivo and in vitro is well documented, the intracellular signals that trigger this response are poorly understood. We have recently shown that increasing DNA repair after irradiation enhances UV-induced melanization. Moreover, addition of small DNA fragments, particularly thymine dinucleotides (pTpT), selected to mimic sequences excised during the repair of UV-induced DNA photoproducts, to unirradiated pigment cells in vitro or to guinea pig skin in vivo induces a pigment response indistinguishable from UV-induced tanning. Here we present further evidence that DNA damage and/or the repair of this damage increases melanization. (i) Treatment with the restriction enzyme Pvu II or the DNA-damaging chemical agents methyl methanesulfonate (MMS) or 4-nitroquinoline 1-oxide (4-NQO) produces a 4- to 10-fold increase in melanin content in Cloudman S91 murine melanoma cells and an up to 70% increase in normal human melanocytes, (ii) UV irradiation, MMS, and pTpT all upregulate the mRNA level for tyrosinase, the rate-limiting enzyme in melanin biosynthesis. (iii) Treatment with pTpT or MMS increases the response of S91 cells to melanocyte-stimulating hormone (MSH) and increases the binding of MSH to its cell surface receptor, as has been reported for UV irradiation. Together, these data suggest that UV-induced DNA damage and/or the repair of this damage is an important signal in the pigmentation response to UV irradiation. Because Pvu II acts exclusively on DNA and because MMS and 4-NQO, at the concentrations used, primarily interact with DNA, such a stimulus alone appears sufficient to induce melanogenesis. Of possible practical importance, the dinucleotide pTpT mimics most, if not all, of the effects of UV irradiation on pigmentation, tyrosinase mRNA regulation, and response to MSH without the requirement for antecedent DNA damage.
1. The comparative protective abilities of a grape seed proanthocyanidin extract (GSPE) (25-100 mg/kg), vitamin C (100 mg/kg), vitamin E succinate (VES) (100 mg/kg) and beta-carotene (50 mg/kg) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lipid peroxidation and DNA fragmentation in the hepatic and brain tissues, as well as production of reactive oxygen species by peritoneal macrophages, were assessed. 2. Treatment of mice with GSPE (100 mg/kg), vitamin C, VES and beta-carotene decreased TPA-induced production of reactive oxygen species, as evidenced by decreases in the chemiluminescence response in peritoneal macrophages by approximately 70%, 18%, 47% and 16%, respectively, and cytochrome c reduction by approximately 65%, 15%, 37% and 19%, respectively, compared with controls. 3. GSPE, vitamin C, VES and beta-carotene decreased TPA-induced DNA fragmentation by approximately 47%, 10%, 30% and 11%, respectively, in the hepatic tissues, and 50%, 14%, 31% and 11%, respectively, in the brain tissues, at the doses that were used. Similar results were observed with respect to lipid peroxidation in hepatic mitochondria and microsomes and in brain homogenates. 4. GSPE exhibited a dose-dependent inhibition of TPA-induced lipid peroxidation and DNA fragmentation in liver and brain, as well as a dose-dependent inhibition of TPA-induced reactive oxygen species production in peritoneal macrophages. 5. GSPE and other antioxidants provided significant protection against TPA-induced oxidative damage, with GSPE providing better protection than did other antioxidants at the doses that were employed.
Article
Analysis of the expression of a number of known genes in cultured human cells has revealed UVB-induced changes that may be specific for melanocytic cells. The response of c-fos, p53 and HIV-LTR reporter constructs to UVB and UVC was reduced in MM96L melanoma cells compared to HeLa. Cell cycle arrest produced by UVA, gamma radiation, cisplatin or the antimetabolite deoxyinosine differed from that of UVB. Cell cycle analysis after multiple doses of UVB raised the possibility that UVB-induced pRb depletion could result in increased mutation and thus enhanced tumourigenesis of irradiated melanocytes in skin subjected to a defined pattern of UVB exposure. To extend the analysis of gene expression in cultured melanocytic cells to uncharacterised genes, promoter trap cell clones containing unknown genes 'tagged' by a beta-galactosidase reporter construct were generated from MM96L cells. Altered gene expression in clones treated with a panel of DNA-damaging agents was quantitated by measurement of beta-galactosidase activity. Of the clones containing 'tagged' endogenous promoters induced by UVB, 52% were induced only by UVB and not by other DNA-damaging agents (cisplatin, N-methyl-N-nitro-nitrsoguanidine, fotemustine). One third of the clones were also activated by TPA suggesting that general DNA damage responses involving PKC are activated less frequently than unique pathways of gene activation. Overall, 60% of the 50 clones that responded to the panel of agents were induced by only one of the agents, indicating that a high proportion of genes are induced by agent-specific mechanisms. In the long term, promoter trapping may allow the full repertoire of UVB-inducible genes to be characterised.
Article
The effect of a single oral administration of proanthocyanidins, oligomeric and polymeric polyhydroxyflavan-3-ol units, on the antioxidative potential of blood plasma was studied in rats. Proanthocyanidin-rich extract from grape seeds was administered by intragastric intubation to fasted rats at 250 mg/kg of body weight. The plasma obtained from water- or proanthocyanidin-administered rats was oxidized by incubation with copper sulfate or 2, 2'-azobis(2-amidinopropane) dihydrochloride (AAPH) at 37 degrees C, and the formation of cholesteryl ester hydroperoxides (CE-OOH) was followed. The plasma obtained from proanthocyanidin-administered rats was significantly more resistant against both copper ion-induced and AAPH-induced formation of CE-OOH than that from control rats. The lag phase in the copper ion-induced oxidation of rat plasma was remarkably increased at 15 min after administration of proanthocyanidins and reached a maximum level at 30 min. When the plasma from proanthocyanidin-administered rat was hydrolyzed by sulfatase and beta-glucuronidase following analysis by high-performance liquid chromatography with electrochemical detection, metabolites of proanthocyanidins occurred in rat plasma at 15 min after administration, three peaks of which were identified as gallic acid, (+)-catechin, and (-)-epicatechin. These results suggest that the intake of proanthocyanidins, the major polyphenols in red wine, increases the resistance of blood plasma against oxidative stress and may contribute to physiological functions of plant food including wine through their in vivo antioxidative ability.
Article
The scavenging effects of grape seed extract (GSE) on free radicals formed in an H(2)O(2)/NaOH/DMSO system were examined using a spin-trapping electron spin resonance (ESR) method and compared with other natural antioxidants, ascorbic acid, dl-alpha-tocopherol, and beta-carotene. GSE reduced greatly the ESR signal intensity of superoxide radical-5,5-dimethyl-1-pyrroline-N-oxide (DMPO) adducts. GSE also exhibited weak scavenging activity on hydroxyl radical and a little scavenging activity on methyl radical. Ascorbic acid exhibited strong superoxide and hydroxyl radical scavenging activities, but it increased the amount of methyl radical at high concentration. dl-alpha-Tocopherol reduced the amount of superoxide anion, especially the amount of methyl radical. However, it slightly reduced the amount of hydroxyl radical. beta-Carotene reduced the amount of hydroxyl radical and methyl radical, but it also slightly reduced superoxide anion. In the case of combination use of beta-carotene and dl-alpha-tocopherol, all radical species were suppressed. Combination of GSE and dl-alpha-tocopherol also could reduce all radical species. beta-Carotene and dl-alpha-tocopherol could reduce the methyl radical formation induced by ascorbic acid.
Article
A great many epidemiological studies indicate that a diet rich in flavonoids can reduce the incidence of coronary artery disease. Regular moderate consumption of wine can contribute to this phenomenon. Flavonoids in wine and food have been shown to be antioxidant and anti-aggregant in vitro and could indeed help protect against coronary disease. However, the epidemiological studies in this field are based on data concerning the flavonoid composition of foods, and the contribution of a regular, moderate consumption of wine remains difficult to quantify. In this study, we have tried to obtain a first estimation of catechin and procyanidin contents. We also discuss the metabolism of these molecules and the appearance of (+)-catechin in the plasma.
Article
Ultraviolet (UV) B irradiation evokes erythema and delayed pigmentation in skin, where a variety of toxic and modulating events are known to be involved. Nitric oxide (NO) is generated from L-arginine by NO synthases (NOS). Production of NO is enhanced in response to UVB-stimulation and has an important role in the development of erythema. NO has recently been demonstrated as a melanogen which stimulates melanocytes in vitro, however, no known in vivo data has been reported to support this finding. In this study, we investigated the contribution of NO with UV-induced pigmentation in an animal model using an NOS inhibitor. UVB-induced erythema in guinea pig skin was reduced when an NOS inhibitor, L-NAME (N-nitro-L-arginine methylester hydrochloride), was topically applied to the skin daily, beginning 3 days before UVB-irradiation. Delayed pigmentation and an increased number of DOPA-positive melanocytes in the skin were markedly suppressed by sequential daily treatment with L-NAME. Furthermore, melanin content 13 days after UVB-irradiation was significantly lower in skin treated with L-NAME than in the controls. In contrast, D-NAME (N-nitro-D-arginine methylester hydrochloride), an ineffective isomer of L-NAME, demonstrated no effect on these UV-induced skin responses. These results suggest that NO production may contribute to the regulation of UVB-induced pigmentation.
Article
Facial and neck pigmentations are the most cosmetically important. They are common in middle-aged women, and are related to endogenous (hormones) and exogenous factors (such as use of cosmetics and perfumes, and exposure to sun radiation). Melasma (chloasma) is the most common cause of facial pigmentation, but there are many other forms such as Riehl’s melanosis, poikiloderma of Civatte, erythrose peribuccale pigmentaire of Brocq, erythromelanosis follicularis of the face and neck, linea fusca, and cosmetic hyperpigmentations. Treatment of melasma and other facial pigmentations has always been challenging and discouraging. It is important to avoid exposure to the sun or to ultraviolet lamps, and to use broad-spectrum sunscreens. Several hypopigmenting agents have been used with differing results. Topical hydroquinone 2 to 4% alone or in combination with tretinoin 0.05 to 0.1 % is an established treatment. Topical azelaic acid 15 to 20% can be as efficacious as hydroquinone, but is less of an irritant. Tretinoin is especially useful in treating hyperpigmentation of photoaged skin. Kojic acid, alone or in combination with glycolic acid or hydroquinone, has shown good results, due to its inhibitory action on tyrosinase. Chemical peels are useful to treat melasma: trichloroacetic acid, Jessner’s solution, Unna’s paste, α-hydroxy acid preparations, kojic acid, and salicylic acid, alone or in various combinations have shown good results. In contrast, laser therapies have not produced completely satisfactory results, because they can induce hyperpigmentation and recurrences can occur. New laser approaches could be successful at clearing facial hyperpigmentation in the future.
Article
Antioxidants such as vitamins C and E have been reported to inhibit the progression of ultraviolet (UV) radiation-induced pigmentation in the skin of hairless mice. However, little is known of the lightening effect of proanthocyanidin, a powerful polyphenolic antioxidant, on UV-induced pigmentation of the skin. We investigated the lightening effect of oral administration of a proanthocyanidin-rich grape seed extract (GSE) using guinea pigs with UV-induced pigmentation. These pigmented guinea pigs were fed diets containing 1% GSE or 1% vitamin C (w/w) for 8 weeks. GSE-feeding had an apparent lightening effect on the guinea pigs' pigmented skin. Histologic evaluation demonstrated a decrease in the number of 3,4-dihydroxyphenylalanine (DOPA)-positive melanocytes as well as 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive, Ki-67-positive, proliferating cell nuclear antigen (PCNA)-positive melanin-containing cells in the basal epidermal layer of the UV-irradiated skin in GSE-fed guinea pigs. In contrast, these parameters did not change in the skin of vitamin C-fed or control guinea pigs. GSE inhibited the activity of mushroom tyrosinase and also inhibited melanogenesis without inhibiting the growth of cultured B16 mouse melanoma cells. In conclusion, we demonstrated that oral administration of GSE is effective in lightening the UV-induced pigmentation of guinea pig skin. This effect may be related to the inhibition of melanin synthesis by tyrosinase in melanocytes and the reactive oxygen species (ROS)-related proliferation of melanocytes.
Nutrition of grape phenolics
  • Al Waterhouse
  • Rl Walzem
Waterhouse AL, Walzem RL. 1998. Nutrition of grape phenolics. In Flavonoids in Health and Disease, Rice-Evans CA, Packer L (eds). Marcel Dekkar: New York; 359–385.