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Oral intake of proanthocyanidin-rich extract from grape seeds improves chloasma
Phytotherapy Research
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.
... 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. ...
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.
... Interestingly, the blend of botanical extracts that made up Belight 3TM showed a synergistic effect on the tyrosinase inhibition that was greater than extracts tested alone. This synergy may be driven by specific flavonoids such as flavanol monomers from grape seed and glabridin from licorice as previously suggested [22][23][24]. ...
... A licorice extract and in particular glycyrrhizic acid have been allowed for use in foods by the United States Food and Drug Administration, the Council of Europe and the Joint FAO/WHO Expert Committee on Food Additives and have been recognized as generally safe [30]. Although hair graying has never been associated with the administration of skin lightening food supplements including polyphenols or vitamin C [14,24,31], one limitation of the study design is the absence of hair graying or whitening assessment before and after product intake. As this oral formulation may lead to systemic inhibition of tyrosinase activity, we can hypothesize that melanogenesis may also be inhibited in the hair, leading to hair whitening. ...
Oral formulations with natural plant-based extracts represent a safe and promising strategy for skin lightening and anti-dark-spot effects, especially in Asia. This study evaluated the effect of an oral formulation including polyphenol-rich extracts and vitamin C (Belight3TM) on in vitro tyrosinase inhibitory activity and investigated its skin lightening and anti-dark-spot effects in vivo. Tyrosinase inhibitory activity of the formulation was measured with spectrophotometry. A randomized, double-blind, placebo-controlled clinical study was carried out on 58 healthy Asian males and females, aged 45–65. Skin color was measured at baseline, 6 weeks and 12 weeks with digital photographs. Color of dark spots was assessed with spectrophotometry. In vitro, the formulation showed a significant synergistic tyrosinase inhibitory activity of 85% compared to the control. In vivo, 12-week oral administration of the formulation significantly lightened the skin and was significantly better than the placebo. In addition, this formulation induced a slight and significant lightening effect of the dark spots after 6 and 12 weeks. Our findings suggest that the daily oral administration of Belight3TM during 12 weeks appears as an efficient and safe nutricosmetic to lighten the color of the facial skin and dark spots in Asian subjects.
... 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. ...
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
... 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. ...
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.
... 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. ...
... Therefore, building on the previous clinical study conducted on an Asian population [43], the administration of Belight 3TM confirmed its overall lightening effect on dark spots and strengthened the indication that an oral administration of selected mixtures of ingredients, such as this combination of polyphenol-rich extracts from grape seed, grape pomace, and licorice root extract, can achieve systemic inhibition of tyrosinase without any side effects. Although the potential biological mechanisms of dark spot lightening need to be deeply elucidated, this synergy may be driven by specific flavonoids such as flavanol monomers, stilbenes like viniferins, and glabridin that possess known antioxidant, anti-inflammatory, or tyrosinase inhibition activities [47][48][49]. ...
Belight3TM, a nutricosmetic formulation containing polyphenol-rich extracts, has previously been demonstrated to be safe and effective in brightening skin color and dark spots in a clinical study involving Asian volunteers. The aim of this study was to investigate the efficacy of this formulation in lightening dark spots in a Caucasian population, which is characterized by lighter skin pigmentation and greater visibility of hyperpigmentation, as well as to determine whether the supplementation increased sensitivity to UV exposure. A randomized, double-blind, placebo-controlled clinical study was conducted on 66 male and female participants with skin phototype I to III, all exhibiting facial hyperpigmentation. The color of selected dark spots was assessed using spectrophotometry to measure the L* value of the CIELab color space and the Individual Typology Angle (ITA). L* and ITA levels of dark spots were significantly increased after 6 and 12 weeks of Belight3TM treatment (respectively by +1.2% and +2.5% for L* and by 12.1% and 22.5% for ITA), and this lightening effect was significantly higher than the placebo after 12 weeks (p < 0.05 for L*; p < 0.001 for ITA). Clinical evaluation of skin complexion evenness and dark spot visibility were also improved in subjects receiving the Belight3TM treatment, achieving a significant difference with the placebo after 12 weeks. No changes in MED or skin redness were observed during this study. This study confirmed the safety and efficacy of Belight3TM in lightening dark spots in a Caucasian population without increasing UV sensitivity.
... Anthocyanins have previously been reported as potentially effective compounds to protect the skin from oxidative stress and inflammation, although further clinical validation is still needed [61]. Additionally, proanthocyanidin-rich food extracts have already demonstrated beneficial effects on skin pigmentation [62][63][64][65]. For example, a French maritime pine bark extract was demonstrated to reduce skin photoaging and the pigmentation of age spots in women with mild to moderate photoaging [63], while apple proanthocyanidins have been shown to alleviate the skin pigmentation induced by UV in healthy women [65]. ...
Strategies for successful aging, including the use of food supplements, are part of the approach to support skin youthfulness. To demonstrate the efficacy of fermented bilberry extract (FBE) against skin aging and uneven complexion, a clinical trial was carried out on 66 subjects with visible “crow’s feet” wrinkles, mild-to-moderate skin slackness, and uneven skin tone. The wrinkle depth, skin smoothness (Ra) and roughness (Rz), skin firmness (R0) and elasticity (R2), skin coloration (ITA°), and skin antioxidant capacity were measured before and after 28 (D28), 56 (D56), and 84 (D84) days of product use (either FBE or a placebo). These parameters were also integrated with a clinical evaluation, carried out by a dermatologist, and a self-assessment questionnaire to align the measured efficacy with the visual or perceived efficacy. At D84, the wrinkle depth had decreased by 10.6%, Ra had improved by 7.9%, Rz had decreased by 7.3%, R0 had improved by 13.3%, R2 had improved by 12.4%, and skin antioxidant capacity had increased by 20.8%. ITA° increased by 20.8% and was accompanied by a decrease in the skin’s redness component by 16.8% and an increase in the lightness component by 2.2%. The variation of all the above-mentioned parameters was statistically significant between the FBE and PL groups. Our findings demonstrate the efficacy of FBE in improving skin aging and complexion evenness.
... Due to the lack of side-effects, various plant extracts are being used in various cosmeceuticals creams. Oral intake of grape seed extract for six months has been found beneficial in patients with melasma(Yamakoshi, et al., 2004).Involving the orchid extract, Tadokoro, et al., 2010 has concluded that orchid extract has efficacy similar to vitamin C in reducing melasma and lentigines. However there is paucity of literature regarding their efficacy and side effect profile. ...
Hyperpigmentation is a clinical condition that is occurred due to overproduction of melanin. Melanin is a pigment responsible for occurring pigmentation of the hair, skin and protection of the eyes and skin from sunlight. A variety of synthetic topical agents are available to treat hyperpigmentation. Since, undesirable side effects are associated with synthetic products, natural plant extracts, are considered to develop new products to address hyperpigmentation due to their ready availability, easy affordability to a least possible cost. This study was focused on determining the free radicals scavenging activity and tyrosinase enzyme inhibiting activity of the Glycyrrhiza glabra root extract, Mimosa pudica leaf and pods extracts and to formulate a topical cream. Based on results, all three plant extracts were presented with excellent antioxidant activity indicating IC50 values of 34.26 μg/mL for M. pudica leaf extract 75.09 μg/mL for M. pudica pods extract, 95.82 μg/mL for G. glabra root extract respectively. Mixture of three plant extracts which incorporated into the cream formulation indicated excellent mushroom tyrosinase inhibiting activity resulting IC50 value of 47.47 ± 0.42 μg/mL. The LC50 values of G. glabra root extract, M. pudica leaf and pods extracts were found to be 383.8 μg/mL, 192.1 μg/mL, and 383.8 μg/mL respectively. Initially, cold and vanishing cream bases were developed, and base stability was observed throughout the short term (14 days) and long term (90 days) stability evaluation periods. Then, one vanishing cream base was selected due to its better stability and plant extracts were incorporated and kept to evaluate the accelerated stability (28 days) and long term stability (90 days). Formulated medicated vanishing cream was then subjected to evaluate pH, viscosity, spreadability, microscopic analysis and irritancy to characterize the product. The medicated vanishing cream was in Oil-in-Water type with pH value of 6.5 which is within the non-skin irritant pH range of pH 4-7 and viscosity of 54700 cps with spreadability value of 6.1gcms-1 and was stable throughout the accelerated and long term stability evaluation periods.
... Against electromagnetic radiation hitting human skin, melanin acts as an optical filter to reduce radiation and a chemical filter with a stable free radical function to absorb compounds produced by photochemical action that may be toxic or carcinogenic (Kollias et al. 1991). Biosynthesis of melanin plays a crucial role in protecting the skin by protecting it from sunlight damage (UV radiation absorption), ion accumulation, as well as sequestration of reactive oxygen species (ROS) (Betteridge 2000;Trouba et al. 2002;Yamakoshi et al. 2004;Kaur et al. 2006). ...
This study investigated the effect of some herbal extracts, such as licorice root, white mulberry leaf, green tea leaf, and grape seed, with a combination of bacterial nanocellulose and some bioactive materials, such as ascorbic acid, niacinamide, hexylresorcinol, and alpha-arbutin, on treatment of hyperpigmentation. The effect of the prepared emulsions on hyperpigmentation was revealed by analyzing their tyrosinase inhibition properties, their ability to stop melanin production, or their properties of whitening the brown spot on the skin. In addition to the physicochemical properties of the 5 different emulsions obtained, tyrosinase, collagenase, and elastase enzyme activities, antioxidant properties, cytotoxicity, and microbiological analyzes were performed by cell-culture modelling. Finally, a dermocosmetic facial serum was designed that is compatible with skin pH, is homogeneously mixed, has good spreading properties, does not cause any microbiological growth, does not inhibit elastase activity while stimulating collagenase activity, reduces melanin production by inhibiting the tyrosinase enzyme, and does not have any toxic effects.
... As a natural antioxidant, flavonoids are mainly used to scavenge free radicals, enhance reducing power, and inhibit lipid peroxidation through electron transfer or as hydrogen donors, and their ability to scavenge free radicals is closely related to their pharmacological activity [56]. Yamakoshi et al. [57] found that flavonoids in grape seed extract can chelate metal ions, scavenge free radicals, and act as inhibitors of lipid peroxidation reactions. Alessia Remigante et al. [28] demonstrated that Açai extract prevented D-Gal-induced OS damage, including ROS production, lipid peroxidation, and total protein sulfhydryl oxidation, and restored the distribution of B3p and CD47 on the plasma membrane. ...
To evaluate the antioxidant activity of flavonoids extracted from Chinese herb mulberry leaves (ML), flavonoids from mulberry leaves (FML) were extracted and purified by using ultrasonic-assisted enzymatic extraction and D101 macroporous resin. Using LC-MS/MS-Liquid Chromatography with tandem mass spectrometry analysis, hesperidin, rutoside, hyperoside, cyanidin-3-o-glucoside, myricitrin, cyanidin, and quercetin were identified, and NMR and UV were consistent with the verification of IR flavonoid characteristics. The antioxidant activity of FML has also been evaluated as well as the protective effect on 2,2 0-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress. The results showed that FML exhibited powerful antioxidant activity. Moreover, FML showed dose-dependent protection against AAPH-induced sheep erythrocytes’ oxidative hemolysis. In the enzymatic antioxidant system, pretreatment with high FML maintained the balance of SOD, CAT, and GSH-Px; in the non-enzymatic antioxidant system, the content of MDA can be effectively reduced after FML treatment. This study provides a research basis for the development of natural products from mulberry leaves.
... Grape seed extract (GSE) contains proanthocyanidin, a powerful antioxidant. Although there are no studies on the topical use of grape seed extract, oral intake for 6 months has been found beneficial in patients with melasma in a study conducted by Yamakoshi, et al. [93] L* value and melanin index were measured. Both indices increased after 6 months of grape seed extract intake confirming the depigmenting action of GSE. ...
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.
... 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). ...
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.
... 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. ...
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
... This overproduction of free radicals, which plays an important role in damaging skin cells and in addition leads to a degradation of collagen and elastin which are responsible for the skin firmness, elasticity and the vessels integrity, and hence for the good skin vascularization [8] . 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 [9] . To avoid such cellular damages, a reduction of the amount of secondary oxidants is the complementary step to lower the oxidative stress. ...
Background: The growing field of psycho-dermatology is all about the mind-skin connection. It addresses the link between our emotional state, the body’s physiological response to our emotional state, and the outcome of this response on our skin, body, health, and well-being. The aim of this clinical trial is to evaluate safety and efficacy of BP-G01 in improving skin health, complexion and skin luster. Material and methods: Total 33 subjects were screened and out them 3 were considered as drop outs and 30 completed subjects were involved in the study. Natural plant based skincare supplement (BP-G01) contains Plant based protein blend like Plant proteins like rice and pea proteins. The glow blend like evening primrose extract, pearl powder, orange, pomegranate, grape seed extract, sea buckthorn extract and tocopherols from plant source. The adaptogenic blend like Ashwagandha, Amla, Tulsi, Mulethi and Turmeric extracts. It was consumed as 90 days’ treatment in dose of 20 gm in the morning after breakfast or post workout with 200 ml of water or milk. Natural plant based skincare supplement (BP-G01) improve improved skin luminosity, brightness, radiance and complexion, skin hydration, skin discoloration, dark circles, dark spots from face and neck and skin evenness indicated by MASI scoring for reducing hyper pigmentation, dark spots/ circles and redness and reduction in mild acne counts. VAS for the improvements in skin complexion and evenness. C.L.B.T. imperfections scale. Result: There was 17.08, 22.79, 32.56 and 37.96% reduction in the MASI score at day 15, 30, 60 and day 90 respectively by reducing hyper pigmentation, dark spots/ circles and redness by MASI scoring. MASI acne score at baseline was 9.10 ± 1.19 which was decreased throughout the period of treatment by reduction in mild acne counts as per modified MASI scoring. Conclusion: BP-G01 is safe and effective in promoting skin health in healthy adults.
... 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. ...
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. ...
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.
... Grape seed extract reduces the melanocytes proliferation thus reducing the melanin pigmentation in MELASMA/CHLOASMA which might be one of the reasons for insignificant color difference between the groups. [21] The research hypothesis is accepted as the application of antioxidants 5% grape seed extract and 10% wheat grass extract did not affect the shade of the bleached enamel. ...
Background and Aim: The bleached enamel surface requires application of antioxidant as there will be continuous release of free oxygen radicals. It would be beneficial if remineralizing agent which is recommended after bleaching also provides an antioxidant therapy. The natural antioxidants are colored. Hence, the aim of the present study was to evaluate the effect of natural antioxidants on the shade of the bleached enamel. Materials and Methods: Thirty single rooted maxillary anterior teeth were selected for the study. For all the samples middle third portion of the labial surface of the teeth was standardized using computerized cellophane stickers. Bleaching was carried out with 22% Carbamide peroxide gel (Philips Zoom Nite White). Based on the type of antioxidant solution application, samples were divided into three groups of ten samples each. Group I control (n=10) Group-II (n=10) 10% wheat grass solution (Sresta natural Bio products, India) Group-III (n=10) 5% grape seed extract (Zenith nutrition, Medizen Labs Pvt.Ltd, India). L, a, b values were recorded with spectrophotometry (Vita Zahnfabrik H. RauterGmbH & Co. KG,Bad Sackingen, Germany) thrice for each sample at the three respective time periods i.e at baseline, after bleaching and after antioxidant application. Results: ΔE values were subjected to statistical analysis using one way ANOVA with p>0.05 and the results were tabulated. It was observed that there was statistical insignificant difference between the groups with a p value of 0.295(p>0.05). Conclusion: The antioxidants 5% grape seed extract and 10% wheat grass extract did not affect the shade of the bleached enamel. Keywords: tooth bleaching, antioxidant, shade, spectrophotometry
... 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]. ...
... After 30 days, overall efficacy rate was 80%, and there was a significant decrease in pigmentary intensity and average melasma area. Yamakoshi et al. 85 studied the efficacy of oral grape seed extract for melasma treatment and found a significant decrease in melanin index. ...
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.
... 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. ...
... 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]. ...
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 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. ...
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.
... 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). ...
... 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]. ...
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.
... 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]. ...
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.
... 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. ...
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.
... 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]. ...
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.
... 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. ...
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%.
This review explores the emerging term “gut-skin axis” (GSA), describing the bidirectional signaling that occurs between the skin and the gastrointestinal tract under both homeostatic and disease conditions. Central to GSA communication are the gut and skin microbiota, the microbial communities that colonize these barrier surfaces. By influencing diverse host pathways, including innate immune, vitamin D receptor, and Aryl hydrocarbon receptor signaling, a balanced microbiota contributes to both tissue homeostasis and host defense. In contrast, microbiota imbalance, or dysbiosis at one site, can lead to local barrier dysfunction, resulting in the activation of signaling pathways that can disrupt tissue homeostasis at the other site, potentially leading to inflammatory skin conditions such as atopic dermatitis and psoriasis, or gut diseases like Inflammatory Bowel Disease. To date, most research on the GSA has examined the impact of the gut microbiota and diet on skin health, but recent studies show that exposing the skin to ultraviolet B-light can beneficially modulate both the gut microbiome and intestinal health. Thus, despite the traditional focus of clinicians and researchers on these organ systems as distinct, the GSA offers new opportunities to better understand the pathogenesis of cutaneous and gastrointestinal diseases and promote health at both sites.
It is well-established that both communicable and non-communicable diseases present significant challenges to global healthcare. A substantial proportion, approximately 85%, of these diseases can be attributed to environmental factors. Consequently, adopting a healthy lifestyle can serve as a preventative measure for the majority of these ailments. Research conducted over the past few decades has provided valuable insights into the biological properties of various natural sources, including fruits, vegetables, spices, and millets, as well as their bioactive constituents, with the aim of improving human health. Numerous bioactive compounds, commonly referred to as nutraceuticals, have been isolated from these natural sources. Compounds such as curcumin, piperine, resveratrol, isothiocyanates, epigallocatechin gallate (EGCG), quercetin, sulphoraphane, among others, have demonstrated significant disease-preventive and therapeutic properties against a wide spectrum of human ailments. These assertions are supported by extensive preclinical and clinical studies. Consequently, these nutraceutical agents hold immense potential for the prevention and treatment of diseases. Therefore, the present chapter aims to explain the significance of select nutraceuticals and their applications in promoting human well-being.
Melasma, a prevalent pigmentary disorder, is characterized by its complex etiology, propensity for recurrence, and resistance to treatment. However, there is currently no research on melasma through bibliometrics and visualisation. This study analyses the hotspots and trends in the field based on 2,709 publications from the Web of Science Core Collection (WOSCC). We carried out bibliometric analyses using Citespace software for different countries/regions, institutions, authors, and keywords. References were also analysed using VoSviewer. The results indicate that overall, there has been an increase in publications related to melasma since 2014. According to the analysis of the collaborative network diagram, the United States, Egyptian Knowledge Bank, and Benjakul Soottawat are the most contributing countries, institutions, and authors, respectively. Reference and keyword analyses have identified the pathogenesis and treatment of melasma as a prevalent topic in recent years. And how to find new treatment options and more effective therapeutic drugs is a future research trend. This is the first bibliometric and visual analysis of melasma-related literature to explore research hotspots and trends.
Melasma is a prevalent hyperpigmentation condition known for its challenging treatment due to its resemblance to photoaged skin disorders. Numerous studies have shed light on the intricate nature of melasma, which often bears similarity to photoaging disorders. Various therapeutic approaches, encompassing topical and systemic treatments, chemical peeling, and laser therapy, have exhibited efficacy in managing melasma in previous research. However, melasma often reoccurs despite successful treatment, primarily due to its inherent photoaged properties. Given that melasma shares features with photoaging disorders, including disruptions in the basement membrane, solar elastosis, angiogenesis, and mast cell infiltration in the dermal layer, a comprehensive treatment strategy is imperative. Such an approach might involve addressing epidermal hyperpigmentation while concurrently restoring dermal components. In this article, we provide a comprehensive review of conventional treatment methods frequently employed in clinical practice, as well as innovative treatments currently under development for melasma management. Additionally, we offer an extensive overview of the pathogenesis of melasma.
Cosmeceuticals are hybrids between cosmetics and pharmaceuticals containing ingredients that modify the skin’s functions and enhance its appearance. They are a bridge between drugs and cosmetics for minor skin ailments. The lack of proper regulatory standards for cosmeceuticals makes it very important for the dermatologists to educate the patient regarding their safety, or consequences of lack of knowledge thereof. In hyperpigmentation disorders, cosmeceuticals specifically target melanocytes and block the important regulatory steps in melanin synthesis, especially tyrosinase. The various agents include arbutin, bakuchiol, ferulic acid, kojic acid, licorice root extract, nicotinamide, plant extracts, resorcinol, retinol, sunscreens, thiamidol, and vitamin C. Plant extracts have minimal side-effects and are gaining popularity. They include aloe vera extract, cinnamic acid, coffeeberry, flavonoids, grape seed extract, green tea extracts, marine algae extract, mulberry extract, N-acetyl glucosamine, orchid extract, pycnogel, soy and umbelliferone. There is a requirement for large randomised controlled trials to establish their efficacy and adverse effects. Patient follow-up and compliance are the cornerstones of any skin therapy as any cosmeceutical use can produce gradual results when compared to conventional therapies. The PubMed database was searched using ‘hyperpigmentation disorders’ OR ‘melasma’ AND ‘cosmeceuticals’ as keywords. Abstracts were screened to include studies in the English language and those pertaining to the use of cosmeceuticals in hyperpigmentary disorders. In this review, we summarise the existing literature on the utility of cosmeceuticals in the treatment of hyperpigmentary diseases.
Melasma is a form of inherited hyper-melanosis that appears as asymmetrical, brown-colored, uneven, reticulated macules on UVR-exposed skin, particularly on the facial area. The etiopathogenesis of melasma has been linked to several causes, including UV exposure, endocrine factors, genetic predisposition, anti-epileptic medications, and various cosmetics. The initial course of treatment for hyperpigmentation involves applying topical formulations of widely used substances like kojic acid, glycolic acid, and hydroquinone. Pharmaceuticals such as melatonin, tranexamic acid, and cysteamine hydrochloride are administered orally in this process. Chemical peels and laser therapy are examples of second-line therapies that are applied under the direction of trained experts. Unfortunately, these treatments have certain drawbacks and complications, including erythema, dryness, and skin peeling, and they take time to work, necessitating the use of herbal formulations for the management of hyperpigmentation. Bioactive compounds isolated from plants, such as arbutin, aloesin, flavonoids, hesperidin, licorice, ellagic acids, genistein, and quercetin, inhibit melanogenesis without melanocytotoxicity by different mechanisms. This review provides information on natural bioactive compounds used for the management of melasma.
Reactive oxygen species (ROS) generated during melanogenesis make melanocytes particularly vulnerable to oxidative stress, influencing their survival and melanin synthesis. Oxidative stress, significantly present in vitiligo and recently also detected in melasma, triggers inflammatory cascades and melanogenesis, making antioxidants a promising therapeutic avenue. A systematic search was conducted on Embase and Pubmed to study the efficacy of antioxidants for treating vitiligo and/or melasma. Meta-analysis was performed to assess the difference in Melasma Severity Index (MASI) scores between baseline and follow-up. Various antioxidants like polypodium leucotomos, ginkgo biloba, catalase/superoxide dismutase, and vitamin E have potential in vitiligo. For melasma, vitamin C, silymarin, and niacinamide were among those showing promise in reducing pigmentation, with vitamin C displaying significant effects in meta-analysis. Different antioxidants improve both vitiligo and melasma, with an increased minimal erythema dose (MED) following UV exposure being significant for vitiligo and tyrosinase inhibition being crucial for melasma. However, the efficacy of individual antioxidants varies, and their exact mechanisms, especially in stimulating melanocyte proliferation and anti-inflammatory pathways, require further investigation to understand better and optimize their use.
Melasma is a common acquired pigmentary disorder predominantly affecting women of childbearing age and Fitzpatrick skin types IV–VI. It negatively impacts the quality of life due to its chronic and relapsing nature. It occurs due to a complex interplay between genetics, hormonal influences, inflammation, oxidative stress, and chronic photodamage. Therefore, a multimodality approach is essential for its treatment. It encompasses photoprotection, topical and oral therapy, and various procedures such as chemical peels, microneedling, lasers, and light treatment. The gold-standard treatment remains topical modified Kligman’s formula, consisting of hydroquinone, corticosteroid, and retinoid, in different concentrations. However, it may cause various adverse effects due to its unsupervised and chronic use. Therefore, novel treatment modalities should not only focus on reducing melanin synthesis and other influencing factors but also have a high safety profile. Among them, botanicals or plant-based extracts have gained massive popularity in the recent past. These compounds have been investigated extensively for their therapeutic activity against pigmentation, efficacy, and safety. Currently, they act as adjuncts to existing topicals. However, there is a paucity of data for their use as monotherapy. This review focuses on newer as well as existing botanicals for the treatment of melasma. Data extraction was done by searching words like botanicals, plant extracts, melasma, and depigmenting agents in databases: Pubmed, Google Scholar, Scopus, and others over the last 20 years.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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