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Saponified Evening Primrose Oil Reduces Melanogenesis in B16 Melanoma Cells and Reduces UV-Induced Skin Pigmentation in Humans
Abstract
This study was conducted to determine whether saponified evening primrose oil (sap-EPO) has the potential for use as a whitening agent and to investigate its underlying mechanisms of action. In B16 melanoma cells, sap-EPO dose-dependently inhibited isobutylmethylxanthine-induced melanogenesis with no cytotoxicity. This decrease in melanin production was correlated with reduced enzyme activity and decreased mRNA and protein levels of tyrosinase. The mRNA levels of tyrosinase-related proteins 1 and 2 decreased in response to treatment with sap-EPO, indicating that it regulated tyrosinase at the transcriptional level. Expression of microphthalmia-associated transcription factor was also decreased by sap-EPO as evidenced by decreased mRNA and protein levels. Additionally, topical application of sap-EPO resulted in efficient whitening of UVB-induced hyperpigmentation of human skin. Taken together, these results suggest that sap-EPO has the potential for use as a cosmetic whitening agent.
... For example, kojic acid is cytotoxic and associated with side-effects such as dermatitis. Ascorbic acid has very low stability (Draelos, 2007;Kim et al., 2008c;Koo et al., 2010). An ideal whitening agent should be safe and stable as well as inhibit melanogenesis without side-effects. ...
... Arbutin, kojic acid, hydroquinone, and ascorbic acid have been used to treat hyperpigmentation disorders. However, the use of these agents is limited due to their side-effects or instability (Draelos, 2007;Koo et al., 2010). ...
... The tyrosinase gene family responsible for the regulation of melanogenesis consists of tyrosinase, TRP-1, and TRP-2. Tyrosinase is a key enzyme involved in melanogenesis and catalyzes the hydroxylation of L-tyrosinase to DOPA and the oxidation of DOPA to DOPA quinone (Koo et al., 2010;Park et al., 2011). TRP-1 and TRP-2 are enzymes that belong to the tyrosinase family and regulate melanogenesis. ...
Lipoteichoic acid (LTA) is a major component of the cell wall of Gram-positive bacteria. Its effects on living organisms are different from those of lipopolysaccharide (LPS) found in Gram-negative bacteria. LTA contributes to immune regulatory effects including anti-aging. In this study, we showed that LTA isolated from Lactobacillus plantarum (pLTA) inhibited melanogenesis in B16F10 mouse melanoma cells. pLTA reduced the cellular activity of tyrosinase and the expression of tyrosinase family members in a dose-dependent manner. The expression of microphthalmia-associated transcription factor (MITF), a key factor in the synthesis of melanin, was also decreased by pLTA. Further, we showed that pLTA activated melanogenesis signaling, such as extra cellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinse (PI3K)/AKT. In addition, the expression of heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and HuR, which are important RNA-binding proteins (RBPs), was reduced. pLTA likely degrades MITF via regulation of melanogenic signaling and RNA stability of melanogenic proteins, resulting in the reduction of melanin. Thus, our data suggest that pLTA has therapeutic potential for treating hyperpigmentation disorders and can also be used as a cosmetic whitening agent.
... Melanin content measurement. The melanin contents of the cultured B16 cells were measured as described previously (18). The cells were washed twice with phosphate-buffered saline (PBS) and lysed with 20 mM Tris-0.1% Triton X-100 (pH 7.5). ...
... Tyrosinase activity assay. Tyrosinase activity was assayed as DOPA oxidase activity with some modifications, as described previously (18). Briefly, cell lysate was obtained after washing twice with PBS. ...
... Safety following long-term application is a very important issue for therapeutic compounds. In recent years, naturally occurring herbal extracts and flavonoids have gained attention as putative hypopigmenting agents (18,(25)(26)(27). In the case of guggulsterone, no toxicity was observed after oral administration (75 mg/kg) for eight weeks in laboratory rats (28). ...
In the present study, we investigated the effect of guggulsterone on melanogenesis in B16 melanoma cells and elucidated its possible mechanism of action. The effects of guggulsterone on melanogenesis were determined by assaying melanin synthesis and cellular tyrosinase activity in B16/F10 mouse melanoma cells. Guggulsterone dose-dependently inhibited isobutylmethylxanthine (IBMX)-induced melanogenesis and cellular tyrosinase activity with no cytotoxicity. Decreased melanin biosynthesis was accompanied by the reduced expression of melanogenesis-related genes, such as tyrosinase, microphthalmia-associated transcription factor, tyrosinase-related protein (TRP)-1 and TRP-2. Guggulsterone also inhibited α-melanocyte stimulating hormone- or forskolin-induced increases in melanogenesis, suggesting an action on the cAMP-dependent melanogenic pathway. Co-incubation with chenodeoxycholic acid, a well-known farnesoid-X receptor agonist, did not affect IBMX-induced melanogenesis. These results suggest that guggulsterone exerts a melanogenic inhibitory effect through the downregulation of tyrosinase expression.
... Vc is a vital reducing agent that can avoid reactions from dopamine to levodopa by regulating the chemical reduction of dopamine [33] and could suppress melanin production via inhibiting tyrosinase activity [34]. Moreover, a study has shown that saponified evening primrose oil effectively inhibited tyrosinase activity, which is consistent with our result [35]. The whitening effect of NC89 and BS4 was studied by a tyrosinase inhibition experiment. ...
... The results in this study show that tobacco seed oil can suppress the production of melanin, showing the potential whitening ability of plant oil. Our finding was also supported by another study, where saponified evening primrose oil effectively reduced melanogenesis in B16 melanoma cells and decreased pigmentation in UV-exposed skin [35]. Values are presented as the mean ± SD (n = 3). ...
Tobacco seeds are a valuable food oil resource, and tobacco seed oil is rich in nutrients, especially polyunsaturated fatty acids. The aim of this work was to perform a comprehensive study on the chemical constituents, and the antioxidant, anti-inflammatory, and whitening activities of tobacco seed oils (NC89 and BS4). A GC/MS analysis revealed that NC89 and BS4 had 11 and 6 volatile compounds, respectively. The PUFA contents in NC89 and BS4 were 74.98% and 72.84%, respectively. These two tobacco seed oils also presented good radical scavenging capacities with the neutralization of ABTS, OH−, and superoxide (O2−) radicals in a concentration-dependent manner. Meanwhile, NC89 and BS4 inhibited reactive oxygen species (ROS) accumulation and cell apoptosis, enhanced SOD and CAT activities, and increased the GSH content in H2O2-induced HepG2 cells. In addition, NC89 and BS4 exhibited significant anti-inflammatory activities by inhibiting the expressions of NO, TNF-α, IL-1β, and IL-6 in LPS-induced RAW.264.7 cells through the regulation of the MAPK signaling pathway. Moreover, NC89 and BS4 expressed whitening activities by inhibiting tyrosinase activity and intracellular melanin production. Therefore, tobacco seed oils could be used as an important oil resource for the development of high value-added products.
... OBO seemed to act as an enhancer of the antioxidant activity of the two vitamins [70]. In addition, Koo et al. demonstrated the whitening effect of saponified OBO of UVB-induced hyperpigmentation on human skin and the anti-melanogenic activity on B16 melanoma cells, due to the increased levels of linoleic acid released by saponification [71]. Timonszuk et al. described that due to their high content of omega-6 acids (mainly linoleic acid and γ-linolenic acid) OBO may influence the inflammatory diseases, including skin problems [29]. ...
The present study was aimed to evaluate the oxidative stability as well as to assess the protective effect of the mixture of Helianthus annuus L. (HAO) and Oenothera biennis L. (OBO) oils on 3D tissue models of skin irritation and phototoxicity. The following methods were used: GS analysis (fatty acids composition), thiobarbituric acid-reactive substances assay (TBA) (lipid oxidation degree of tested samples), 3D EpiDerm models (skin irritation and phototoxicity). For HAO the detected saturated fatty acids (SFA) were palmitic acid (7.179%), stearic acid (3.586%), eicosanoic (0.138%) and docosanoic acid (0.548%) The monounsaturated acids (MUFA) were palmitoleic acid (0.158%) and oleic acid (28.249%) and the polyunsaturated acids (PUFA) were linoleic acid (59.941%) and linolenic acid (0.208%). For OBO the detected SFA were myristic acid (0.325%), pentadecylic acid (0.281%), palmitic (7.2%), stearic (2.88%), and arachidic acid (0.275%). Regarding MUFA, even a lower proportion (8.196%) was observed, predominantly being oleic acid, cis form (7.175%), oleic (n10) (0.558%) and 11-eicosenoic (0.210%) acids. The higher content was found for PUFA (82.247%), the most significant proportions being linoleic acid (72.093%), arachidonic acid (9.812%) and linolenic (0.233%). Obtained data indicate a good oxidative stability and biocompatibility of the mixture on the 3D EpiDerm models with no irritant and no phototoxic effects. Oenothera biennis L. oil may be an excellent natural choice in order to delay or prevent oxidative damage of Helianthus annuus L. oil.
... ex Link, and O. tetraptera Cav., can be found in Taiwan [21]. Plants of the Oenothera genus are known to have a variety of biological activities [23], such as antioxidant [24,25], antiinflammatory [26,27], anti-microbial [28], anti-viral [29], vasorelaxative [30], anti-aging [31], anti-melanogenic [32], and anti-tumor [33,34] activities. O. laciniata has been used as a traditional medicine for inflammatory complications in Taiwan. ...
Oenothera laciniata Hill is a perennial herb traditionally used to alleviate inflammatory complications. This study investigated the antioxidant and anti-melanogenic activities of O. laciniata. The methanolic extract (OLM) of O. laciniata and its different fractions, including ethyl acetate (OLEF), n-butanol (OLBF), and water (OLWF) fractions, were prepared. Antioxidant activities were evaluated by total phenolic content, the radical-scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH•), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+•), and superoxide anion (O2−•), reducing capacity, and metal chelating ability. OLM and its fractions exhibited potent antioxidant activity in these in vitro assays, with a correlation between radical-scavenging activity and total phenolic content. OLM and its fractions inhibited the mushroom tyrosinase activity superior to the reference control, ascorbic acid. In B16-F10 melanoma cells, OLM and its fractions significantly decreased melanin production and tyrosinase activity. Mechanistic investigations revealed that OLM and its fractions inhibited tyrosinase and TRP-2 expressions via downregulating MITF and phosphorylated CREB and differentially inducing ERK or JNK phosphorylation. Additionally, OLM and its fractions caused no significant cytotoxicity towards B16-F10 or skin fibroblast cells at concentrations used in these cellular assays. These findings demonstrated the potential of O. laciniata extracts as the ideal skin protective agent with dual antioxidant and anti-melanogenic activities.
... An essential component of evening primrose oil is gamma-linolenic acid, which was reported to inhibit the growth of B16 melanoma cells [60]. Trying to find natural bleaching agents, Koo et al. demonstrated that saponified evening primrose oil can dose-dependently decrease melanin production, in the case of B16 melanoma cells, via a mechanism that involves a reduction in the activity of enzymes, as well as a decrease in mRNA and protein levels of tyrosinase [61]. Additionally, Kim et al. showed the significant anti-melanogenic potential of O. laciniata methanol extract on melan-a cells, referring to the same mechanism that suppresses tyrosinase activity, tyrosinase-related proteins (TRP-1 and TRP-2) and microphthalmia-associated transcription factor-M mARN expression [30]. ...
Oenothera biennis L. (OB), also commonly known as evening primrose, belongs to the Onagraceae family and has the best studied biological activity of all the members in the family. In therapy, the most frequently used type of extracts are from the aerial part, which are the fatty oils obtained from the seeds and have a wide range of medicinal properties. The aim of this study was to evaluate the phytochemical composition and biological activity of OB hydroalcoholic extract and to provide directions for the antimicrobial effect, antiproliferative and pro-apoptotic potential against A375 melanoma cell line, and anti-angiogenic and anti-inflammatory capacity. The main polyphenols and flavonoids identified were gallic acid, caffeic acid, epicatechin, coumaric acid, ferulic acid, rutin and rosmarinic acid. The total phenolic content was 631.496 µgGAE/mL of extract and the antioxidant activity was 7258.67 μmolTrolox/g of extract. The tested extract had a mild bacteriostatic effect on the tested bacterial strains. It was bactericidal only against Candida spp. and S. aureus. In the set of experimental conditions, the OB extract only manifested significant antiproliferative and pro-apoptotic activity against the A375 human melanoma cell line at the highest tested concentration, namely 60 μg/mL. The migration potential of A375 cells was hampered by the OB extract in a concentration-dependent manner. Furthermore, at the highest tested concentration, the OB extract altered the mitochondrial function in vitro, while reducing the angiogenic reaction, hindering compact tumor formation in the chorioallantoic membrane assay. Moreover, the OB extract elicited an anti-inflammatory effect on the experimental animal model of ear inflammation.
... However, many existing chemical inhibitors of tyrosinase have restricted uses because of side-effects or low stability. For example, kojic acid is cytotoxic and associated with side-effects such as dermatitis, while ascorbic acid has very low stability (Draelos, 2007;Koo et al., 2010). ...
Abnormal accumulation of melanin causes unaesthetic hyperpigmentation. Many studies suggest that yogurt have some effects of antioxidant and anti-aging. In this study, the antioxidant and melanogenesis-inhibitory activity of fermented milk supernatant (FMS) prepared by Lactobacillus plantarum CGMCC8198, a novel probiotics strain, were detected. The results in both ABTS and DPPH assay showed that FMS exhibited markedly antioxidant effect. Melanin production was significantly reduced by FMS, while the survival of cells was not affected. Furthermore, FMS reduced the activity of cellular tyrosinase but had no effect on tyrosinase itself, and the results of RT-PCR, Western blot and immunocytochemistry demonstrated that FMS could inhibit the transcription and expression of tyrosinase, TRP-1, TRP-2 and MITF, and these effects were mainly depended on heated-resistant macromolecule substances. Our results suggested that Lactobacillus plantarum CGMCC8198-Fermented Milk could be a good candidate for antioxidant and treating hyperpigmentation disorders and could also be used as a cosmetic whitening agent.
... It also leads to DNA damage by increasing the production of reactive oxygen species and the development of exogenous ochronosis in mammalian cells [17,18]. Other well-known tyrosinase inhibitors such as Kojic acid and ascorbic acid not only have poor skin penetration, stability, and whitening efficacy but also can cause cytotoxicity, dermatitis, and erythema from long-term use [19,20]. In this regard, there is an increasing need to develop safer and more effective whitening agents for treating human skin hyperpigmentation. ...
Gomisin N, one of the lignan compounds found in Schisandra chinensis has been shown to possess anti-oxidative, anti-tumorigenic, and anti-inflammatory activities in various studies. Here we report, for the first time, the anti-melenogenic efficacy of Gomisin N in mammalian cells as well as in zebrafish embryos. Gomisin N significantly reduced the melanin content without cellular toxicity. Although it was not capable of modulating the catalytic activity of mushroom tyrosinase in vitro, Gomisin N downregulated the expression levels of key proteins that function in melanogenesis. Gomisin N downregulated melanocortin 1 receptor (MC1R), adenylyl cyclase 2, microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). In addition, Gomisin N-treated Melan-A cells exhibited increased p-Akt and pERK levels, which implies that the activation of the PI3K/Akt and MAPK/ERK pathways may function to inhibit melanogenesis. We also validated that Gomisin N reduced melanin production by repressing the expression of MITF, tyrosinase, TRP-1, and TRP-2 in mouse and human cells as well as in developing zebrafish embryos. Collectively, we conclude that Gomisin N inhibits melanin synthesis by repressing the expression of MITF and melanogenic enzymes, probably through modulating the PI3K/Akt and MAPK/ERK pathways.
... No erythema was observed during the sap-EPO treatment. [112] Morning sun protection factor (SPF) 15 Regarding the 75% mulberry extract oil safety profile, only mild itching was reported in four patients, and interestingly, 12 patients reported either itching or erythema from the placebo group [81]. Mulberry extract has been considered as a safe whitening skin agent. ...
... Obniżał on także ekspresję czynnika transkrypcyjnego związanego z mikroftalmią (MITF), co dodatkowo potwierdza działanie na poziomie mRNA i syntezy białek. Miejscowe zastosowanie SAP-EPO powodowało skuteczne rozjaśnianie przebarwień ludzkiej skóry wywołanych ekspozycją na UVB [31]. Ziołem i jednocześnie rośliną o szerszym znaczeniu gospodarczym jest krokosz barwierski (Carthamus tinctorius). ...
Streszczenie Składniki wybielające skórę są obecne w wielu roślinach, grzybach i bakteriach. Stanowią one cel wielu badań w przemyśle kosmetycznym. Obok ekstraktów o działaniu wybielającym, stosowane są czyste substancje aktywne pochodzenia naturalnego lub poszukiwane są związki syntetyczne o ta-kim działaniu. Działanie większości substancji sprowadza się do zakłócenia procesów melanogene-zy, tylko nieliczne substancje mają aktywność rozkładu melaniny. Wstęp W wielu kulturach pojmowanie piękna wiąże się nie tylko z młodą i jędrną, ale tak-że z jasną i pozbawioną zmian pigmentacyjnych, nieskazitelną skórą. Przebarwienia skórne w wielu kulturach (szczególnie azjatyckich) mogą stanowić problem natury es-tetycznej, a często także i psychologicznej [42]. Skłania to do poszukiwania składników kosmetyków mogących pomóc w zapobieganiu powstawania przebarwień lub w ich usuwaniu. Taki efekt można uzyskać unikając czynników sprzyjających powstawaniu przebarwień, np. promieni słonecznych, lub sięgając do tego, czym dysponuje współ-czesna branża kosmetyczna. Obecnie kosmetologia dysponuje dość szerokim wachla-rzem komponentów rozjaśniających skórę, ale wciąż są poszukiwane nowe, zwłasz-cza takie, które w bezpieczny i prosty sposób zlikwidują plamy i przebarwienia.
... For example, to increase polyphenol concentration in the large intestine, one can administer them in the form of pills made of polymers that undergo hydrolysis in the presence of bacterial glycosidases (e.g., guar gum, chondroitin sulfate, pectin, starch, amylose, dextran, chitosan, inulin) (34).Taking into account the role ascribed to phenolic compounds as chemopreventive and anticancer agents, we decided to study an extract from evening primrose seeds in that respect. Although there are numerous reports on the health-beneficial effects of evening primrose seed oil (35,36), the knowledge on biological activities of polyphenols (including flavanols) isolated from defatted seeds of evening primrose is still scarce (11,37,38). We started with the determination of the influence of procyanidin-and catechinrich EPFP on the viability of highly invasive breast cancer cells (MDA-MB-231). ...
There is a growing interest in plant polyphenols (including flavanols) that exhibit pleiotropic biological activities such as antiinflammatory, antioxidant, and anticancer effects. Here, we report for the first time the inhibition of MDA-MB-231 breast cancer cell viability and invasiveness by an evening primrose flavanol preparation (EPFP). We observed a decrease in MDA-MB-231 viability of 50% vs. a control after 72 h of incubation with EPFP at a concentration of 58 μM gallic acid equivalents (GAE) and an inhibition of their invasiveness of 65% vs. a control at 75 μM GAE after 48 h of incubation. EPFP caused a 10-fold reduction in matrix metalloproteinase-9 (MMP-9) activity at 100 μM GAE. Furthermore, through modulation of mRNA expression, EPFP reduced the expression levels of the following proteins: antiapoptotic Bcl-2, angiogenic vascular endothelial growth factor (VEGF), and 2 transcription factors (c-Jun, c-Fos). Moreover, analysis by flow cytometry revealed that EPFP induced apoptosis in MDA-MB-231 cells. In conclusion, our data shows that EPFP inhibits cell viability by increasing apoptosis and decreases cell invasiveness by decreasing angiogenesis.
... Saponi�ed Evening Primrose oil (Oenothera biennis) exerts a pigment-whitening effect by inhibiting the expression of tyrosinase and related enzymes; therefore, this effect may be related to the high proportions of Linoleic acid released by saponi�cation from Evening Primrose oil [72]. ...
The fact that the skin is the most visible organ makes us aware of the ageing process every minute. The use of plant extracts and herbs has its origins in ancient times. Chronological and photo-ageing can be easily distinguished clinically, but they share important molecular features. We tried to gather the most interesting evidence based on facts about plants and plant extracts used in antiaging products. Our main idea was to emphasize action mechanisms of these plant/herbal products, that is, their "strategies" in fighting skin ageing. Some of the plant extracts have the ability to scavenge free radicals, to protect the skin matrix through the inhibition of enzymatic degradation, or to promote collagen synthesis in the skin. There are some plants that can affect skin elasticity and tightness. Certainly, there is a place for herbal principles in antiaging cosmetics. On the other hand, there is a constant need for more evaluation and more clinical studies in vivo with emphasis on the ingredient concentration of the plant/herbal products, its formulation, safety, and duration of the antiaging effect.
The increasing demand for natural ingredients in cosmetics raises new challenges for the characterization of highly complex natural extracts and the production of standardized extracts. Metabolomics has spread in a variety of research areas with great success for metabolite identification, product discrimination, and the control of quality, authenticity and adulteration. This review aims to present recent trends in the development of metabolomics tools and their potential to address new issues in natural cosmetics for more effective selection and control of natural ingredients. The current sources of natural ingredients used in skincare products are summarized. The actual metabolomics approaches are delineated, encompassing the pivotal steps of metabolomic workflow from sample extraction and metabolite identification to data mining and statistical analysis. Outlined are diverse cosmeceutical activities, ranging from antioxidant effectiveness and anti-inflammatory potential to rejuvenating properties, ultraviolet radiation protection, and the brightening attributes inherent in natural extracts. Finally, we presented the contributions of metabolomics to the quality assessment of natural cosmetics ingredients by identification of bioactive compounds, dereplication of bio-sourced ingredients, quality and safety assessment of extracts, authentication, and traceability, and the detection of adulteration. This review presents systematic approaches to studying the complex phytochemical mixtures found in natural ingredients, linking analytical techniques to biological assay systems, and thereby opening new opportunities for discovering active principles and assisting in the production of standardized compositions.
The Chemistry inside Spices and Herbs: Research and Development brings comprehensive information about the chemistry of spices and herbs with a focus on recent research in this field. The book is an extensive 2-part collection of 20 chapters contributed by experts in phytochemistry with the aim to give the reader deep knowledge about phytochemical constituents in herbal plants and their benefits. The contents include reviews on the biochemistry and biotechnology of spices and herbs, herbal medicines, biologically active compounds and their role in therapeutics among other topics. Chapters which highlight natural drugs and their role in different diseases and special plants of clinical significance are also included. Part II continues from the previous part with chapters on the treatment of skin diseases and oral problems. This part focuses on clinically important herbs such as turmeric, fenugreek, ashwagandha (Indian winter cherry), basil, Terminalia chebula (black myrobalan). In terms of phytochemicals, this part presents chapters that cover resveratrol, piperine and circumin.
The Chemistry inside Spices & Herbs: Research and Development brings comprehensive information about the chemistry of spices and herbs with a focus on recent research in this field. The book is an extensive 2-part collection of 20 chapters contributed by experts in phytochemistry with the aim to give the reader deep knowledge about phytochemical constituents in herbal plants and their benefits. The contents include reviews on the biochemistry and biotechnology of spices and herbs, herbal medicines, biologically active compounds and their role in therapeutics among other topics. Chapters which highlight natural drugs and their role in different diseases and special plants of clinical significance are also included.
Part II continues from the previous part with chapters on the treatment of skin diseases and oral problems. This part focuses on clinically important herbs such as turmeric, fenugreek, ashwagandha (Indian winter cherry), basil, Terminalia chebula (black myrobalan). In terms of phytochemicals, this part presents chapters that cover resveratrol, piperine and circumin.
Audience: This book is an ideal resource for scholars (in life sciences, phytomedicine and natural product chemistry) and general readers who want to understand the importance of herbs, spices and traditional medicine in pharmaceutical and clinical research.
In the last decades, many unconventional oils have attracted great attention due to higher biological compounds. Evening primrose oil (Oenothera biennis) is commonly utilized as herbal medicine rich in omega-6 essential fatty acids (i.e., linoleic acid and γ-linoleic acid). The positive effect of EPO has been demonstrated in the case of many diseases such as cyclic breast pain, gestational diabetes, inflammations, cancer, dermatitis, kidney problem, rheumatoid arthritis, oxidative stress, and diabetes mellitus. The present chapter aimed to provide currently available literature related to the biological activities of EPO.
In the present study, we demonstrated that borage (Borago officinalis L.) seed oil subjected to immobilized lipase pretreatment are enriched with linoleic acid (LNA, 18:2n‐6), γ‐linolenic acid (GLA, 18:3n‐6), and oleic acid (OLA, 18:1n‐9). We further showed that lipase‐treated borage oil (LT‐BOL) regulates the activity and degradation of tyrosinase, an important enzyme implicated in the synthesis of melanin in murine melanocytes, B16F10. LT‐BOL and its free fatty acid components reduced the levels of melanin and tyrosinase in melanocytes with GLA exerting similar or stronger effects compared with LNA and OLA. The brightening efficacy of LT‐BOL on melanin metabolism in humans was tested by an 8‐week, double‐blind, randomized clinical trial, which enrolled 21 Korean female adults (mean age 48.57 ± 3.28). Visual evaluation showed that cream containing 1% LT‐BOL significantly decreased (p < 0.05) melasma on the treated skin area after 6 and 8 weeks. The analysis of the skin brightness using Chromameter CR‐400 confirmed that the brightness of the treated area was significantly increased (p < 0.01) after 4, 6, and 8 weeks. Together, our results suggest that LT‐BOL may be suitable as a natural skin whitening cosmeceutical product.
Hyperpigmentation of skin is caused by several factors. UV exposure, in addition to oxidative stress elevates inflammatory mediators stimulating melanogenesis. Herbal derived compounds for improving skin lightness are gaining interest as they are perceived to be milder, safer and healthier than fully synthetic products. This review briefly addresses the causes of skin hyperpigmentation and extensively summarizes the status of herbs currently used in skin lightening cosmetics. The properties of active compounds and their dose rate information is summarized where available, along with human or anamial relevant models for activity testing. This review will be of value to cosmetic formulators and dermatologists who are searching for naturally-derived ingredients for improving skin lightness, in line with consumer preference and expectations.
Herbs and spices have been used in retaining
and boosting human beauty since time immemorial.
Herbal cosmetic has growing demand in the worldwide
market and is an invaluable gift of Mother Nature. In
the present review, the focus is on the cosmetic herbs of
Southeast Asian countries namely Malaysia, Cambodia,
Laos, Myanmar [Burma], Thailand, Vietnam,
Brunei, East Timor, Indonesia, Philippines and Singapore
in highlighting both traditional and scientific
knowledge or background of the selected potential
herbs. The available literature was searched in the
following scientific database such as PubMed, Google
Scholar, Science Direct and Springer for publications
and patents. In view of traditional uses, herbs like
Allium sativum, Aloe vera, Centella asiatica, Curcuma
longa, Hibiscus rosa-sinensis, Lawsonia inermis and
Tamarindus indica L. were classified as need of special
mention. Many herbs have been scientifically evaluated
for their cosmetic potentials such as anti-aging, antiacne,
melanogenic and anti-tyrosinase activities. The
great void remains for a systematic study, thorough
review of scientific report that provides a basis for the
use of specific herbs due to their efficacy as cosmetics.
In addition, two of the Malay herbs; Labisia pumila
(Kacip Fatimah) and Ficus deltoidea (Mas cotek), are
proposed to be clinically studied for their safety in
cosmetic application aspects wherein the need for
safety evaluation and fruitful application of herbal
cosmetics were emphasized.
Context:
Sophora flavescens Ait. (Leguminosae) has been proposed as a new whitening agent for cosmetics, because it has a strong ability to inhibit tyrosinase, a key enzyme in the formation of melanin.
Objective:
We conducted a study to determine whether ethanol extract of the roots of S. flavescens has the potential for use as a whitening cosmetic agent by investigating its underlying mechanisms of action.
Materials and methods:
To elucidate the mechanism of action of S. flavescens extract, we used DNA microarray technology. We investigated the changes in the mRNA levels of genes associated with the formation and transport of melanosomes. We also identified the formation and transport of melanosomes with immunohistochemistry and immunofluorescence analyses. Finally, the skin-whitening effect in vivo of S. flavescens extract was analyzed on human skin.
Results:
We found that S. flavescens extract strongly inhibited tyrosinase activity (IC50, 10.4 μg/mL). Results also showed that key proteins involved in the formation and transport of melanosomes were dramatically downregulated at both mRNA and protein level in keratinocytes exposed to S. flavescens extract. In addition, a clinical trial of a cream containing 0.05% S. flavescens extract on human skin showed it had a significant effect on skin whitening by mechanical and visual evaluation (1.14-fold).
Discussion and conclusion:
This study provides important clues toward understanding the effects of S. flavescens extract on the formation and transport of melanosomes. From these results, we suggest that naturally occurring S. flavescens extract might be useful as a new whitening agent in cosmetics.
We have cloned and sequenced the human genomic DNA segments encoding the 5'-flanking region and the first two exons of the DOPAchrome tautomerase (DT)/tyrosinase-related protein 2 (TRP-2) gene. The DT gene is a member of the tyrosinase gene family and specifically expressed in melanin-producing cells. A transcriptional initiation site of the DT gene was identified by S1 nuclease-mapping and primer-extension analyses using RNA prepared from human pigmented melanoma cells. To study the mechanism for pigment cell-specific expression of the human DT gene, we analyzed the promoter function of its 5'-flanking region by transient expression assays. The fusion genes, containing the DT gene promoter upstream from a firefly luciferase reporter gene, were introduced into human pigmented melanoma cells and HeLa cells, and the pigment cell-specific promoter activity was evaluated by comparing the luciferase activity expressed in both cell lines. A series of 5' deletion studies of the human DT gene promoter revealed that the 32-bp element, located between -447 and -415, is sufficient to confer pigment cell-specific expression of a reporter gene on a homologous promoter, but not on a heterologous simian virus 40 promoter. Internal deletion studies using a homologous or a heterologous promoter revealed that the pigment cell-specific expression of a reporter gene mediated by the 32-bp element is dependent on the presence of another region of the DT gene spanning from -268 to -56, which was termed the proximal region. However, the proximal region by itself is not sufficient to confer cell type-specific expression. These results indicate that the presence of two regulatory regions, the 32-bp element and the proximal region, is required for pigment cell-specific expression of the DT gene. Both regulatory regions contain a CANNTG motif, a well known binding site for a large family of transcription factors possessing a basic helix-loop-helix structure.
The purpose of this study was to investigate the mechanism of fatty acid-induced regulation of melanogenesis. An apparent regulatory effect on melanogenesis was observed when cultured B16F10 melanoma cells were incubated with fatty acids, i.e., linoleic acid (unsaturated, C18:2) decreased melanin synthesis while palmitic acid (saturated, C16:0) increased it. However, mRNA levels of the melanogenic enzymes, tyrosinase, tyrosinase-related protein 1 (TRP1), and tyrosinase-related protein 2 (TRP2), were not altered. Regarding protein levels of these enzymes, the amount of tyrosinase was decreased by linoleic acid and increased by palmitic acid, whereas the amounts of TRP1 and TRP2 did not change after incubation with fatty acids. Pulse-chase assay by [35S]methionine metabolic labeling revealed that neither linoleic acid nor palmitic acid altered the synthesis of tyrosinase. Further, it was shown that linoleic acid accelerated, while palmitic acid decelerated, the proteolytic degradation of tyrosinase. These results suggest that modification of proteolytic degradation of tyrosinase is involved in regulatory effects of fatty acids on melanogenesis in cultured melanoma cells.
Melasma is an acquired symmetric hypermelanosis characterized by irregular light-to gray-brown macules and patches on sun-exposed areas. Many therapeutic agents are available but are unsatisfactory. Recently, it has been demonstrated that lincomycin (LM) and linoleic acid (LA) can inhibit melanogenesis in vitro. Our purpose was to investigate the clinical efficacy of topical application of LM and LA in combination with betamethasone valerate (BV) in melasma patients. Forty-seven Korean female adults with clinically diagnosed melasma were enrolled in a 6-week, double-blind, randomized clinical trial. Patients were treated with one application of the vehicle (group A), 2% LM mixed with 0.05% BV (group B), or 2% LM mixed with 0.05% BV and 2% LA (group C) on the face every night. Determination of efficacy was based on the Melasma Area and Severity Index (MASI) score and objective assessment (no effect, mild, moderate, or excellent) at intervals of 2 weeks until the end of the study at 6 weeks. After 6 weeks, in comparison with the pre-treatment MASI score, the average MASI score of group C decreased to 68.9%, compared with 98% in group A (p<0.05) and 85.4% in group B. There was no statistically significant difference between group A and group B. Seven patients (43.7%) in group C revealed more than moderate improvement in objective assessment, compared with none in group A and two patients (12.5%) in group B. There were no significant side effects. Topical application of linoleic acid is considered to be effective in the treatment of melasma patients.
Xanthohumol (XH), the principal prenylflavonoid of the hop plant (Humulus lupulus L.), dose-dependently inhibited isobutylmethylxanthine (IBMX)-induced melanogenesis in B16 melanoma cells, with little cytotoxicity at the effective concentrations. Decreased melanin content was accompanied by reduced tyrosinase enzyme activity, protein and mRNA expression. The levels of tyrosinase-related protein 1 and 2 mRNAs were decreased by XH. XH also inhibited alpha-melanocyte stimulating hormone- or forskolin-induced increases in melanogenesis, suggesting an action on the cAMP-dependent melanogenic pathway. XH downregulated the protein and mRNA expression of microphthalmia-associated transcription factor (MITF), a master transcriptional regulator of key melanogenic enzymes. These results suggest that XH might act as a hypo-pigmenting agent through the downregulation of MITF in the cAMP-dependent melanogenic pathway.
The signalling pathways involved in melanogenesis have been partially elucidated. The role of melanotropin peptides, α-MSH and ACTH, in melanocyte differentiation and in the regulation of melanogenesis is now widely recognized. Their melanogenic effects appear to be mediated through the up-regulation of the cAMP pathway by the melanocortin-1 receptor and the activation of adenylate cyclase. The molecular mechanisms involve the subsequent phosphorylation and activation of PKA, followed by CREB which binds to the promoter of the transcription factor Microphthalmia, and upregulates its transcription. The elevated expression of Microphthalmia increases its binding to the specific E-box and M-box present in the tyrosinase promoter, resulting in an increased expression of this enzyme and the up-regulation of melanin synthesis. LEF-1 and β-catenin also regulate the expression of Microphthalmia and play a key-role in pigment cell differentiation. Other transcription factors such as Brn2, TBX2, PAX3, Sox10 are also involved in these processes. cAMP modulates several other signalling pathways involved in the regulation of melanogenesis. The cAMP-induced melanogenesis and dendricity are partially mediated by the inhibition of the phosphatidylinositol-3-kinase/p70S6 kinase pathway. In addition, cAMP activates a melanocyte-specific pathway leading to MAP kinase activation. These new advances lead to a better understanding of the natural photoprotective mechanisms of the skin. In the future, they should help to the development of treatments for pigmentary disorders, and more efficient prevention strategies against sun-induced carcinogenesis of human skin.
Background:
Melasma is difficult to clear. Many agents have been used, such as hydroquinone, and glycolic acid and glycolic acid peels, kojic acid, a tyrosinase inhibitor in the fungus Aspergilline oryzae.
Objective:
To see if the addition of 2% kojic acid in a gel containing 10% glycolic acid and 2% hydroquinone will improve melasma further.
Methods:
Forty Chinese women with epidermal melasma were treated with 2% kojic acid in a gel containing 10% glycolic acid and 2% hydroquinone on one half of the face. The other half was treated with the same application but without kojic acid. The side receiving the kojic acid was randomized. Determination of efficacy was based on clinical evaluation, photographs and self-assessment questionnaires at 4 weekly intervals until the end of the study at 12 weeks. The non-parametric Wilcoxon's rank sum test was used for statistical analysis.
Results:
All patients showed improvement in melasma on both sides of the face. The side receiving the kojic acid did better. More than half of the melasma cleared in 24/40 (60%) patients receiving kojic acid compared to 19/40 (47.5%) patients receiving the gel without kojic acid. In 2 patients, there was complete clearance of melasma, and this was on the side where kojic acid was used. Side effects include redness, stinging, and exfoliation. These were seen on both sides of the face, and they settled by the third week.
Conclusion:
The addition of kojic acid to a gel containing 10% glycolic acid and 2% hydroquinone further improves melasma.
Abstract This study was conducted to evaluate the effects of unsaturated fatty acids on ultraviolet-induced hyperpigmentation of the
skin. An efficient lightening effect was observed following topical application of linoleic acid or α-linolenic acid to UV-stimulated
hyperpigmented dorsal skin of brownish guinea pigs. The number of melanocytes in the treated skin was similar to the number
in the skin of the pigmented control, indicating that the pigment-lightening effect was not due to depletion of melanocytes.
In vitro experiments using cultured murine melanoma cells showed that melanin production was inhibited most effectively by
α-linolenic acid, followed by linoleic acid and then by oleic acid. Furthermore, the turnover of the stratum corneum, which
plays an important role in the removal of melanin pigment from the epidermis, was accelerated by linoleic acid and by α-linolenic
acid. Taken together, the results suggest that the pigment-lightening effects of linoleic acid and α-linolenic acid are, at
least in part, due to suppression of melanin production by active melanocytes, and to enhanced desquamation of melanin pigment
from the epidermis.
A protein determination method which involves the binding of Coomassie Brilliant Blue G-250 to protein is described. The binding of the dye to protein causes a shift in the absorption maximum of the dye from 465 to 595 nm, and it is the increase in absorption at 595 nm which is monitored. This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr. There is little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose. A small amount of color is developed in the presence of strongly alkaline buffering agents, but the assay may be run accurately by the use of proper buffer controls. The only components found to give excessive interfering color in the assay are relatively large amounts of detergents such as sodium dodecyl sulfate, Triton X-100, and commercial glassware detergents. Interference by small amounts of detergent may be eliminated by the use of proper controls.
1. Tyrosinase is a copper-containing enzyme responsible for the production of melanin pigment throughout the phylogenetic spectrum. 2. In mammals, tyrosinase is a glycosylated enzyme found specifically in melanocytes--cells functional in the production and secretion of pigment granules. 3. Although many factors determine the type, quantity and quality of the melanin produced, tyrosinase activity is the critical factor that ultimately regulates melanogenesis.
There have been reports that certain dietary lipids are capable of regulating cellular inflammation and hyperproliferation. To investigate further the role of dietary manipulation involving γ-linolenic acid (18:3n-6) and eicosapentaenoic acid (20:5n-3) on hyperproliferative cellular components, the effects of orally administered primrose oil (containing 18:3n-6) and menhaden fish oil (containing 20:5n-3) were tested in a cutaneous system using the essential fatty acid (EFA)–deficient guinea pig fed a hydrogenated coconut oil (HCO) diet. The effects of the dietary crossover regimen were determined on epidermal
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morphology,
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DNA synthesis,
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Δ⁶- and Δ⁵-desaturase activities and
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fatty acid composition of skin and liver lipids.
Our results demonstrated that dietary fish oil lacked the capacity to reverse the signs of epidermal hyperproliferation, acanthosis and hypergranulosis that are characteristic of EFA deficiency. In contrast, primrose oil feeding reversed the histological and biochemical signs of hyperproliferation. These results suggest that dietary fish oil, which contains largely the 20:5n-3 fatty acid, lacks EFA-functional properties in the skin. In addition, substitution of HCO with primrose or fish oil after 6 wk revealed incorporation of 18:3n-6 and 20:5n-3 into epidermal lipids, respectively. The significance of these altered epidermal fatty acid profiles is discussed.
Several genes critical to the enzymatic regulation of melanin production in mammals have recently been cloned and mapped to the albino, brown and slaty loci in mice. All three genes encode proteins with similar structures and features, but with distinct catalytic capacities; the functions of two of those gene products have previously been identified. The albino locus encodes tyrosinase, an enzyme with three distinct melanogenic functions, while the slaty locus encodes tyrosinase-related protein 2 (TRP2), an enzyme with a single specific, but distinct, function as DOPAchrome tautomerase. Although the brown locus, encoding TRP1, was actually the first member of the tyrosinase gene family to be cloned, its catalytic function (which results in the production of black rather than brown melanin) has been in general dispute. In this study we have used two different techniques (expression of TRP1 in transfected fibroblasts and immunoaffinity purification of TRP1 from melanocytes) to examine the enzymatic function(s) of TRP1. The data demonstrate that the specific melanogenic function of TRP1 is the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) to a carboxylated indole-quinone at a down-stream point in the melanin biosynthetic pathway. This enzyme activity appears to be essential to the further metabolism of DHICA to a high molecular weight pigmented biopolymer.
Arbutin, a naturally occurring beta-D-glucopyranoside of hydroquinone, is effective in the topical treatment of various cutaneous hyperpigmentations characterized by hyperactive melanocyte function. We examined the mechanism of its depigmenting action in human melanocyte cultures. Arbutin inhibited the tyrosinase activity of cultured human melanocytes at noncytotoxic concentrations. It did not affect the expression of tyrosinase mRNA. Melanin production was inhibited significantly by arbutin, as determined by measuring eumelanin radicals with an electron spin resonance spectrometer. The study of the kinetics and mechanism for inhibition of tyrosinase confirms the reversibility of arbutin as a competitive inhibitor of this enzyme. The utilization of L-tyrosine or L-dopa as the substrate suggests a mechanism involving competition with arbutin for the L-tyrosine binding site at the active site of tyrosinase. These results suggest that the depigmenting mechanism of arbutin in humans involves inhibition of melanosomal tyrosinase activity, rather than suppression of the expression and synthesis of tyrosinase.
Compelling evidence has been gathered indicating that pro-opiomelanocortin peptides, alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH), through the cyclic AMP pathway, play a pivotal role in melanocyte differentiation and in the regulation of melanogenesis. Recently, the molecular events linking cAMP to melanogenesis up-regulation have been elucidated. This cascade involves the activation of protein kinase A and CREB transcription factor, leading to the up-regulation of the expression of Microphthalmia associated transcription factor (MITF). MITF has been found mutated in patients with Waardenburg syndrome 2A, and plays a crucial role in melanocyte development. MITF binds and activates melanogenic gene promoters, thereby increasing their expression which results in an increased melanin synthesis. Beyond this simplified scheme, It appears that melanogenic gene expression is controlled by a complex network of regulation involving other transcription factors such as Brn2, TBX2, PAX3 and SOX10. Further studies are required to better understand the respective roles of these factors in the regulation of melanin synthesis. In addition, other intracellular signaling pathways, like the phosphatidyl inositol 3-kinase pathway, as well as the molecular cascade of events governed by the small GTP-binding protein Rho, seem to be involved in the regulation of melanogenesis and melanocyte dendricity. Finally, it should be mentioned that cAMP activates a melanocyte-specific pathway leading to MAP kinase activation. MAP kinase, ERK2, phosphorylates MITF, thereby targeting the transcription factor to proteasomes for degradation. Thus, in addition to the complex transcriptional regulation, melanogenesis is also subjected to a post-translational regulation that controls MITF or tyrosinase function. Taken together, these complex molecular processes would finally allow a fine tuning of melanocyte differentiation leading to melanin synthesis.
Microphthalmia-associated transcription factor (MITF) is a transcription factor with a basic-helix-loop-helix-leucine zipper (bHLHZip) structure. Mutations of the MITF gene cause a variety of phenotypes, most notably in pigmented cells, in several species. In humans, haploinsufficiency of MITF causes Waardenburg syndrome type 2, while a dominant-negative mutation causes Tietz syndrome. Four isoforms have been cloned so far: MITF-M is the most abundant and is expressed in neural-crest-derived melanocytes; MITF-A is expressed in various cultured cells including retinal pigment epithelium (RPE) and enriched in RPE of embryonal and developing eyes; MITF-H are expressed in many types of cultured cells and in the heart tissue; MITF-C is expressed in many types of cultured cells, but not in melanocytes. Many growth factor signaling pathways have been implicated for regulation of MITF at both protein and promoter levels. Most notably, Steel factor/c-Kit signaling pathway was linked to phosphorylation of MITF at Ser73 and Ser409 through activation of MAP kinase and RSK-1, respectively. Phosphorylation of MITF is also conducted at Ser298 through GSK3beta, although the signaling pathway for this event still remains to be elucidated. IGF-1 and HGF/SF pathways may merge with the c-Kit signaling pathway. WNT and MSH signaling pathways regulate MITF positively at the promoter level. Endothelins may regulate MITF at the protein and promoter levels. MITF is involved in the differentiation, growth and survival of pigment cells, employing a number of signaling pathways.
Linoleic acid (LA) is known to have a whitening effect on hyperpigmented skin, and is encapsulated in liposomes for topical application because of its low solubility in aqueous solution, although the effect of liposomalization of LA on the whitening activity has not been evaluated. In the present study, we evaluated the effect of liposomalization on the whitening activity of LA by using LA in ethanol, hydrogel containing LA, and hydrogel containing liposomal LA towards the UV-stimulated hyperpigmented dorsal skin of brownish guinea pigs. The whitening effect was far greater for hydrogel containing liposomal LA (0.1% w/w as a final concentration of LA) than for free LA in ethanol or hydrogel containing LA. Next, the whitening effect of LA was examined with UV-stimulated hyperpigmented human upper arm skin by using a hydrogel containing liposomal LA (0.1% LA) and non-liposomal LA (3.0, 10.0% LA). Liposomal LA (0.1%) showed a whitening effect comparable to 10.0% non-liposomal LA and was far more effective than 3.0% non-liposomal LA. These results indicate that liposomal formulations are favorable for the transdermal application of LA.
Microphthalmia-associated transcription factor (MITF) acts as a master regulator of melanocyte development, function and survival by modulating various differentiation and cell-cycle progression genes. It has been demonstrated that MITF is an amplified oncogene in a fraction of human melanomas and that it also has an oncogenic role in human clear cell sarcoma. However, MITF also modulates the state of melanocyte differentiation. Several closely related transcription factors also function as translocated oncogenes in various human malignancies. These data place MITF between instructing melanocytes towards terminal differentiation and/or pigmentation and, alternatively, promoting malignant behavior. In this review, we survey the roles of MITF as a master lineage regulator in melanocyte development and its emerging activities in malignancy. Understanding the molecular function of MITF and its associated pathways will hopefully shed light on strategies for improving therapeutic approaches for these diseases.
The effect of coumarin derivatives on melanogenesis was investigated in B16 murine melanoma cells.
Melanin content and tyrosinase activity were analyzed spectrophotometrically. The expression of tyrosinase, tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2) were measured either by reverse transcription-polymerase chain reaction (RT-PCR) or Western blot.
Among the coumarin derivatives studied, scoparone (6,7- dimethoxycoumarin) was the most potent; the 6- or 7-methoxy group was found to be essential for the stimulation of melanogenesis. The melanin content was greatly increased by scoparone in a dose-dependent manner; there was no cytotoxicity at the effective concentrations. Scoparone increased enzyme activity as well as protein and mRNA expression of tyrosinase. In addition, mRNA of TRP-1 and TRP-2 were also increased after treatment with scoparone. H-89, an inhibitor of protein kinase A (PKA), completely inhibited the scoparone-induced increase of melanogenesis and the tyrosinase protein.
These results suggest that scoparone-induced stimulation of melanogenesis is likely to occur at the transcriptional level of melanogenesis-related enzymes through PKA signaling.
Melanocytes are phenotypically prominent but histologically inconspicuous skin cells. They are responsible for the pigmentation of skin and hair, and thereby contribute to the appearance of skin and provide protection from damage by ultraviolet radiation. Pigmentation mutants in various species are highly informative about basic genetic and developmental pathways, and provide important clues to the processes of photoprotection, cancer predisposition and even human evolution. Skin is the most common site of cancer in humans. Continued understanding of melanocyte contributions to skin biology will hopefully provide new opportunities for the prevention and treatment of skin diseases.
During the screening of herbs for inhibition of melanogenesis, it was observed that ethanolic extract of Angelicae Gigantis Radix (AGE) effectively inhibited isobutylmethylxanthine-induced melanogenesis in B16 melanoma cells. The melanin content was significantly decreased by AGE in a dose-dependent manner, and no cytotoxicity was observed at the effective concentrations. Decreased melanin content was accompanied by reduced enzyme activity as well as reduced expression of tyrosinase protein and mRNA. The level of tyrosinase-related protein 1 and 2 mRNAs was also decreased by AGE. Additionally, AGE effectively inhibited alpha-melanocyte stimulating hormone- and forskolin-induced melanogenesis, and downregulated the mRNA expression of microphthalmia-associated transcription factor, a master transcriptional regulator of melanogenic genes. These results suggest that AGE acts as a putative hypopigmenting agent through downregulation of tyrosinase expression induced via a cAMP-dependent pathway.
Skin lightening preparations are widely used in dermatology by persons of all Fitzpatrick skin types. Fitzpatrick skin types I-III require local pigment lightening for the treatment of hormonally induced melasma and postinflammatory hyperpigmentation caused by acne and trauma. Fitzpatrick skin types IV and darker have an even greater need for skin lightening for social reasons, as well as pigmentary changes that occur around the eyes, in the intertriginous areas, following dermatitis, or with acne and trauma. The gold standard dermatologic agent for skin lightening was hydroquinone, until regulatory agencies in Japan, Europe, and most recently in the United States questioned the safety of this substance. This has encouraged research into alternative agents to inhibit skin pigmentation such as retinoids, mequinol, azelaic acid, arbutin, kojic acid, aleosin, licorice extract, ascorbic acid, soy proteins, and N-acetyl glucosamine. The efficacy and safety of each of these ingredients is examined as possible topical alternatives to hydroquinone.
The oil obtained from the evening primrose (Oenothera biennis) plant is usually taken orally in a gel cap form. This herbal supplement is most commonly used for the treatment of mastalgia and atopic dermatitis. While recommending this supplement to patients for many years for the treatment of mastalgia, this author was interested in researching the plant and the evidence supporting its use for this complaint and its other potential uses. The oil is rich in omega-6 fatty acids, which are essential for many bodily functions; however, a lack of strong scientific evidence exists to support its use for the relief of mastalgia or atopic dermatitis.
Recently melanogenic paracrine or autocrine cytokine networks have been discovered in vitro between melanocytes and other types of skin cells. These include endothelin (ET)-1, granulocyte macrophage colony stimulating factor, membrane-type stem cell factor (SCF) and growth-related oncogene-alpha for interactions between keratinocytes and melanocytes, and hepatocyte growth factor and soluble type SCF for interactions between fibroblasts and melanocytes. These networks are also associated with corresponding receptors expressed on melanocytes, including ET B receptor and the SCF receptor, c-KIT. Consistent with in vitro findings on the melanogenic paracrine or autocrine cytokine networks, we have found that the up- or down-regulation of such networks is intrinsically involved in vivo in the stimulation of melanocyte functions in several epidermal hyper- or hypo-pigmentary disorders. These are ET-1/ET B receptor as well as membrane type SCF/c-KIT for ultraviolet B-melanosis, granulocyte macrophage colony stimulating factor for ultraviolet A-melanosis, ET-1/ET B receptor as well as membrane type SCF for lentigo senilis, growth related oncogene-alpha for Riehl's melanosis, sphingosylphosphorylcholine for hyperpigmentation in atopic dermatitis, ET-1 for seborrhoeic keratosis, soluble type SCF as well as hepatocyte growth factor for dermatofibroma and café-au-lait macules, and c-KIT for vitiligo vulgaris. These unveiled regulatory mechanisms involved in the abnormal up- or down-regulated levels of lesional melanocyte function provide new insights into therapeutic tools utilizing blockage of responsible cytokine networks.
Melanocyte biology and skin pig-mentation
- Lin Jy Fisher
- De
Lin JY, Fisher DE (2007) Melanocyte biology and skin pig-mentation. Nature 445:843–850
Regulation of melanin formation The pigmentary system: physiology and pathophysiology
- Vj Hearing
- Jj Nordlund
- Re Boissy
- Vj Hearing
- Ra King
The enzymology of melanogenesis The pigmentary system: physiology and pathophysiology
- Jm Pawelek
- Ak Chakraborty
- Jj Nordlund
- Re Boissy
- Vj Hearing
- Ra King
The enzymology of melanogenesis
- J M Pawelek
- A K Chakraborty
Arbutin: mechanism of its depigmenting action in human melanocyte culture
- Maeda K