Phototherapy for vitiligo: A narrative review on the clinical and molecular aspects, and recent literature.

BACKGROUND: Vitiligo is characterized by depigmented patches resulting from loss of melanocytes. Phototherapy has emerged as a prominent treatment option for vitiligo, utilizing various light modalities to induce disease stability and repigmentation. AIMS AND METHODS: This narrative review aims to explore the clinical applications and molecular mechanisms of phototherapy in vitiligo. RESULTS AND DISCUSSION: The review evaluates existing literature on phototherapy for vitiligo, analyzing studies on hospital-based and home-based phototherapy, as well as outcomes related to stabilization and repigmentation. Narrowband ultra-violet B, that is, NBUVB remains the most commonly employed, studied and effective phototherapy modality for vitiligo. Special attention is given to assessing different types of lamps, dosimetry, published guidelines, and the utilization of targeted phototherapy modalities. Additionally, the integration of phototherapy with other treatment modalities, including its use as a depigmenting therapy in generalized/universal vitiligo, is discussed. Screening for anti-nuclear antibodies and tailoring approaches for non-photo-adapters are also examined. CONCLUSION: In conclusion, this review provides a comprehensive overview of phototherapy for vitiligo treatment. It underscores the evolving landscape of phototherapy and offers insights into optimizing therapeutic outcomes and addressing the challenges ahead. By integrating clinical evidence with molecular understanding, phototherapy emerges as a valuable therapeutic option for managing vitiligo, with potential for further advancements in the field.

Melanin Inhibitory Effect of Tuber himalayense Isolated in Incheon, Korea.

There has been a growing interest in skin beauty and antimelanogenic products. Melanogenesis is the process of melanin synthesis whereby melanocytes are activated by UV light or hormone stimulation to produce melanin. Melanogenesis is mediated by several enzymes, such as tyrosinase (TYR), microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1), and TRP-2. In this study, we investigated the effect of Tuber himalayense extract on melanin synthesis in α-melanocyte-stimulating hormone (α-MSH)-treated B16F10 melanoma cells. We confirmed that T. himalayense extract was not toxic to α-MSH-treated B16F10 melanoma cells and exhibited a significant inhibitory effect on melanin synthesis at concentrations of 25, 50, and 100 µg/ml. Additionally, the T. himalayense extract inhibited melanin, TRP-1, TRP-2, tyrosinase, and MITF, which are enzymes involved in melanin synthesis, in a concentration-dependent manner. Furthermore, T. himalayense extract inhibited the mitogen-activated protein kinase (MAPK) pathways, such as extracellular signal-regulated kinase-1/2 (ERK), c-Jun N-terminal kinase (JNK), and p38. Therefore, we hypothesized that various components of T. himalayense extract affect multiple factors involved in melanogenesis in B16F10 cells. Our results indicate that T. himalayense extract could potentially be used as a new material for preparing whitening cosmetics.

Sexual dimorphism in melanocyte stem cell behavior reveals combinational therapeutic strategies for cutaneous repigmentation.

Vitiligo is an autoimmune skin disease caused by cutaneous melanocyte loss. Although phototherapy and T cell suppression therapy have been widely used to induce epidermal re-pigmentation, full pigmentation recovery is rarely achieved due to our poor understanding of the cellular and molecular mechanisms governing this process. Here, we identify unique melanocyte stem cell (McSC) epidermal migration rates between male and female mice, which is due to sexually dimorphic cutaneous inflammatory responses generated by ultra-violet B exposure. Using genetically engineered mouse models, and unbiased bulk and single-cell mRNA sequencing approaches, we determine that manipulating the inflammatory response through cyclooxygenase and its downstream prostaglandin product regulates McSC proliferation and epidermal migration in response to UVB exposure. Furthermore, we demonstrate that a combinational therapy that manipulates both macrophages and T cells (or innate and adaptive immunity) significantly promotes epidermal melanocyte re-population. With these findings, we propose a novel therapeutic strategy for repigmentation in patients with depigmentation conditions such as vitiligo.

The story of melanocyte: a long way from bench to bedside.

Skin is composed of major layers, namely a superficial epidermis and a deeper dermis. The color of skin is influenced by a number of pigments, including melanin, which is produced by cells called melanocytes. Most skin disorders are relatively benign, but a few, including melanomas, can be fatal. A number of more noticeable disorders, namely albinism and vitiligo, affect the appearance of the skin and its accessory organs. Vitiligo is associated with significant psycho-social morbidity and a major effect on quality of life. Topical steroids, calcineurin inhibitors, phototherapy and surgery are the most common treatments for melanoma. However, there are many patients who do not respond to any of these modalities. The transplantation of cultured or non-cultured melanocyte is the most important treatment for hypopigmentory disorders. This study aims at reviewing the history of melanocyte cultivation, and evaluating the effectiveness of transplantation of cultured cells. For this purpose, the authors examined the initial process of isolation, characterization, and transplantation of epidermal cells. This review, thus, summarizes the current understanding of the cutaneous pigmentary system from the start of synthesis in the pigment cells, along with the response of repigmentation. During the production of melanin, melanosomes are transferred to neighboring keratinocyte in order to form perinuclear melanin caps. The objective of this review is to analyze the melanocytes transplantation in the last century to date, and explore the methods epidermal cells can increase pigmentation in hypo-pigmented areas in skin disorders. Moreover, the focus is on the story of the melanocyte back to 1950s. In addition, prior systemic therapy was associated with a significant increase, based on combined additional therapy, achieving desired results and improved outcomes. Despite the short study of a long way of melanocyte assessment and following up patient treatment, results of the all reports confirmed the efficacy of the method used in the treatment of stable vitiligo patients, who did not respond to the common algorithms of non-invasive treatments.

Tribuloside acts on the PDE/cAMP/PKA pathway to enhance melanogenesis, melanocyte dendricity and melanosome transport.

ETHNOPHARMACOLOGICAL RELEVANCE: Tribuloside, a natural flavonoid extracted from Chinese medicine Tribulus terrestris L., has shown potent efficacy in treating various diseases. In China, the fruits of Tribulus terrestris L. have long been utilized for relieving headache, dizziness, itchiness, and vitiligo. Water-based extract derived from Tribulus terrestris L. can enhance melanogenesis in mouse hair follicle melanocytes by elevating the expression of α-melanocyte stimulating hormone (α-MSH) and melanocortin-1 recepter (MC-1R). Nevertheless, there is a lack of information regarding the impact of tribuloside on pigmentation in both laboratory settings and living organisms. AIM OF THE STUDY: The present research aimed to examine the impact of tribuloside on pigmentation, and delve into the underlying mechanism. MATERIALS AND METHODS: Following the administration of tribuloside in human epidermal melanocytes (HEMCs), we utilized microplate reader, Masson-Fontana ammoniacal silver stain, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) to measure melanin contents, dendrite lengths, melanosome counts; L-DOPA oxidation assay to indicate tyrosinase activity, Western blotting to evaluate the expression of melanogenic and associated phosphodiesterase (PDE)/cyclic adenosine monophosphate (cAMP)/cyclic-AMP dependent protein kinase A (PKA) pathway proteins. A PDE-Glo assay to verify the inhibitory effect of tribuloside on PDE was also conducted. Additionally, we examined the impact of tribuloside on the pigmentation in both zebrafish model and human skin samples. RESULTS: Tribuloside had a notable impact on the production of melanin in melanocytes, zebrafish, and human skin samples. These functions might be attributed to the inhibitory effect of tribuloside on PDE, which could increase the intracellular level of cAMP to stimulate the phosphorylation of cAMP-response element binding (CREB). Once activated, it induced microphthalmia-associated transcription factor (MITF) expression and increased the expression of tyrosinase, Rab27a and cell division cycle protein 42 (Cdc42), ultimately facilitating melanogenesis, melanocyte dendricity, and melanin transport. CONCLUSION: Tribuloside acts on the PDE/cAMP/PKA pathway to enhance melanogenesis, melanocyte dendricity, and melanosome transport; meanwhile, tribuloside does not have any toxic effects on cells and may be introduced into clinical prescriptions to promote pigmentation.

Safety and Efficacy of Autologous Melanocyte/Keratinocyte Transplantation in Patients with Refractory Stable Vitiligo.

BACKGROUND: Vitiligo is a common depigmentation skin disease associated with significant psychosocial morbidity and profound effect on the quality of life. The treatment of vitiligo is still a major challenge in the field of dermatology. Currently, topical steroids, calcineurin inhibitors, ultraviolet phototherapy, surgery, and cultured and non-cultured epidermal melanocyte transplantation are used for the treatment of vitiligo. However, the effectiveness of these treatment modalities is limited by the lack of response, long-term treatment periods, high cost, and inevitable adverse effects. OBJECTIVES: In this study, we aimed to evaluate the efficacy of intraepidermal injection of autologous non-cultured melanocytes and keratinocytes as an alternative therapy for the refractory and stable (RS) vitiligo. METHODS: The treatment procedure was performed on thirty-nine RS vitiligo patients. The autologous skin grafts obtained from the buttock area and epidermis were separated from dermis using dispase. Single-cell autologous melanocytes and keratinocytes were prepared from the epidermis by trypsin/ethylene diamine tetra acetic acid and injected at the concentration of 100-400 × 103 cells/cm2, intra-epidermally to the selected vitiligo lesions. Vitiligo re-pigmentation was monitored employing photography. Photographs were taken prior to and 2, 4, and 6 months after the cell transplantation. Improvement of the skin depigmentation was classified as follows: <25% as minimal response, 26-50% as moderate response, 51-75% as good response, and finally 76-100% as excellent response. RESULTS: Cell infusion appeared to be safe as none of the patients exhibited any adverse effects. At the end of the sixth month follow-up period, of the treated patients, 12.8% demonstrated an excellent response, 36% exhibited a good response, and 51.2% showed a moderate to minimal response to the administered therapy. Obtained significant p value for Wilcoxon test over the checkpoints at 2nd, 4th, and 6th month (p = 0.03, 0.04, and 0.039, respectively) post-cell transplantation confirmed notable growing trend in the re-pigmentation. CONCLUSION: Our findings provide a strong support for the therapeutic efficacy of autologous non-cultured melanocytes and keratinocytes in patients with RS vitiligo.

Hydrolyzed Conchiolin Protein (HCP) Extracted from Pearls Antagonizes both ET-1 and α-MSH for Skin Whitening.

Pearl powder is a famous traditional Chinese medicine that has a long history in treating palpitations, insomnia, convulsions, epilepsy, ulcers, and skin lightining. Recently, several studies have demonstrated the effects of pearl extracts on protection of ultraviolet A (UVA) induced irritation on human skin fibroblasts and inhibition of melanin genesis on B16F10 mouse melanoma cells. To further explore the effect we focused on the whitening efficacy of pearl hydrolyzed conchiolin protein (HCP) on human melanoma MNT-1 cells under the irritation of alpha-melanocyte-stimulating hormone (α-MSH) or endothelin 1 (ET-1) to evaluate the intracellular tyrosinase and melanin contents, as well as the expression levels of tyrosinase (TYR), tyrosinase related protein 1 (TRP-1), and dopachrome tautomerase (DCT) genes and related proteins. We found that HCP could decrease the intracellular melanin content by reducing the activity of intracellular tyrosinase and inhibiting the expression of TYR, TRP-1, DCT genes and proteins. At the same time, the effect of HCP on melanosome transfer effect was also investigated in the co-culture system of immortalized human keratinocyte HaCaT cells with MNT-1. The result indicated that HCP could promote the transfer of melanosomes in MNT-1 melanocytes to HaCaT cells, which might accelerate the skin whitening process by quickly transferring and metabolizing melanosomes during keratinocyte differentiation. Further study is needed to explore the mechanism of melanosome transfer with depigmentation.

[Vitiligo, no longer a fatality in 2023].

Vitiligo is an acquired auto-inflammatory disorder characterized by a depigmentation. It is a polygenic disease developed in a context of allelic variations. Its pathophysiology is complex, associating intrinsic skin defects, exposome triggering factors and innate then adaptive auto-immune activation leading to the loss of melanocytes. The diagnosis is clinical. Nevertheless, Wood's lamp is mandatory to assess the lesions and their activity, especially in fair-skinned patients. The management of vitiligo is long and aims to halt the depigmentation process and to repigment the affected areas. This requires a combination of immunosuppressive topical or systemic treatment with ultraviolet rays from phototherapy or sun exposure.

Le vitiligo est une dépigmentation acquise bien limitée, d'origine auto-immune. Il s'agit d'une maladie polygénique survenant dans un contexte de variations alléliques prédisposant son apparition. Sa physiopathologie est complexe et associe des défauts intrinsèques de la peau, des facteurs déclenchants liés à l'exposome et une activation immunitaire innée, puis adaptative, conduisant à la perte des mélanocytes. Son diagnostic est clinique mais la lumière de Wood est indispensable pour apprécier les lésions et leur activité, notamment sur peau claire. La prise en charge du vitiligo est longue et a pour but d'interrompre la dépigmentation et de repigmenter les zones lésionnelles. Pour cela, il faut associer un traitement immunosuppresseur topique ou systémique à des rayons ultraviolets, soit naturels, soit de la photothérapie.

Acceleration of melanocyte senescence by the proinflammatory cytokines IFNγ and TNFα impairs the repigmentation response of vitiligo patients to narrowband ultraviolet B (NBUVB) phototherapy.

Vitiligo is a chronic autoimmune disease characterized by the T helper 1 (Th1) cytokine-driven immune destruction of melanocytes (MCs). Although narrowband ultraviolet B (NBUVB) phototherapy has been proven to be an effective therapeutic option, the repigmentation response to that phototherapy varies greatly in different vitiligo patients. Here, we demonstrate that there is an increase of NBUVB-induced cellular senescence in vitiligo MCs exposed to Th1 cytokine interferon γ (IFNγ) and/or tumor necrosis factor α (TNFα) in lesional vitiligo skin from poor responders who had undergone NBUVB phototherapy. Supplementation with exogenous recombinant human stem cell factor (rhSCF) in the culture medium as well as the lentiviral vector-mediated overexpression of cKIT could prevent the MCs from the IFNγ/TNFα-accelerated cellular senescence. Mechanistic studies indicated that the reduced ratio of membrane-bound KIT (mKIT) to the soluble form of KIT (sKIT) is directly related to the cellular senescence of vitiligo MCs following exposure to IFNγ and TNFα. Furthermore, the matrix metalloprotease 9 (MMP9) inhibitor GM6001 attenuates the production of sKIT via the suppression of cKIT ectodomain shedding. Altogether, our study indicates that the presence of Th1 cytokines IFNγ and/or TNFα in the epidermal milieu might impair the repigmentation response of vitiligo patients to NBUVB phototherapy.

Mechanism and inhibitory effects of cactus (Opuntia dillenii) extract on melanocytes and its potential application for whitening cosmetics.

Penghu cactus (Opuntia dillenii [Ker.] Haw) is a cactus plant that commonly grows in Penghu Island, Taiwan, Republic of China (ROC). However, still lack of scientific study on the Opuntia dillenii [Ker.] Haw extract on skin-whitening-associated tyrosinase activity and melanin production. The activities of its extract in melanogenesis were investigated in this article. In this experiment, we used an extract from the Penghu cactus (Opuntia dillenii [Ker.] Haw) to study its tyrosinase inhibition, anti-melanin generation, UV-protection effects and wound healing capacity in B16-F10 melanocytes. Without reducing cell growth greatly or causing cell death, 20 g/L cactus extract effectively inhibited the melanin production of B16-F10 cells, and melanogenesis was induced by 3-isobutyl-1-methylxanthine. The cactus extract could also promote cell proliferation. Cactus extract treatment decreased the mRNA expression of insulin-like growth factor 1 (IGF-1) and vascular endothelial growth factor (VEGF) and increased that of transforming growth factor ß (TGF-ß). Thus, it could reduce cell melanin production and promote cell growth but by also reducing IGF-1 and VEGF mRNA expression, may reduce wound scarring and prevent tumor proliferation and swelling. Increasing TGF-ß mRNA expression can help increase collagen to remove wrinkles and help in wound healing. Skin patch test results agreed with in vitro results with B16-F10 melanoma cells. The cactus extract significantly inhibited tyrosinase activity and reduced melanin production, showing a whitening effect on skin tests. Cactus may be a good natural candidate for inhibiting melanin production and promoting cell proliferation.

Vitiligo: An immune disease and its emerging mesenchymal stem cell therapy paradigm.

Melanocyte damage, innate immune response, adaptive immune response, and immune inflammatory microenvironment disorders are involved in the development of the immunological pathogenic mechanism of vitiligo. Mesenchymal stem cells are considered an ideal type of cells for the treatment of vitiligo owing to their low immunogenicity, lower rates of transplant rejection, and ability to secrete numerous growth factors, exosomes, and cytokines in vivo. The regulation of signaling pathways related to oxidative stress and immune imbalance in the immunological pathogenesis of vitiligo can improve the immune microenvironment of tissue injury sites. In addition, co-transplantation with melanocytes can reverse the progression of vitiligo. Therefore, continuous in-depth research on the immunopathogenic mechanism involved in this disease and mesenchymal stem cell-based therapy is warranted for the treatment of vitiligo in the future.

Management of the refractory vitiligo patient: current therapeutic strategies and future options.

Vitiligo is an autoimmune disease that leads to disfiguring depigmented lesions of skin and mucosa. Although effective treatments are available for vitiligo, there are still some patients with poor responses to conventional treatment. Refractory vitiligo lesions are mostly located on exposed sites such as acral sites and lips, leading to significant life stress. Understanding the causes of refractory vitiligo and developing targeted treatments are essential to enhance vitiligo outcomes. In this review, we summarized recent treatment approaches and some potential methods for refractory vitiligo. Janus kinase inhibitors have shown efficacy in refractory vitiligo. A variety of surgical interventions and fractional carbon dioxide laser have been widely applied to combination therapies. Furthermore, melanocyte regeneration and activation therapies are potentially effective strategies. Patients with refractory vitiligo should be referred to psychological monitoring and interventions to reduce the potential pathogenic effects of chronic stress. Finally, methods for depigmentation and camouflage may be beneficial in achieving uniform skin color and improved quality of life. Our ultimate focus is to provide alternative options for refractory vitiligo and to bring inspiration to future research.

Reduced Elastin Fibers and Melanocyte Loss in Vitiliginous Skin Are Restored after Repigmentation by Phototherapy and/or Autologous Minigraft Transplantation.

Vitiligo is a hypopigmentation disease characterized by melanocyte death in the human epidermis. However, the mechanism of vitiligo development and repigmentation is largely unknown. Dermal fiber components might play an important role in vitiligo development and repigmentation. Indeed, our preliminary study demonstrated that elastin fibers were decreased in vitiliginous skin, suggesting that the elastin fiber is one of the factors involved in vitiligo development and repigmentation. To confirm our hypothesis, we investigated whether elastin fibers can be restored after treatment using phototherapy and/or autologous skin transplantation. Punch biopsies from 14 patients of stable nonsegmental vitiligo vulgaris were collected from nonlesional, lesional, and repigmented skin, and processed to dopa and combined dopa-premelanin reactions. Melanocytes positive to the dopa reaction and melanoblasts/melanocytes positive to the combined dopa-premelanin reaction were surveyed. Moreover, elastin fibers were detected by Victoria blue staining. Numerous melanocytes and melanoblasts were observed in the epidermis of repigmented skin after the treatment. Moreover, in the dermis of repigmented skin, elastin fibers were completely recovered or even upregulated. These results suggest that melanocyte loss in the vitiliginous skin, as well as melanocyte differentiation in repigmented skin, may be at least in part regulated by elastin fibers in the dermis.

Plants as Modulators of Melanogenesis: Role of Extracts, Pure Compounds and Patented Compositions in Therapy of Pigmentation Disorders.

The kingdom of plants as a "green biofabric" of valuable bioactive molecules has long been used in many ailments. Currently, extracts and pure compounds of plant origin are used to aid in pigmentation skin problems by influencing the process of melanogenesis. Melanin is a very important pigment that protects human skin against ultraviolet radiation and oxidative stress. It is produced by a complex process called melanogenesis. However, disturbances in the melanogenesis mechanism may increase or decrease the level of melanin and generate essential skin problems, such as hyperpigmentation and hypopigmentation. Accordingly, inhibitors or activators of pigment formation are desirable for medical and cosmetic industry. Such properties may be exhibited by molecules of plant origin. Therefore, that literature review presents reports on plant extracts, pure compounds and compositions that may modulate melanin production in living organisms. The potential of plants in the therapy of pigmentation disorders has been highlighted.

Molecular Analysis of the Melanogenesis Inhibitory Effect of Saponins-Rich Fraction of Argania spinosa Leaves Extract.

Plant saponins are abundant and diverse natural products with a great potential for use in drug-discovery research. Here, we evaluated extracts of saponins-rich fractions of argan leaves and argan oil extraction byproducts (shell, pulp, press cake) for their effect on melanogenesis. Results show that from among the samples tested, only the saponins-rich fraction from leaves (ALS) inhibited melanin production in B16 murine melanoma (B16) cells. The mechanism of the melanogenesis inhibition was elucidated by determining the protein and mRNA expression of melanogenesis-associated enzymes tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase (DCT), and microphthalmia-associated transcription factor (MITF), and performing DNA microarray analysis. Results showed that 10 µg/mL ALS significantly inhibited melanogenesis in B16 cells and human epidermal melanocytes by 59% and 48%, respectively, without cytotoxicity. The effect of ALS on melanogenesis can be attributed to the decrease in TYR, TRP1, and MITF expression at the protein and mRNA levels. MITF inhibition naturally led to the downregulation of the expression of Tyr and Trp1 genes. Results of the DNA microarray analysis revealed the effect on melanogenesis-associated cAMP and Wnt signaling pathways' genes. The results of this study suggest that ALS may be used in cosmeceuticals preparations for hyperpigmentation treatment.

Mechanisms of ultraviolet-induced melasma formation: A review.

Melasma, a pigmentation disorder, commonly occurs in exposed skin areas and can be attributed to several factors. Ultraviolet radiation (UVR) is the primary factor that induces and aggravates melasma. Considering gene expression, exposed skin areas experience abnormal gene expression, involving melanin metabolism, oxidative stress, impaired skin barrier function, and abnormal composition of nerve factors. From a histological perspective, UVR can cause basement membrane collapse, melanocyte sinking, and disorders of skin lipid metabolism. Emerging therapies have focused on these pathological alterations in melasma, including platelet-rich plasma, mesotherapy, and phytochemicals. Understanding the role of UVR in the development of melasma can facilitate early prevention and highlight the future direction of melasma treatment.

Anti-Melanogenesis Activity of Crocodile (Crocodylus siamensis) White Blood Cell Extract on Ultraviolet B-Irradiated Melanocytes.

Ultraviolet (UV) radiation generates a range of biological effects in the skin, which includes premature skin aging, hyperpigmentation, and cancer. Therefore, the development of new effective agents for UV-related skin damage remains a challenge in the pharmaceutical industry. This study aims to test the inhibitory effect of crocodile white blood cell (cWBC) extract, a rich source of bioactive peptides, on ultraviolet B (UVB)-induced melanocyte pigmentation. The results showed that cWBC (6.25-400 µg/mL) could inhibit tyrosinase without adduct formation by 12.97 ± 4.20% on average. cWBC pretreatment (25-100 µg/mL) had no cytotoxicity and reduced intracellular melanin to 111.17 ± 5.20% compared with 124.87 ± 7.43 for UVB condition. The protective role of cWBC pretreatment against UVB was exhibited by the promotion of cell proliferation and the prevention of UVB-induced morphological change as observed from F actin staining. The decrease of microphthalmia-associated transcription factor expression levels after cWBC pretreatment might be a mechanism by which cWBC suppresses UVB-induced pigmentation. These results suggest that cWBC could be beneficial for the prevention of UVB-induced skin pigmentation.

Anti-melanogenic effects of glucosylceramides and elasticamide derived from rice oil by-products in melanoma cells, melanocytes, and human skin.

Glucosylceramides (GlcCer), which are present in many edible plants, suppress melanin production in mouse melanocytes. Rice GlcCer consist of multiple molecules that comprise different types of sphingoid bases as well as diverse lengths and stereotypes of free fatty acids. Adjacent to the GlcCer fraction, there are free ceramides (Cer) as minor constituents. However, the anti-melanogenic activities of individual GlcCer and Cer remain unknown. Therefore, we herein isolated 13 GlcCer and elasticamide, a Cer [AP] from the gummy by-products of rice bran oil, and examined their anti-melanogenic activities. In theophylline-induced melanogenesis in B16 melanoma cells, GlcCer [d18:2(4E,8Z)/18:0], GlcCer [d18:2(4E,8Z)/20:0], and elasticamide significantly suppressed melanin production with IC50 values of 6.6, 5.2, and 3.9 µM, respectively. Elasticamide, but not GlcCer [d18:2 (4E,8Z)/20:0], suppressed melanogenesis in human 3D-cultured melanocytes and the expression of tyrosinase-related protein 1 in normal human melanocytes. Based on these results, we conducted a clinical trial on the effects of rice ceramide extract (Oryza ceramide®), containing 1.2 mg/day of GlcCer and 56 µg/day of elasticamide, on UV-B-induced skin pigmentation. The ingestion of Oryza ceramide® for 8 weeks significantly suppressed the accumulation of melanin 7 days after UV irradiation (1288 and 1546 mJ/cm2 ·S). Rice-derived GlcCer and elasticamide, which exhibited anti-melanogenic activities, were suggested to contribute to the suppressive effects of Oryza ceramide® on UV-induced skin pigmentation. Although the mechanisms underlying the anti-melanogenic activities of GlcCer remain unclear, elasticamide was identified as a promising Cer that exhibits anti-melanogenic activity. PRACTICAL APPLICATIONS: The anti-melanogenic activities of rice-derived GlcCer and elasticamide currently remain unclear. We herein demonstrated the inhibitory effects of individual GlcCer and elasticamide on melanogenesis in melanoma cells, melanocytes, and human skin.

The Modulation of Melanogenesis in B16 Cells Upon Treatment with Plant Extracts and Isolated Plant Compounds.

Plants are a rich source of secondary metabolites that exhibit numerous desired properties. The compounds may influence the biology of melanocytes, pigment cells that produce melanin, by modulating numerous signaling pathways, including cAMP/PKA, MAPKs and PI3K/AKT. Its downstream target is microphthalmia-associated transcription factor, responsible for the expression of the tyrosinase enzyme, which plays a major role in melanogenesis. Therefore, this literature review aims to provide insights related to melanogenesis modulation mechanisms of plant extracts and isolated plant compounds in B16 cells. Database searches were conducted using online-based library search instruments from 2012 to 2022, such as NCBI-PubMed and Google Scholar. Upregulation or downregulation of signaling pathways by phytochemicals can influence skin hypo- and hyperpigmentation by changing the level of melanin production, which may pose a significant cosmetic issue. Therefore, plant extracts or isolated plant compounds may be used in the therapy of pigmentation disorders.

Lycium barbarum polysaccharide promotes proliferation of human melanocytes via activating the Nrf2/p62 signaling pathway by inducing autophagy in vitro.

Vitiligo is a skin disease characterized by lack of functional melanocytes. Lycium barbarum polysaccharide (LBP) has been demonstrated to preserve keratinocytes and fibroblasts against oxidative stress. This study aimed to explore the efficacy and underlying mechanisms of LBP on autophagy in H2 O2 -damaged human melanocytes. Cellular viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and annexin V-fluorescein isothiocyanate/propidium iodide double staining. Reverse transcription-polymerase chain reaction, western blotting and electron microscopy were performed to detect autophagy. The protein expression level of Nrf2 and p62 were assessed by western blotting. Plasmid transfection and lentiviral infection were used to overexpress and silence Nrf2 in PIG1 cells. LBP promoted the proliferation and inhibited apoptosis of H2 O2 -damaged PIG1 cells. LBP increased the proliferation of H2 O2 -damaged PIG1 cells via induction of autophagy, and Nrf2 shRNA experiment confirmed that LBP activated the Nrf2/p62 signal pathway. These results suggest that LBP may be used for the treatment of vitiligo. PRACTICAL APPLICATIONS: Goji berry is the mature and dried fruit of Lycium barbarum L., which is a common food with a long history in China, as well as a Traditional Chinese Medicine. Our previous research found that LBP could activated the Nrf2/ARE pathway in an ultraviolet (UV)-induced photodamage model of keratinocytes, and increase the levels of phase II detoxification and antioxidant enzymes. We firstly confirmed the anti-vitiligo effects of L. barbarum polysaccharide (LBP) by inducing autophagy and promoted proliferation of human melanocytes, and LBP induced autophagy via activating the Nrf2/p62 signaling pathway in this study. These results proved that LBP can be an effective therapy for vitiligo treatment.