ABSTRACT
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.
Subject(s)
Melanoma , Oryza , Alkanes , Amides , Animals , Ceramides/metabolism , Ceramides/pharmacology , Fatty Acids, Nonesterified/metabolism , Fatty Acids, Nonesterified/pharmacology , Glucosylceramides/pharmacology , Humans , Melanins , Melanocytes/metabolism , Melanocytes/radiation effects , Melanoma/drug therapy , Mice , Monophenol Monooxygenase/metabolism , Plant Extracts/pharmacology , Rice Bran Oil/metabolism , Rice Bran Oil/pharmacology , Theophylline/metabolism , Theophylline/pharmacologyABSTRACT
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.
Subject(s)
Alligators and Crocodiles , Alligators and Crocodiles/metabolism , Animals , Leukocytes , Melanins/metabolism , Melanocytes/metabolism , Melanocytes/radiation effects , Monophenol Monooxygenase/metabolism , Ultraviolet Rays/adverse effectsABSTRACT
In the last few years, the focus of phototherapy has shifted toward the visible (400-700 nm) part of the electromagnetic spectrum of light. Lately, it has been demonstrated that visible light (VL) can have both beneficial and detrimental effects, especially on the skin. Previously and until now, the most harmful effects on the skin are associated with ultraviolet radiation (UVR). After exposure to natural light, the most evident and immediate change is observed on skin pigmentation. Various wavelengths within the visible spectrum have been reported to alter skin pigmentation. However, the underlying mechanisms are incompletely understood so far. The article aims to shed light on the progress made in the photobiology field (photobiomodulation, PBM) to study the role of visible light on skin melanocytes.
Subject(s)
Melanocytes , Skin Pigmentation , Skin , Ultraviolet Rays , Melanocytes/radiation effects , Photobiology , Skin/radiation effects , Ultraviolet Rays/adverse effectsABSTRACT
Phototherapy is an effective therapeutic option in the treatment of vitiligo; however, responses varied among the different types. The underlying mechanism has scarcely been investigated. To investigate and compare the effects of phototherapy on the mutation of melanocyte lineage differentiated from human scalp-derived neural crest stem cells (HS-NCSCs) with p75 neurotrophin receptor expression positive and p75 neurotrophin receptor expression negative group in vitro, the HS-NCSCs were isolated from fetal scalp tissue, which is identified by immunofluorescent staining. The p75(+) and p75(-) cells from HS-NCSCs were isolated by magnetic cell sorting, respectively. The embryonic neural crest stem cell biomarkers were detected by RT-PCR. Narrow-band UVB (NB-UVB) was used to irradiate the cells. Cell proliferation was evaluated by cell count. Tyrosinase, Tyrp1, and Tyrp2 gene expression were measured by quantitative RT-PCR. Tyrosinase and GRCR protein levels were investigated by Western blot analysis. The electrophoretic strip showed that Sox2, Oct4, Sox10, and Nestin of p75(+) HS-NCSCs were brighter than the p75(-) HS-NCSCs. After the same dose radiation with NB-UVB, the cell proliferation of p75(+) group showed less inhibitory rate compared with the p75(-) HS-NCSCs. The tyrosinase mRNA and protein expression of differentiated melanocytes increased significantly in the group of p75(+) HS-NCSCs compared with the p75(-) group. The melanocytic mutation of p75(+) HS-NCSCs increased significantly compared with the p75(-) HS-NCSCs under NB-UVB, which indicated there were more melanocyte precursors in the differentiated cells from p75(+) HS-NCSCs. This may provide new insights for the different repigmentation efficacy of segmental and non-segmental vitiligo.
Subject(s)
Cell Lineage/radiation effects , Melanocytes/cytology , Melanocytes/radiation effects , Neural Crest/cytology , Phototherapy , Receptor, Nerve Growth Factor/metabolism , Scalp/cytology , Stem Cells/cytology , Biomarkers/metabolism , Cell Differentiation/radiation effects , Cell Proliferation/radiation effects , Humans , Melanocytes/metabolism , Mutation/genetics , Stem Cells/radiation effects , Ultraviolet TherapySubject(s)
Critical Pathways , Immunologic Factors/administration & dosage , Skin Pigmentation/radiation effects , Ultraviolet Therapy/methods , Vitiligo/therapy , Administration, Cutaneous , Administration, Oral , Combined Modality Therapy/methods , Humans , Melanocytes/drug effects , Melanocytes/immunology , Melanocytes/radiation effects , Skin/cytology , Skin/drug effects , Skin/radiation effects , Skin Pigmentation/drug effects , Skin Pigmentation/immunology , Treatment Outcome , Vitiligo/immunologySubject(s)
Hyperpigmentation/prevention & control , Semiconductors , Ultraviolet Therapy/instrumentation , Cell Line , Cell Proliferation/radiation effects , Fibroblasts/radiation effects , Humans , Hyperpigmentation/etiology , Melanocytes/radiation effects , Skin Pigmentation/radiation effects , Ultraviolet Therapy/adverse effectsABSTRACT
Vitiligo is a common depigment of skin disorder due to loss of functional melanocytes. Recently, the phototherapy with a 308-nm xenon-chloride excimer laser (UVB laser) is wildly used in vitiligo treatment. However, excessive UVB will induce photo-damage and photo-carcinogenesis in melanocytes. Previous studies revealed a protective effect of heat on UVB-induced melanocyte damage. In this study, we combined heat stress pretreatment with UVB to evaluate whether heat stress pretreatment has an ameliorative effect on UVB-induced damage. Human primary melanocytes (HMCs) were cultured and irradiated with a 308-nm laser with/without heat treatment. MTT assay, apoptosis analysis, and comet assay were conducted to monitor the damage of HMCs. Western blot and immunofluorescence staining were performed to assess the expression and subcellular localization of HSP70. HMCs heated at 42 °C for 1 h exhibit no cytotoxicity. Furthermore, preheat treatment attenuated the UVB laser-induced injury, reduced the DNA damage, and attenuated the cell apoptosis. The level and the localization of HSP70 determined the protective effects against UVB-induced DNA damage. Combining preheat treatment with a 308-nm xenon-chloride excimer laser would be a potential therapeutic method not only promotes the repigment of vitiligo but also reduces the UVB-induced photo-damage.
Subject(s)
DNA Damage , Heat-Shock Response/genetics , Heat-Shock Response/radiation effects , Lasers/adverse effects , Melanocytes/metabolism , Melanocytes/radiation effects , Apoptosis/genetics , Apoptosis/radiation effects , HSP70 Heat-Shock Proteins/metabolism , Humans , Ultraviolet Rays/adverse effectsABSTRACT
Clinical studies have proven that ultraviolet B (UVB) based phototherapy can induce perifollicular and marginal repigmentation patterns in the skin of vitiligo patients. It is, however, difficult to conceive how melanocytes can easily exit from their tightly interconnected epidermal microenvironment to reenter a different location in the skin to establish a new network with neighboring keratinocytes. While it is known that matrix metalloprotease 9 (MMP9) is involved in the degradation of the extracellular matrix in physiological or pathological processes, little is known about whether MMP9 affects melanocyte migration in vitiligo repigmentation. To investigate the effects of the p53 transient receptor potential cation channel subfamily M member 1 (TRPM1)/microRNA (miR/miRNA)211MMP9 axis to regulate melanocyte migration following exposure to UVB, the expression profile of MMP9 in cultured human melanocytes transfected with or without the miR211mimic and p53GFP lentiviral vector, respectively were determined. Quantitative polymerase chain reaction and western blotting were used to examine p53, TRPM1 and MMP9 mRNA and protein levels in UVBexposed and unexposed cells. The capacity of melanocytes to migrate on collagen IV substrate was estimated using a Transwell migration assay. Interestingly, the upregulation of p53 and MMP9 at the mRNA and protein levels was evident in melanocytes treated with single or repeat exposures to UVB, whereas levels of TRPM1 and miR211 were significantly suppressed in UVBexposed melanocytes compared with the UVBunexposed control cells. These results indicate that the p53TRPM1/miR211MMP9 axis is significantly activated in melanocytes exposed to UVB. Notably, the ability of melanocyte migration was altered by the overexpression of p53 using a lentiviral vector and by the upregulation of miR211 using an miRNA mimic. That altered migration could be neutralized by cotreatment with GM6001 (a broadspectrum MMP inhibitor). Overall, these results show that the MMP9mediated migration of melanocytes is regulated by a novel mechanism driven by the p53TRPM1/miR211MMP9 axis. Activation of the p53TRPM1/miR211MMP9 axis potentially represents an attractive therapeutic target to improve repigmentation outcomes in vitiligo patients.
Subject(s)
Matrix Metalloproteinase 9/metabolism , Melanocytes/metabolism , Melanocytes/radiation effects , MicroRNAs/metabolism , TRPM Cation Channels/metabolism , Tumor Suppressor Protein p53/metabolism , Ultraviolet Rays , Adolescent , Adult , Blotting, Western , Cell Movement/radiation effects , Cells, Cultured , Humans , Young AdultABSTRACT
BACKGROUND: In-vitro studies showed that Leucine-rich glioma inactivated 3 (LGI3) is a keratinocyte-derived cytokine that stimulates melanin synthesis and is increased after ultra violet B (UVB) irradiation. So, we postulated that LGI3 may be involved in vitiligo aetiopathogenesis and may participate in narrow band ultra violet B (NB-UVB) induced pigmentation in vitiligo. OBJECTIVES: To assess this hypothesis, lesional LGI3 immunohistochemical expression of vitiligo patients before and after NB-UVB phototherapy was studied, and its correlation with repigmentation was evaluated. METHODS: Forty vitiligo patients and 20 age, sex, and skin phenotype-matched controls were enrolled. Patients were treated with NB-UVB thrice weekly for 12 weeks. VASI score was evaluated before and after NB-UVB sessions. For vitiligo patients, baseline LGI3 immunohistochemical staining was estimated, and compared to that of controls and to its post-treatment data in those patients. Results: Baseline LGI3 immunohistochemical studied parameters (expression, intensity, percentage and H score) were significantly lower in vitiligo cases than controls (p=0.003, 0.013, 0.001 and 0.001 respectively). After 12 weeks of NB-UVB phototherapy, these LGI3 immunohistochemical parameters were up-regulated and became comparable to that of controls (p >0.05 for all). There was a significant positive correlation between the improvement of both VASI score and LGI3 H score mean values (r=-0.349 , p=0.027). STUDY LIMITATIONS: Small number of investigated subjects. CONCLUSIONS: Decreased LGI3 protein may play an active role in vitiligo pathogenesis and its up-regulation after NB-UVB phototherapy, may actively participate in NB-UVB photo-induced melanogenesis.
Subject(s)
Cytokines/analysis , Proteins/analysis , Ultraviolet Therapy/methods , Vitiligo/pathology , Vitiligo/radiotherapy , Adolescent , Adult , Case-Control Studies , Child , Female , Humans , Immunohistochemistry , Keratinocytes/radiation effects , Male , Melanocytes/radiation effects , Middle Aged , Nerve Tissue Proteins , Reference Values , Severity of Illness Index , Statistics, Nonparametric , Time Factors , Treatment Outcome , Young AdultABSTRACT
Abstract: Background: In-vitro studies showed that Leucine-rich glioma inactivated 3 (LGI3) is a keratinocyte-derived cytokine that stimulates melanin synthesis and is increased after ultra violet B (UVB) irradiation. So, we postulated that LGI3 may be involved in vitiligo aetiopathogenesis and may participate in narrow band ultra violet B (NB-UVB) induced pigmentation in vitiligo. Objectives: To assess this hypothesis, lesional LGI3 immunohistochemical expression of vitiligo patients before and after NB-UVB phototherapy was studied, and its correlation with repigmentation was evaluated. Methods: Forty vitiligo patients and 20 age, sex, and skin phenotype-matched controls were enrolled. Patients were treated with NB-UVB thrice weekly for 12 weeks. VASI score was evaluated before and after NB-UVB sessions. For vitiligo patients, baseline LGI3 immunohistochemical staining was estimated, and compared to that of controls and to its post-treatment data in those patients. Results: Baseline LGI3 immunohistochemical studied parameters (expression, intensity, percentage and H score) were significantly lower in vitiligo cases than controls (p=0.003, 0.013, 0.001 and 0.001 respectively). After 12 weeks of NB-UVB phototherapy, these LGI3 immunohistochemical parameters were up-regulated and became comparable to that of controls (p >0.05 for all). There was a significant positive correlation between the improvement of both VASI score and LGI3 H score mean values (r=-0.349 , p=0.027). Study limitations: Small number of investigated subjects. Conclusions: Decreased LGI3 protein may play an active role in vitiligo pathogenesis and its up-regulation after NB-UVB phototherapy, may actively participate in NB-UVB photo-induced melanogenesis.
Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Middle Aged , Young Adult , Ultraviolet Therapy/methods , Vitiligo/pathology , Vitiligo/radiotherapy , Proteins/analysis , Cytokines/analysis , Reference Values , Time Factors , Severity of Illness Index , Immunohistochemistry , Case-Control Studies , Keratinocytes/radiation effects , Treatment Outcome , Statistics, Nonparametric , Melanocytes/radiation effectsABSTRACT
BACKGROUND: The induction of skin pigmentation by ultraviolet (UV) radiation has been shown to result from factors secreted from UV-exposed keratinocytes that enhance melanogenesis in melanosomes (MSs) and stimulates their transfer to keratinocytes. Among those factors, it has been reported that α-melanocyte stimulating hormone, which is converted from the precursor proopiomelanocortin (POMC) following UV exposure, stimulates the transfer of MSs from melanocytes to surrounding keratinocytes. OBJECTIVE: The purpose of this study was to evaluate the effects of a red pumpkin seed (RPS) extract on the transfer of MSs to keratinocytes and to clarify the involvement of reactive oxygen species (ROS) on the UVB-induced transfer of MSs. METHODS: The transfer of MSs into keratinocytes was examined by measuring the incorporation of fluorescent beads, which were used as pseudo-MSs. mRNA expression levels of POMC, Nrf2, and Nrf2-related genes were determined using real-time PCR. Intracellular ROS levels were estimated with H2 DCFDA. RESULTS: The incorporation of fluorescent beads into keratinocytes was enhanced by treatment with the conditioned medium (CM) from keratinocytes exposed to UVB or H2 O2 . UVB or H2 O2 exposed keratinocytes had an up-regulated mRNA expression level of POMC. Treatment of keratinocytes with the RPS extract enhanced their intracellular antioxidant system via the activation of Nrf2 signaling and suppressed their incorporation of fluorescent beads that had been stimulated by the CM from UVB or H2 O2 exposed keratinocytes. CONCLUSION: These results indicate that the RPS extract suppresses MS transfer stimulated by ROS generated following UVB exposure through the activation of Nrf2 signaling.
Subject(s)
Cucurbita/chemistry , Melanosomes/metabolism , NF-E2-Related Factor 2/metabolism , Plant Extracts/pharmacology , Skin Pigmentation/drug effects , Cell Line , Humans , Keratinocytes/drug effects , Keratinocytes/metabolism , Keratinocytes/radiation effects , Melanocytes/drug effects , Melanocytes/metabolism , Melanocytes/radiation effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Signal Transduction/radiation effects , Skin Pigmentation/radiation effects , Ultraviolet Rays/adverse effectsABSTRACT
Oxidative stress is an integral element that influences a variety of biochemical reactions throughout the body and is known to play a notable role in melanogenesis. Exogenous triggers of oxidative stress, such as ultraviolet radiation (UVR) and visible light (VL), lead to pigment formation through somewhat different pathways, but both share a common endpoint-the potential to generate cosmetically undesirable hyperpigmentation. Though organic and inorganic sunscreens are available to protect against the UVR portion of the electromagnetic spectrum, coverage is lacking to protect against the VL spectrum. In this manuscript, we review the phases of tanning, pathways of melanogenesis triggered by UVR and VL, and the associated impact of oxidative stress. We also discuss the known intrinsic mechanisms and paracrine regulation of melanocytes that influence their response to UVR. Understanding these mechanisms and their role in UVR-induced hyperpigmentation should potentially lead to identification of useful targets that can be coupled with antioxidant therapy to alleviate this effect.
Subject(s)
Antioxidants/therapeutic use , Hyperpigmentation/drug therapy , Melanins/biosynthesis , Oxidative Stress , Suntan/radiation effects , Ultraviolet Rays/adverse effects , Carotenoids/therapeutic use , Humans , Hyperpigmentation/etiology , Melanocytes/physiology , Melanocytes/radiation effects , Paracrine Communication , Phytotherapy , Plant Extracts/therapeutic use , Polyphenols/therapeutic use , PolypodiumABSTRACT
BACKGROUND: The melanocyte and keratinocyte transplantation procedure (MKTP) is a safe and effective procedure in treatment of vitiligo. Major advantage of this technique is that a small area of donor skin is needed to cover a large recipient area. To date, there is no consensus on the optimal donor-to-recipient ratio (D/R) required to achieve acceptable repigmentation following melanocyte and keratinocyte transplantation procedure (MKTP) in generalized vitiligo. It has been postulated that the addition of post-transplantation phototherapy may enhance the results. This is first study to assess two different (D/R) ratios with or without adjuvant phototherapy. OBJECTIVE: To compare the repigmentation after MKTP using two different D/R ratios (1/3 and 1/10) with and without adjuvant phototherapy (NB-UVB). METHODS AND MATERIALS: In this non randomized prospective clinical trial, 42 patients with stable generalized vitiligo bilateral and symmetrical in distribution were included. Patients were divided into two groups, 21 patients with a total of 50 lesions were treated with MKTP using a D/R ratio of 1/3 (Group I; 3000 ± 500 cell/mm2 ) and the other 21 patients with a total of 52 lesions were treated by MKTP using a D/R ratio of 1/10 (Group II; 1000 ± 200 cell/mm2 ). To study the role of adjuvant phototherapy on repigmentation, lesions in each patient were divided into two subgroups (a and b): lesions in subgroups Ia and IIa (did not receive NB-UVB) and lesions in subgroups Ib and IIb (received adjuvant phototherapy NB-UVB, two sessions per week for 6 months). The overall grading of repigmentation used was excellent (90%-100% repigmentation), good (75%-89%), fair (50%-74%), and poor (<50%). Also, the percentage of VASI change and color matching were used to assess the results. The study design was approved by the ethical committee of the Faculty of Medicine, Assiut University (IRB attached). RESULTS: The mean percentage of repigmentation was significantly better in group I than group II cases in both areas with or without adjuvant NB-UVB. It was 86.00 ± 16.21 and 87.62 ± 11.66 in subgroups Ia and Ib, respectively, vs 24.14 ± 18.08 and 29.98 ± 16.34 in subgroups IIa and IIb, respectively (P value was 0.000). The percent of excellent response was significantly better in group I than group II. It was 60% and 64% in subgroups Ia and Ib, respectively, and 7.6 and 11.5 in subgroups IIa and IIb, respectively (P value was 0.000). The mean percentage of VASI change was significantly better in group I than group II cases in both areas. It was -90.74 ± 15.84 and -92.06 ± 11.86 in subgroups Ia and Ib, respectively, vs -23.10 ± 32.85 and -26.03 ± 35.15 in subgroups IIa and IIb, respectively (P value was 0.000). The percent of excellent color match was better in group I than group II. It was 84% and 88% in subgroups Ia and Ib, respectively, vs 34.6 in both subgroups IIa and IIb (P < 0.05). A higher density of epidermal cells was transplanted in the recipient area in group I (3000 ± 500 cell/mm2 ) compared to group II (1000 ± 200 cell/mm2 ). There were no statistically significant differences between subgroups (Ia vs Ib and IIa vs IIb) although percentage of repigmentation was slightly better in NB-UVB subgroups. CONCLUSIONS: The higher density of epidermal cells used in the suspension, the higher the percentage of repigmentation obtained. The usage of adjuvant phototherapy following NKMT can enhance the repigmentation response.
Subject(s)
Keratinocytes/transplantation , Melanocytes/transplantation , Skin Pigmentation/radiation effects , Ultraviolet Therapy/methods , Vitiligo/therapy , Adolescent , Adult , Combined Modality Therapy/methods , Female , Humans , Keratinocytes/radiation effects , Male , Melanocytes/radiation effects , Prospective Studies , Skin/cytology , Skin/radiation effects , Treatment Outcome , Young AdultABSTRACT
0.5-1% of the world's population is affected by vitiligo, a disease characterized by a gradual depigmentation of the skin. Baicalin and berberine are natural compounds with beneficial activities, such as antioxidant, anti-inflammatory and proliferative effects. These polyphenols could be useful for the treatment of vitiligo symptoms, and their efficacy can be improved by loading in suitable carriers. The aim of this work was to formulate and characterize baicalin or berberine loaded ultradeformable vesicles, and demonstrate their potential as adjuvants in the treatment of vitiligo. The vesicles were produced using a previously reported simple, scalable method. Their morphology, size distribution, surface charge and entrapment efficiency were assessed. The ability of the vesicles to promote the permeation of the polyphenols was evaluated. The antioxidant and photoprotective effects were investigated in vitro using keratinocytes and fibroblasts. Further, the stimulation of melanin production and tyrosinase activity in melanocytes after treatment with the vesicles were assessed. Ultradeformable vesicles were small in size, homogeneously dispersed, and negatively charged. They were able to incorporate high amounts of baicalin and berberine, and promote their skin permeation. In fact, the polyphenols concentration in the epidermis was higher than 10%, which could be indicative of the formation of a depot in the epidermis. The vesicles showed remarkable antioxidant and photoprotective capabilities, presumably correlated with the stimulation of melanin production and tyrosinase activity. In conclusion, baicalin or berberine ultradeformable vesicles, and particularly their combination, may represent promising nanosystem-based adjuvants for the treatment of vitiligo symptoms.
Subject(s)
Antioxidants/pharmacology , Berberine/pharmacology , Flavonoids/pharmacology , Melanins/biosynthesis , Melanocytes/drug effects , Sunscreening Agents/pharmacology , Animals , Antioxidants/metabolism , Berberine/metabolism , Cell Line, Transformed , Drug Compounding/methods , Flavonoids/metabolism , Humans , Keratinocytes/cytology , Keratinocytes/drug effects , Keratinocytes/metabolism , Keratinocytes/radiation effects , Liposomes/chemical synthesis , Melanins/agonists , Melanocytes/cytology , Melanocytes/metabolism , Melanocytes/radiation effects , Monophenol Monooxygenase/metabolism , Permeability , Skin/drug effects , Skin/metabolism , Skin Absorption , Static Electricity , Sunscreening Agents/metabolism , Swine , Ultraviolet Rays , Vitiligo/drug therapyABSTRACT
Melanocytes in hair are located around dermal papilla cells at the tip of the hair follicle. In this study, we examined the melanogenesis of a three-dimensional (3D) hair dermal papilla model treated with natural extracts and electromagnetic fields (EMFs). The 3D model involved dermal papilla-like tissue (DPLT), an aggregation of a mixture of dermal papilla cells, and melanocytes in microwells. Rice bran extract (RBE), an EMF, and RBE/EMF were applied to different DPLT groups. The LDH assay indicated no cell stress in all experimental groups, and detection of tyrosinase activity demonstrated high activity in the RBE/EMF group. Western blot analysis of the RBE, EMF, and RBE/EMF groups revealed increased MITF, TRP-1, and tyrosinase expression. In addition, the mRNA expression of ET-1, laminin, bFGF, ß-catenin, MITF, and tyrosinase was increased in the RBE/EMF group, as demonstrated by RT-qPCR analysis. HMB45 and Fontana-Masson immunostaining showed that the RBE/EMF group had the highest melanin content. Therefore, RBE and EMF may be used as a material and therapy, respectively, for the treatment of vitiligo and white hair, through activation of melanogenesis in melanocytes. Bioelectromagnetics. 39:595-603, 2018. © 2018 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc..
Subject(s)
Dermis/metabolism , Electromagnetic Fields , Melanins/biosynthesis , Melanocytes/metabolism , Oryza/chemistry , Plant Extracts/pharmacology , Cell Differentiation/drug effects , Cell Differentiation/radiation effects , Cyclic AMP Response Element-Binding Protein/metabolism , Dermis/cytology , Dermis/drug effects , Dermis/radiation effects , Gene Expression Regulation/drug effects , Gene Expression Regulation/radiation effects , Humans , L-Lactate Dehydrogenase/metabolism , Melanocytes/cytology , Melanocytes/drug effects , Melanocytes/radiation effects , Monophenol Monooxygenase/metabolism , Phosphoproteins/metabolismSubject(s)
Lasers, Solid-State/therapeutic use , Low-Level Light Therapy , Melanosis/radiotherapy , Asian People , Dendritic Cells/radiation effects , Female , Humans , Lasers, Solid-State/adverse effects , Lasers, Solid-State/classification , Low-Level Light Therapy/adverse effects , Melanins/radiation effects , Melanocytes/radiation effects , Microscopy, Confocal , Pain/etiology , Patient SatisfactionABSTRACT
Leukoderma secondary to Q-switched 1064-nm neodymium-doped yttrium aluminium garnet laser is usually refractory to treatment. The pathogenesis was cumulative phototoxic damage to melanocytes and eventually resulted in melanocytopenia. Wood's light or UV imaging can help observe early leukoderma before it becomes apparent clinically and determine the degree of melanocytopenia before conducting a biopsy. NB-UVB phototherapy and 308-nm excimer laser can potentially worsen the pre-existing melasma lesions and may not be effective if the lesions have already become melanocytopenic. Epidermal grafting can replenish the hypopigmented area with melanocytes without worsening melasma.
Subject(s)
Lasers, Solid-State/adverse effects , Low-Level Light Therapy/adverse effects , Melanocytes/radiation effects , Neodymium/adverse effects , Nevus, Halo/surgery , Skin Transplantation/methods , Yttrium/adverse effects , Adult , Female , Humans , Melanosis/etiology , Melanosis/surgery , Treatment OutcomeABSTRACT
Vitiligo is an asymptomatic but cosmetically disfiguring disorder that results in the formation of depigmented patches on skin and/or mucosae. Vitiligo can be segmental or non-segmental depending upon the morphology of the clinical involvement. It can also be classified as progressing or stable based on the activity of the disease. Further, the extent of involvement can be limited (localized disease) or extensive (generalized disease). The treatment of vitiligo therefore depends on the clinical classification/characteristics of the disease and usually comprises of 2 strategies. The first involves arresting the progression of active disease (to provide stability) in order to limit the area involved by depigmentation. The second strategy aims at repigmentation of the depigmented area. It is also important to maintain the disease in a stable phase and to prevent relapse. Accordingly, a holistic treatment approach for vitiligo should be individualistic and should take care of all these considerations. In this review, we shall discuss the vitiligo treatments and their important clinical and molecular aspects.
Subject(s)
Melanocytes/metabolism , Vitiligo/etiology , Animals , Antioxidants/pharmacology , Antioxidants/therapeutic use , Humans , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Melanocytes/drug effects , Melanocytes/radiation effects , Phototherapy , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Vitiligo/drug therapy , Vitiligo/therapyABSTRACT
When exposed to ultraviolet radiation, the human skin produces profuse reactive oxygen species (ROS), which in turn activate a variety of biological responses. Mounting ROS levels activate tyrosinase by mobilizing α-melanocyte-stimulating hormone in the epidermis and finally stimulates the melanocytes to produce melanin. Meanwhile, the Keap1-Nrf2/ARE pathway, which removes ROS, is activated at increased ROS levels, and antioxidant compounds facilitates the dissociation of Nrf2. In this study, we explored the possible suppressing effects of antioxidant compounds and tyrosine inhibitors on melanin formation and the promotory effects of these compounds on ROS scavenging. The antioxidant activity of glabridin (GLA), resveratrol (RES), oxyresveratrol (OXYR), and phenylethylresorcinol (PR) were investigated via the stable free radical 2,2-diphenyl-1-picrylhydrazyl method. The inhibitory effects of the four compounds and their mixtures on tyrosinase were evaluated. l-Tyrosine or 3-(3,4-dihydroxyphenyl)-l-alanine (l-DOPA) was used as a substrate. The results showed that all mixtures did not exhibit synergistic effects with the l-tyrosine as a substrate, suggesting that l-tyrosine is not suitable as a substrate. However, the mixtures of "GLA:RES," "GLA:OXYR," "OXYR:RES," and "PR:RES" demonstrated synergistic effects (CI < 0.9, p < 0.05), whereas "GLA:RES" and "PR:OXYR" indicated an additive effect (0.9 ditive1, p < 0.05). Furthermore, we used a molecular docking strategy to study the interactions of the four compounds with tyrosinase and l-DOPA. The molecular docking result is consistent with that of the experiment. Finally, we selected RES + OXYR and used PIG1 cells to verify whether OXYR synergistically promotes RES activity on tyrosinase. The two agents had a synergistic inhibitory effect on tyrosinase activity. These results provided a novel synergistic strategy for antioxidants and tyrosinase inhibitors, and this strategy is useful in skin injury treatment.
Subject(s)
Antioxidants/pharmacology , Enzyme Inhibitors/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Plant Extracts/pharmacology , Stilbenes/pharmacology , Antioxidants/chemistry , Drug Synergism , Enzyme Inhibitors/chemistry , Humans , Isoflavones/pharmacology , Kelch-Like ECH-Associated Protein 1/chemistry , Kelch-Like ECH-Associated Protein 1/metabolism , Melanocytes/drug effects , Melanocytes/metabolism , Melanocytes/radiation effects , Molecular Docking Simulation , Monophenol Monooxygenase/chemistry , Monophenol Monooxygenase/metabolism , Phenols/pharmacology , Resorcinols/pharmacology , Resveratrol , Ultraviolet RaysABSTRACT
BACKGROUND: Melasma is a common hyperpigmentation skin disease on face. Light-emitting diode (LED) photomodulation (585nm) is reported to be effective for the treatment of melasma. However, whether and how LED photomodulation would influence melanogenesis of human epidermal melanocytes (HEMs) is unknown. OBJECTIVE: To evaluate the effects of LED photomodulation (585nm) on melanogenesis in HEMs. METHODS: HEMs were irradiated with fluences of 0, 5, 10 and 20J/cm2 585nm LED light. After 5-day treatment, cell viability was analyzed by CCK-8 assay, and apoptosis was assessed by Annexin V APC assay. Melanin content and tyrosinase activity were measured by spectrophotometer. Melanosome stage and autophagosomes were determined under transmission electron microscope (TEM). The formation of autophagic punctate structures was observed under confocal microscope. RT-PCR and western blotting were used to assess the expression of relative mRNA and protein levels. RESULTS: Yellow light LED 585nm had no effects on HEMs cell viability and apoptosis. Treatment with LED 585nm from 5J/cm2 to 20J/cm2 inhibited melanosome maturation, decreased melanin content and tyrosinase activity. Inhibition was accompanied by the decreased expression of tyrosinase (TYR), tyrosinase-related protein-1 (TRP-1) and microphthalmia-associated transcription factor (MITF) on both mRNA and protein levels. Autophagosomes were observed under TEM. Autophagic punctate structures of microtubule-associated protein light chain 3 (LC3) proteins were induced by LED 585nm light. The configuration change of LC3 from LC3-I to LC3-II, and the degradation of p62 protein were observed after LED 585nm. Furthermore, we also revealed that the anti-melanogenic effect of LED 585nm photomodulation was reversed by 3-Methyladenine (3-MA), which inhibits autophagy by blocking autophagosome formation via the inhibition of type III Phosphatidylinositol 3-kinases (PI-3K). CONCLUSIONS: Our finding demonstrated that LED photomodulation with 585nm wavelength suppressed melanin content in HEMs, and the effect was caused by its dose-dependent inhibition on melanogenesis and the induction of HEMs autophagy. This may provide new insights into the efficacy of LED photomodulation in the treatment of hyperpigmentation disorders.