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: 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.

Diet and Vitiligo: The Story So Far.

Vitiligo is an acquired skin pigmentation disease with a global burden of 0.5 to 2 percent of the population. Vitiligo therapy frequently poses a difficulty, which has sparked interest in alternative treatment modalities, including multivitamins and herbal supplementation. It has previously been established that nutrition plays a crucial role in developing, amplifying, or rehabilitating an array of human disorders. However, the correlation between diet diversity and immune-mediated skin diseases is still up to interpretation. Several supplements have been studied, including vitamins, minerals, and herbal supplements. Most studies agree that combining vitamin B12, folic acid, and sun exposure is good for inducing repigmentation. Supplementation of zinc and phenylalanine when used in conjunction with topical steroids or UV-B (ultraviolet B) treatment shows therapeutic effects on vitiligo due to their role in the melanin synthesis pathway. Investigations conducted on herbal supplements have revealed that most of them contain antioxidants, which aid in repigmentation. This narrative review's purpose is to discuss nutrition's function in immune-mediated inflammatory skin diseases from the perspective of the most recent and reliable information available.

Therapeutic Potential of Skin Stem Cells and Cells of Skin Origin: Effects of Botanical Drugs Derived from Traditional Medicine.

Skin, the largest organ of the body, plays a vital role in protecting inner organs. Skin stem cells (SSCs) comprise a group of cells responsible for multiplication and replacement of damaged and non-functional skin cells; thereby help maintain homeostasis of skin functions. SSCs and differentiated cells of the skin such as melanocytes and keratinocytes, have a plethora of applications in regenerative medicine. However, as SSCs reside in small populations in specific niches in the skin, use of external stimulants for cell proliferation in vitro and in vivo is vital. Synthetic and recombinant stimulants though available, pose many challenges due to their exorbitant prices, toxicity issues and side effects. Alternatively, time tested traditional medicine preparations such as polyherbal formulations are widely tested as effective natural stimulants, to mainly stimulate proliferation, and melanogenesis/prevention of melanogenesis of both SSCs and cells of skin origin. Complex, multiple targets, synergistic bioactivities of the phytochemical constituents of herbal preparations amply justify these as natural stimulants. The use of these formulations in clinical applications such as in skin regeneration for burn wounds, wound healing acceleration, enhancement or decrease of melanin pigmentations will be in great demand. Although much multidisciplinary research is being conducted on the use of herbal formulas as stem cell stimulants, very few related clinical trials are yet registered with the NIH clinical trial registry. Therefore, identification/ discovery, in depth investigations culminating in clinical trials, as well as standardization and commercialization of such natural stimulants must be promoted, ensuring the sustainable use of medicinal plants.

Melanoma, Melanin, and Melanogenesis: The Yin and Yang Relationship.

Melanin pigment plays a critical role in the protection against the harmful effects of ultraviolet radiation and other environmental stressors. It is produced by the enzymatic transformation of L-tyrosine to dopaquinone and subsequent chemical and biochemical reactions resulting in the formation of various 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI) oligomers-main constituents of eumelanin, and benzothiazine and benzothiazole units of pheomelanin. The biosynthesis of melanin is regulated by sun exposure and by many hormonal factors at the tissue, cellular, and subcellular levels. While the presence of melanin protects against the development of skin cancers including cutaneous melanoma, its presence may be necessary for the malignant transformation of melanocytes. This shows a complex role of melanogenesis in melanoma development defined by chemical properties of melanin and the nature of generating pathways such as eu- and pheomelanogenesis. While eumelanin is believed to provide radioprotection and photoprotection by acting as an efficient antioxidant and sunscreen, pheomelanin, being less photostable, can generate mutagenic environment after exposure to the short-wavelength UVR. Melanogenesis by itself and its highly reactive intermediates show cytotoxic, genotoxic, and mutagenic activities, and it can stimulate glycolysis and hypoxia-inducible factor 1-alpha (HIF-1α) activation, which, combined with their immunosuppressive effects, can lead to melanoma progression and resistance to immunotherapy. On the other hand, melanogenesis-related proteins can be a target for immunotherapy. Interestingly, clinicopathological analyses on advanced melanomas have shown a negative correlation between tumor pigmentation and diseases outcome as defined by overall survival and disease-free time. This indicates a "Yin and Yang" role for melanin and active melanogenesis in melanoma development, progression, and therapy. Furthermore, based on the clinical, experimental data and diverse effects of melanogenesis, we propose that inhibition of melanogenesis in advanced melanotic melanoma represents a realistic adjuvant strategy to enhance immuno-, radio-, and chemotherapy.

Current Debates on Etiopathogenesis and Treatment Strategies for Vitiligo.

Vitiligo is an acquired, chronic, and progressive depigmentation or hypopigmentation characterized by the destruction of melanocytes and the occurrence of white patches or macules in the skin, mucosal surface of eyes, and ears. Melanocytes are the melanin pigment-producing cells of the skin which are destroyed in pathological conditions called vitiligo. Approximately 0.5 - 2.0% of the population is suffering from vitiligo, and a higher prevalence rate of up to 8.8% has been reported in India. It is caused by various pathogenic factors like genetic predisposition, hyperimmune activation, increased oxidative stress, and alteration in neuropeptides level. Genetic research has revealed a multi- genetic inheritance that exhibits an overlap with other autoimmune disorders. However, melanocytes specific genes are also affected (such as DDR1, XBP1, NLRP1, PTPN22, COMT, FOXP3, ACE, APE, GSTP1, TLR, SOD, and CTLA-4). A number of therapeutic options are employed for the treatment of vitiligo. The topical corticosteroids and immunomodulators are currently in practice for the management of vitiligo. Phototherapies alone and in combinations with other approaches are used in those patients who do not respond to the topical treatment. The main focus of this review is on the etiopathological factors, pharmacological management (phototherapy, topical, systemic, and surgical therapy), and herbal drugs used to treat vitiligo.

Invitro effect of pine bark extract on melanin synthesis, tyrosinase activity, production of endothelin-1, and PPAR in cultured melanocytes exposed to Ultraviolet, Infrared, and Visible light radiation.

BACKGROUND: French maritime pine bark (Pinus pinaster) extract (PBE), the registered trade name of which is Pycnogenol® , has been studied for its depigmenting action due to its antioxidant, anti-inflammatory, and anti-melanogenic activity. However, the mechanisms through which PBE are still not fully clear. OBJECTIVE: Evaluate the impact of PBE on four in vitro parameters closely associated with cutaneous pigmentation, including melanin synthesis, tyrosinase activity, endothelin-1 (ED1), and production of peroxisome proliferator-activated receptor α, δ, and γ (PPAR α, δ, and γ), by studying the modulation of action of ultraviolet radiation A (UVA)/ultraviolet radiation B (UVB), infrared-A (IR-A), visible light (VL), and association of UVA/UVB, IR-A, and VL (ASS). METHODS: Human melanocytes were incubated in a dry extract solution of PBE, exposed to UVA/UVB, IR-A, VL, and ASS for subsequent quantification of melanin, ED1, and PPAR α, δ, and γ. The effects of PBE on inhibition of tyrosinase activity were also performed by monophenolase activity assay. RESULTS: UVA/UVB, IR-A, VL, and ASS radiation caused significant increases in the synthesis of melanin, ED1, and PPAR α, δ, and γ when compared to baseline control. However, PBE significantly reduced the production of melanin, ED1, and PPAR α, δ, and γ, as well as reducing about 66.5% of the tyrosinase activity. CONCLUSIONS: PBE reduces in vitro melanin production by downregulating tyrosinase and reducing pigmentation-related mediators, such as ED1 and PPAR α, δ, and γ, therefore contributing to the inhibition of pathways associated with skin hyperpigmentation.

Genetic Background Influences Severity of Colonic Aganglionosis and Response to GDNF Enemas in the Holstein Mouse Model of Hirschsprung Disease.

Hirschsprung disease is a congenital malformation where ganglia of the neural crest-derived enteric nervous system are missing over varying lengths of the distal gastrointestinal tract. This complex genetic condition involves both rare and common variants in dozens of genes, many of which have been functionally validated in animal models. Modifier loci present in the genetic background are also believed to influence disease penetrance and severity, but this has not been frequently tested in animal models. Here, we addressed this question using Holstein mice in which aganglionosis is due to excessive deposition of collagen VI around the developing enteric nervous system, thereby allowing us to model trisomy 21-associated Hirschsprung disease. We also asked whether the genetic background might influence the response of Holstein mice to GDNF enemas, which we recently showed to have regenerative properties for the missing enteric nervous system. Compared to Holstein mice in their original FVB/N genetic background, Holstein mice maintained in a C57BL/6N background were found to have a less severe enteric nervous system defect and to be more responsive to GDNF enemas. This change of genetic background had a positive impact on the enteric nervous system only, leaving the neural crest-related pigmentation phenotype of Holstein mice unaffected. Taken together with other similar studies, these results are thus consistent with the notion that the enteric nervous system is more sensitive to genetic background changes than other neural crest derivatives.

Herb Sanqi-Derived Compound K Alleviates Oxidative Stress in Cultured Human Melanocytes and Improves Oxidative-Stress-Related Leukoderma in Guinea Pigs.

Sanqi, a traditional Chinese herb, is widely used for cardiovascular diseases, and its neuroprotective effects against oxidative stress were recently discovered. The purpose of this study was to investigate whether Sanqi-derived compound K (Sanqi-CK), an active metabolite of Sanqi, could protect melanocytes from oxidative stress. Cultured human primary skin epidermal melanocytes (HEMn-MPs) were treated with hydrogen peroxide (H2O2) in the presence or absence of Sanqi-CK. Sanqi-CK exhibited protective effects against H2O2-induced cell death by reducing oxidative stress. In addition, treatment with Sanqi-CK reversed the decreased glutathione reductase activity and decreased ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) seen in H2O2-treated melanocytes. Furthermore, topical application of Sanqi-CK alleviated leukoderma in guinea pigs, a disorder characterized by melanocyte cell death resulting from rhododendrol-induced oxidative stress. Taken together, these data suggest that Sanqi-CK protects melanocytes against oxidative stress, and its protective effects are associated with modulating the redox balance between GSH and GSSG and activating glutathione reductase. Thus, Sanqi-CK may be a good candidate for preventing melanocyte loss in oxidative-stress-associated pigmentary disorders.

Evaluation of Chemical Composition, Radical Scavenging and Antitumor Activities of Satureja hortensis L. Herb Extracts.

Satureja hortensis L. is an annual herbaceous plant of the Lamiaceae Lindl. family. S. hortensis L., related to thyme and rosemary, is used as spice and traditional medicinal herb in Europe. Mainly due to the polyphenols contained in S. hortensis L., this plant exhibits multiple biological effects. However, therapeutic effects on cells, including skin tumors, have not yet been studied. Therefore, the aim of this study was to compare the composition and the resulting antioxidant as well as biological properties [on melanocytes and melanoma cells] of summer, savory growing in botanical garden of Vytautas Magnus University in middle Lithuania climatic conditions, collected during various phases of vegetation. It has been shown that the budding phase alcohol extract of this plant contains the largest amounts of polyphenols, including rutin and rosemary acid, which promote the radical scavenging activity and antioxidant properties. In contrast, the extract from the massive flowering phase already at a concentration of 12.5 µg/mL reduces the survival of melanoma cells to 60% with 90% melanocytes survival. In addition, extracts from beginning of flowering and end of flowering at a concentration of 25 µg/mL, containing significantly less rutin and rosmarinic acid, in combination with irradiation of cells with UVB, significantly increased the lipid peroxidation process, particularly in melanoma cells. These data indicate the possibility of using extracts from S. hortensis L. to modulate/differentiate the metabolism of normal and tumor skin cells.

Therapeutic implications of assessment of serum zinc levels in patients with vitiligo: A patient controlled prospective study.

Vitiligo is an autoimmune disease characterized by patches of depigmentation. Zinc is an antiapoptotic molecule that exhibits antioxidant properties. The study aimed to investigate the serum levels of zinc in vitiligo patients compared to healthy controls and to whether exists a correlation between disease severity and serum levels of zinc. Fifty patients with vitilgo (group A) and 50 age and sex matched healthy controls (group B) were recruited and serum zinc level was measured using atomic absorption spectrophotometry and results were compared and correlated to each other and to disease severity and extension. The mean serum zinc levels in group A was 50.93 ± 11.02 in comparison to a mean of 77.09 ± 12.16 in group B (P = .049, T = -1.993). Vitiligo area severity index (VASI) scores in the vitiligo group ranged from 0.5 to 27 with a mean ± SD of (9.19 ± 4.47). A high statistically significant negative correlation was demonstrated between serum zinc levels and the extension of vitiligo (P value = .0001 and R value = - 0.835). A significant association exists between vitiligo and serum zinc levels. Serum zinc levels correlated negatively with vitiligo disease severity and extension. Zinc supplementation and use can be of potential importance in setting vitiligo treatment protocols.

42 °C heat stress pretreatment protects human melanocytes against 308-nm laser-induced DNA damage in vitro.

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.

Homocysteine induces melanocytes apoptosis via PERK-eIF2α-CHOP pathway in vitiligo.

Vitiligo is a depigmentation disorder that develops as a result of the progressive disappearance of epidermal melanocytes. The elevated level of amino acid metabolite homocysteine (Hcy) has been identified as circulating marker of oxidative stress and known as a risk factor for vitiligo. However, the mechanism underlying Hcy-regulated melanocytic destruction is currently unknown. The present study aims to elucidate the effect of Hcy on melanocytic destruction and its involvement in the pathogenesis of vitiligo. Our results showed that Hcy level was significantly elevated in the serum of progressive vitiligo patients. Notably, Hcy induced cell apoptosis in melanocytes via activating reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α)-C/EBP homologous protein (CHOP) pathway. More importantly, folic acid, functioning in the transformation of Hcy, could lower the intracellular Hcy level and further reverse the apoptotic effect of Hcy on melanocytes. Additionally, Hcy disrupted melanogenesis whereas folic acid supplementation could reverse the melanogenesis defect induced by Hcy in melanocytes. Taken together, Hcy is highly increased in vitiligo patients at progressive stage, and our in vitro studies revealed that folic acid could protect melanocytes from Hcy-induced apoptosis and melanin synthesis inhibition, indicating folic acid as a potential benefit agent for patients with progressive vitiligo.

NB-UVB Induces Melanocytic Differentiation of Human Hair Follicle Neural Crest Stem Cells.

BACKGROUND: Phototherapy is an important method to treat vitiligo. However, it is unclear how phototherapy affects melanocyte precursors and skin neural crest stem cells. OBJECTIVE: To investigate the underlying mechanisms of narrow-band ultraviolet B (NB-UVB) induced melanocyte lineage differentiated from human scalp-derived neural crest stem cells (HS-NCSCs). METHODS: HS-NCSCs were expanded from scalp hair follicles. The c-Kit-/CD57- HS-NCSCs were isolated by cell sorting. Different doses of NB-UVB were used to irradiate these HS-NCSCs. Cell ultrastructure was examined by transmission electron microscope. Melanocyte marker expression was analyzed by Quantitative RT-PCR and Western blot. Cell proliferation and migration were also evaluated. RESULTS: The c-Kit-/CD57- HS-NCSCs expressed embryonic NCSC biomarkers. NB-UVB at a dose of 100 mJ of NB-UVB had little effect on the cell proliferation of differentiated melanocytes from c-Kit-/CD57- HS-NCSCs, while 700 mJ inhibited cell proliferation significantly. The dendritic processes of differentiated melanocytes increased after radiation. The tyrosinase and Melanocortin 1 receptor (Mc1R) expression of differentiated melanocytes increased after NB-UVB exposure. The effect of NB-UVB on tyrosinase expression was modulated by signaling inhibitors H89 and PD98059 as well as Mc1R level in the cells. The migration ability of differentiated melanocytes was enhanced under 100 mJ exposure. CONCLUSION: These data demonstrate that NB-UVB facilitates melanocytic differentiation of the HS-NCSCs and enhances migration of these cells. Mc1R and cAMP pathway play a critical role in NB-UVB induced melanocytic differentiation.

Transcriptome Analysis of the Breast Muscle of Xichuan Black-Bone Chickens Under Tyrosine Supplementation Revealed the Mechanism of Tyrosine-Induced Melanin Deposition.

The Xichuan black-bone chicken, which is a rare local chicken species in China, is an important genetic resource of black-bone chickens. Tyrosine can affect melanin production, but the molecular mechanism underlying tyrosine-induced melanin deposition in Xichuan black-bone chickens is poorly understood. Here, the blackness degree and melanin content of the breast muscle of Xichuan black-bone chickens fed a basic diet with five levels of added tyrosine (i.e., 0.2, 0.4, 0.6, 0.8, and 1.0%; these groups were denoted test groups I-V, respectively) were assessed, and the results showed that 0.8% tyrosine was the optimal level of added tyrosine. Moreover, the effects of tyrosine supplementation on the proliferation and tyrosinase content of melanocytes in Xichuan black-bone chickens were evaluated. The results revealed a dose-dependent relationship between tyrosine supplementation and melanocyte proliferation. In addition, 417 differentially expressed genes (DEGs), including 160 upregulated genes and 257 downregulated genes, were identified in a comparative analysis of the transcriptome profiles constructed using the pooled total RNA from breast muscle tissues of the control group and test group IV, respectively (fold change ≥2.0, P < 0.05). These DEGs were mainly involved in melanogenesis, the calcium signaling pathway, the Wnt signaling pathway, the mTOR signaling pathway, and vascular smooth muscle contraction. The pathway analysis of the DEGs identified some key genes associated with pigmentation, such as DCT and EDNRB2. In summary, the melanin content of breast muscle could be markedly enhanced by adding an appropriate amount of tyrosine to the diet of Xichuan black-bone chickens, and the EDNRB2-mediated molecular regulatory network could play a key role in the biological process of tyrosine-induced melanin deposition. These results have deepened the understanding of the molecular regulatory mechanism of melanin deposition in black-bone chickens and provide a basis for the regulation of nutrition and genetic breeding associated with melanin deposition in Xichuan black-bone chickens.

Changes in melanocyte RNA and DNA methylation favour pheomelanin synthesis and may avoid systemic oxidative stress after dietary cysteine supplementation in birds.

Cysteine plays essential biological roles, but excessive amounts produce cellular oxidative stress. Cysteine metabolism is mainly mediated by the enzymes cysteine dioxygenase and γ-glutamylcysteine synthetase, respectively coded by the genes CDO1 and GCLC. Here we test a new hypothesis posing that the synthesis of the pigment pheomelanin also contributes to cysteine homeostasis in melanocytes, where cysteine can enter the pheomelanogenesis pathway. We conducted an experiment with the Eurasian nuthatch Sitta europaea, a bird producing large amounts of pheomelanin for feather pigmentation, to investigate if melanocytes show epigenetic lability under exposure to excess cysteine. We increased systemic cysteine levels in nuthatches by supplementing them with dietary cysteine during growth. In feather melanocytes this led to the downregulation of genes involved in intracellular cysteine metabolism (GCLC), cysteine transport to the cytosol from the extracellular medium (Slc7a11) and from melanosomes (CTNS), and regulation of tyrosinase activity (MC1R and ASIP). These changes were mediated by increases in DNA m5 C in all genes except Slc7a11, which experienced RNA m6 A depletion. Birds supplemented with cysteine synthesized more pheomelanin than controls, but did not suffer higher systemic oxidative stress. These results suggest that excess cysteine activates an epigenetic mechanism that favours pheomelanin synthesis and may protect against oxidative stress.

Role of IL-17A receptor blocking in melanocyte survival: A strategic intervention against vitiligo.

Cytokines regulate immune response and inflammation and play an important role in depigmentation process of an autoimmune disease, vitiligo. We sought to determine how inflammatory cytokines influence the progression of vitiligo, and based on that, we develop a logical therapeutic intervention using primary melanocyte culture. Melanocytes were cultured and exposed to IL-17A, IL-1ß, IFN-γ and TGF-ß for 4 days. Melanocytes proliferation, tyrosinase assay and melanin content were measured. Real-Time PCR was used to analyse mRNA expression of genes specific for melanocytes growth and pigmentation. Anti-IL-17A receptor antibody was used to block IL-17A receptors expressed on melanocytes. Protein expression of MITF and TYR was assessed by immunofluorescence and Western blotting. A gradual decline in the melanocyte population, melanin content and tyrosinase activity was observed after different cytokine treatment. The expression of MITF and its downstream genes after blocking with anti-IL-17RA, an increased melanin content, increased expression of TYR, MITF along with its downstream genes, and cell proliferation was observed.

Cytokines: the yin and yang of vitiligo pathogenesis.

INTRODUCTION: Dysregulation of melanocyte function is associated with vitiligo, an idiopathic autoimmune hypopigmentary skin disorder, caused by the selective destruction of melanocytes. Cytokines, the key mediators of immune response, which are pivotal in maintaining immune homeostasis, are crucial in vitiligo pathogenesis. Several studies indicate that there is an imbalance between pro- and anti-inflammatory cytokines in the skin and serum of vitiligo patients. Areas covered: In this comprehensive review, we have summarized the correlation of cytokine imbalance and vitiligo pathogenesis, its role in melanocyte biology, and its impact on vitiligo treatment. We have integrated various published reports on the levels of major cytokines from skin and serum samples of vitiligo patients. We have also discussed the role of endoplasmic reticulum and oxidative stress on cytokine imbalance and vice versa leading to destruction of melanocytes. Expert commentary: The review reflects that dysregulation of cytokines is multifactorial, ranging from genetic predisposition to altered protein expression relevant to vitiligo pathogenesis. We emphasize that cytokine imbalance in systemic and skin microenvironment plays a crucial role in vitiligo pathogenesis and has promising potential as therapeutic targets for vitiligo.

Melanocyte activation and skin barrier disruption induced in melasma patients after 1064 nm Nd:YAG laser treatment.

Melasma is a frequently acquired hyperpigmentary skin disorder, for which several therapies are available. Among them, 1064 nm QS Nd:YAG laser therapy is an effective method, but the recurrence rate of laser treatment is still high. The aim of the present study was to elucidate the mechanism of the high relapse rate of melasma after 1064 nm Nd:YAG laser treatment. Twenty-five female melasma patients were treated with 1064 nm Nd:YAG laser for 10 times. The lesional skin and non-lesional skin were evaluated by means of a reflectance confocal laser scanning microscope before and after laser treatment. Melanin content and transepidermal water loss (TEWL) were measured by an MPA9 skin multifunction tester accordingly. The melanin index value was significantly decreased in the lesional skin after laser treatment, while the non-lesional skin had no difference. The dendritic cells were observed at the level of the dermal-epidermal junction (DEJ) in the lesions of 8 patients before laser treatment, while after laser treatment, the dendritic cells were observed in all 25 subjects. Moreover, there was significant difference between the TEWL value of the lesions before and after laser treatment. Furthermore, the TEWL value was higher in lesions of the 8 subjects which had dendritic cells compared with other 17 subjects which had no dendritic cells, no matter before or after laser treatment. The relapse patients of melasma had higher TEWL value compared with the non-relapse patients. Melanocyte activation and skin barrier disruption may be related to the high relapse rate of melasma after laser treatment.

Effect of puerarin on melanogenesis in human melanocytes and vitiligo mouse models and the underlying mechanism.

Puerarin is the major bioactive ingredient derived from the root of the Pueraria lobata (Willd.), and its antioxidative stress effects have been demonstrated in several previous studies. Moreover, Puerarin can upregulate melanin synthesis and microphthalmia-associated transcription factor (MITF) transcription by increasing cAMP level of intracellular cyclic adenosine monophosphate. Vitiligo is an acquired cutaneous disorder of pigmentation, and the pathogenesis has remained elusive. Current treatment modalities are directed towards achieving repigmentation. In this study, we found that after treating with puerarin at various concentrations of 40 µmol/L, the melanin content of human melanocytes increased significantly and the apparent level of protein and the RNA levels of MITF, tyrosinase (TYR), and tyrosinase-related protein 1 (TRP-1) were also increased. Further, puerarin was shown to inhibit phosphorylation and activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) without significantly affecting p38 and c-Jun N-terminal kinase phosphorylation. These results demonstrated that puerarin stimulated melanogenesis in human melanocytes via inhibition of ERK1/2 signaling pathways, which leads to upregulation of MITF and TYR as well as TRP-1 subsequently. Additionally, mice vitiligo models with puerarin treatment showed lighter pathological changes. Therefore, we suggested that puerarin might be a potential medicine for vitiligo.