Melanocyte Migration Research Articles

The Microneedle Revolution: Transforming Vitiligo Treatment Landscapes-A Comprehensive Review of the Literature.

Vitiligo is characterized by the emergence of depigmented patches on the skin, posing significant therapeutic challenges. Microneedling, a novel treatment strategy, capitalizes on its potential to invigorate skin regeneration and facilitate melanocyte migration. This review critically evaluates the efficacy, safety, and patient satisfaction associated with microneedling for vitiligo treatment, juxtaposing it with traditional therapies to elucidate its viability as either a standalone or complementary treatment modality. A comprehensive literature review was conducted across major databases, including PubMed and Cochrane Library, using keywords like "microneedling" and "vitiligo," encompassing studies up to January 2024. This review focused on microneedling's effectiveness, safety, and patient satisfaction, including both solo and combined treatments. Data synthesis emphasized repigmentation rates, side effects, and patient feedback. An exhaustive review of studies pertaining to microneedling for vitiligo, especially focusing on outcomes when administered alone or in conjunction with agents such as tacrolimus and 5-fluorouracil, was undertaken. Key evaluation metrics included repigmentation success rates, adverse effects, and patient-reported outcomes. Microneedling demonstrates a favourable safety profile, with mild and manageable side effects such as pain, erythema, and temporary hyperpigmentation. Severe adverse events are rare, further supporting its safety as a treatment option for vitiligo. The evidence amassed suggests that microneedling significantly augments repigmentation rates, particularly in synergy with topical treatments. It is generally well-tolerated, manifests minimal adverse effects, and has garnered high patient satisfaction levels. Nonetheless, the absence of standardized treatment protocols and paucity of long-term efficacy data underscore the imperative for further empirical inquiry. Microneedling emerges as a propitious treatment alternative for vitiligo, demonstrating both safety and efficacy, notably when used in tandem with topical agents. Future investigations should aim at protocol standardization and long-term efficacy evaluation to firmly establish its therapeutic stature within vitiligo management paradigms.

Modulatory effects of oxytocin on normal human cultured melanocyte proliferation, migration, and melanogenesis

Melanocytes are specialized melanin-producing neural crest-derived cells. Melanocyte proliferation and melanin production (i.e., melanogenesis) are crucial for determining skin color. Disruption of these processes can cause pigmentary skin disorders, including hypo-pigmentary disorders such as vitiligo and hyper-pigmentary disorders such as melasma. Understanding these processes is important for discovering new targets to tackle these skin disorders. Therefore, this study aimed to investigate the effects of oxytocin (OXT) on melanocyte functions. Normal Human Cultured Melanocytes (NHCM) were treated with different OXT doses to investigate OXT effects and mechanisms on NHCM proliferation, migration, and on melanogenesis. OXT significantly increased NHCM proliferation and migration in a dose-dependent manner after 72 h of treatment. In addition, OXT dose-dependently upregulated melanogenesis-related microphtalmia-associated transcription factor, tyrosinase, tyrosinase-related protein (TYRP)-1, and TYRP-2 expression accompanied by an increased trend in melanosome number and maturation stage. Furthermore, OXT at concentrations (62.5–125 nM) increased melanin production. These findings suggest the involvement of OXT receptor (OXTR). In addition, this study demonstrates that OXT stimulates melanocyte proliferation, migration, with a tendency toward melanosome maturation, while it modulates melanin production in a dose-dependent manner. Thus, OXT system including its receptor OXTR may be a potential therapeutic target for skin pigmentary disorders.

Transcriptome-based screening and validation of key genes for wool color in cashmere goats.

Colored wool from cashmere goats is increasingly popular among consumers, but the transcriptomic differences between coat colors are poorly understood. This study aimed to screen for coat color regulation-associated genes in cashmere goats to ascertain their underlying molecular mechanisms. Transcriptomic sequencing of skin tissues from black (BC), brown (YC), and white cashmere (WC) goats was performed. Immunohistochemistry and western blotting were used to validate SLC24A4 and DCT expression, two essential genes identified for coat color determination. We identified 6,518 differentially expressed genes (DEGs) in the BC vs. WC group (3,919 upregulated, 2,599 downregulated). Next, 5,593 DEGs were identified in the YC vs. WC group (3,629 upregulated, 1,964 downregulated). Finally, 4,538 DEGs were expressed in both groups, with 1,980 and 1,055 DEGs exclusively expressed in either group. Functions and pathways associated with hair color were enriched, including melanosomes, melanocyte migration, melanin biosynthesis processes and functions, and melanogenesis pathways. TYRP1, SLC24A4, PMEL, OCA2, and DCT were significantly upregulated in BC goat skin, while ASIP was significantly upregulated in YC skin. Additionally, KIT, POMC, SLC24A5, Wnt3a, and EDN3 were DEGs for different coat colors. Immunohistochemistry revealed SLC24A4 and DCT expression in dermal papillae, inner and outer root sheaths, and the hair follicle matrix. Western blotting showed that SLC24A4 protein levels were highest in BC goat skin. DCT protein levels were also highest in BC goat skin, albeit not significantly. These results further our understanding of coat color regulation in cashmere goats, establishing a foundation for their molecular breeding.

Melanocyte lineage dynamics in development, growth and disease.

Melanocytes evolved to produce the melanin that gives colour to our hair, eyes and skin. The melanocyte lineage also gives rise to melanoma, the most lethal form of skin cancer. The melanocyte lineage differentiates from neural crest cells during development, and most melanocytes reside in the skin and hair, where they are replenished by melanocyte stem cells. Because the molecular mechanisms necessary for melanocyte specification, migration, proliferation and differentiation are co-opted during melanoma initiation and progression, studying melanocyte development is directly relevant to human disease. Here, through the lens of advances in cellular omic and genomic technologies, we review the latest findings in melanocyte development and differentiation, and how these developmental pathways become dysregulated in disease.

Analysis of the Skin and Brain Transcriptome of Normally Pigmented and Pseudo-Albino Southern Flounder (Paralichthys lethostigma) Juveniles to Study the Molecular Mechanisms of Hypopigmentation and Its Implications for Species Survival in the Natural Environment.

Southern flounder skin pigmentation is a critical phenotypic characteristic for this species' survival in the natural environment. Normal pigmentation allows rapid changes of color for concealment to capture prey and UV light protection. In contrast, highly visible hypopigmented pseudo-albinos exhibit a compromised immune system and are vulnerable to predation, sensitive to UV exposure, and likely have poor survival in the wild. Skin and brain tissue samples from normally pigmented and hypopigmented individuals were analyzed with next-generation RNA sequencing. A total of 1,589,613 transcripts were used to identify 952,825 genes to assemble a de novo transcriptome, with 99.43% of genes mapped to the assembly. Differential gene expression and gene enrichment analysis of contrasting tissues and phenotypes revealed that pseudo-albino individuals appeared more susceptible to environmental stress, UV light exposure, hypoxia, and osmotic stress. The pseudo-albinos' restricted immune response showed upregulated genes linked to cancer development, signaling and response, skin tissue formation, regeneration, and healing. The data indicate that a modified skin collagen structure likely affects melanocyte differentiation and distribution, generating the pseudo-albino phenotype. In addition, the comparison of the brain transcriptome revealed changes in myelination and melanocyte stem cell activity, which may indicate modified brain function, reduced melanocyte migration, and impaired vision.

Pigment epithelium derived factor drives melanocyte proliferation and migration in neurofibromatosis café au lait macules.

RASopathies, which include neurofibromatosis type 1 (NF1), are defined by Ras/mitogen-activated protein kinase (Ras/MAPK) pathway activation. They represent a group of clinically related disorders often characterised by multiple Café au Lait Macules (CALMs). To determine, using in depth transcriptomic analysis of NF1 melanocytes from CALM and unaffected skin, (1) the gene(s) responsible for melanocyte proliferation and migration, and (2) the activated signalling pathway(s) in NF1 melanoma. Classical NF1 (n=2, who develop tumours) and 3bp deletion NF1 (p. Met992del, who do not develop tumours) (n=3) patients underwent skin biopsies from CALM and unaffected skin. Melanocytes were isolated and propagated, with five replicates from each tissue sample. DNA and RNA were extracted for mutational analysis and transcriptomic profiling with six replicates per sample. Mechanistic determination was undertaken using melanocyte and melanoma cell lines. All CALMs in NF1 were associated with biallelic NF1 loss, resulting in amplification of Ras/MAPK and Wnt pathway signalling. CALMs were also associated with reduced SERPINF1 gene expression (and pigment epithelium-derived factor (PEDF) levels, the reciprocal protein), a known downstream target of the master regulator of melanocyte differentiation microphthalmia-associated transcription factor (MITF), leading to increased melanocyte proliferation, migration and invasion. In classical NF1 and melanoma, but not 3bp deletion NF1, there was also activation of the PI3K/AKT pathway. Pigment epithelium-derived factor was found to reduce cell proliferation and invasion of NF1 melanoma. Melanocyte proliferation and migration leading to CALMs in NF1 arises from biallelic NF1 loss, resulting in RAS/MAPK pathway activation, and reduced expression of the tumour suppressor PEDF. Activation of the PI3K/AKT pathway in classical NF1 and NF1 melanoma may facilitate tumour growth.

Receptor tyrosine kinase inhibition leads to regression of acral melanoma by targeting the tumor microenvironment.

Acral melanoma (AM) is an aggressive melanoma variant that arises from palmar, plantar, and nail unit melanocytes. Compared to non-acral cutaneous melanoma (CM), AM is biologically distinct, has an equal incidence across genetic ancestries, typically presents in advanced stage disease, is less responsive to therapy, and has an overall worse prognosis. Independent analysis of published genomic and transcriptomic sequencing identified that receptor tyrosine kinase (RTK) ligands and adapter proteins are frequently amplified, translocated, and/or overexpressed in AM. To target these unique genetic changes, a zebrafish acral melanoma model was exposed to a panel of narrow and broad spectrum multi-RTK inhibitors, revealing that dual FGFR/VEGFR inhibitors decrease acral-analogous melanocyte proliferation and migration. The potent pan-FGFR/VEGFR inhibitor, Lenvatinib, uniformly induces tumor regression in AM patient-derived xenograft (PDX) tumors but only slows tumor growth in CM models. Unlike other multi-RTK inhibitors, Lenvatinib is not directly cytotoxic to dissociated AM PDX tumor cells and instead disrupts tumor architecture and vascular networks. Considering the great difficulty in establishing AM cell culture lines, these findings suggest that AM may be more sensitive to microenvironment perturbations than CM. In conclusion, dual FGFR/VEGFR inhibition may be a viable therapeutic strategy that targets the unique biology of AM.

Effects of EGFR-TKI on epidermal melanin unit integrity: Therapeutic implications for hypopigmented skin disorders.

Epidermal melanin unit integrity is crucial for skin homeostasis and pigmentation. Epidermal growth factor (EGF) receptor (EGFR) is a pivotal player in cell growth, wound healing, and maintaining skin homeostasis. However, its influence on skin pigmentation is relatively unexplored. This study investigates the impact and underlying mechanisms of EGFR inhibitors on skin pigmentation. We evaluated EGF and EGFR expression in various skin cells using quantitative real-time PCR, Western blot, and immunofluorescence. EGF and EGFR were predominantly expressed in epidermal keratinocytes, and treatment with the EGFR tyrosine kinase inhibitors (EGFR-TKIs) gefitinib and PD153035 significantly increased stem cell factor (SCF) and endothelin-1 (ET-1) expression in cultured keratinocytes. Enhanced melanocyte migration and proliferation were observed in co-culture, as evidenced by time-lapse live imaging and single-cell tracking assays. Furthermore, topical application of gefitinib to guinea pig dorsal skin induced increased pigmentation and demonstrated efficacy in mitigating rhododendrol-induced leukoderma. Suppression of EGF signaling indirectly enhanced skin pigmentation by upregulating SCF and ET-1 in epidermal keratinocytes. This novel mechanism highlights the pivotal role of EGF signaling in regulating skin pigmentation, and topical EGFR-TKI therapy at an appropriate dose may be a promising approach for depigmentation disorder management.

Combination of 308-nm excimer laser and piperine promotes melanocyte proliferation, migration, and melanin content production via the miR-328/SFRP1 axis.

Both piperine and a 308-nm excimer laser have significant curative effects on vitiligo. This study mainly explored the molecular mechanism of a 308-nm excimer combined with piperine in regulating melanocyte proliferation. Epidermal melanocytes were cultured in piperine solution, and the cells were irradiated by an XTRAC excimer laser treatment system at 308-nm output monochromatic light. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were for detecting the expression levels of genes or proteins. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and Transwell method was for assessing cell viability and migration capacity. The content of melanin was also detected. The combination of the 308-nm excimer laser and piperine enhanced the cell proliferation, migration, and melanin production of melanocytes and upregulated the level of miR-328, and restraint of miR-328 reversed the influence of the 308-nm excimer laser and piperine. Secreted frizzled-related protein 1 (SFRP1) is a direct target gene of miR-328, and miR-328 can inhibit the expression of SFRP1 and elevate the protein level of the Wnt/β-catenin signaling pathway. The 308-nm excimer laser combined with piperine may be more efficient than piperine alone in the remedy of vitiligo, and the miR-328/SFRP1 and Wnt/β-catenin pathways are participated in the proliferation, migration, and melanin synthesis of melanocytes.

Primary endobronchial melanoma: a case report and clinical management indications

BackgroundWhile cutaneous melanomas are well-documented, primary melanoma of the lung (PMML), particularly with endobronchial origin, remains rare and poorly characterized. This case report addresses gaps in understanding by presenting a comprehensive case of a 71-year-old male with primary endobronchial melanoma and conducting a systematic review of PMML cases.Case PresentationThe patient, a former smoker, presented with dyspnea, cough, and hemoptysis. Imaging revealed left lung atelectasis and a suspicious nodule. Bronchoscopy identified an endobronchial mass, subsequently treated with argon plasma coagulation and resection. Biopsy confirmed melanoma. Extensive examinations ruled out a primary skin lesion. Despite initial treatment, recurrence led to pneumonectomy. Histopathology confirmed melanoma. The patient received treatment with pembrolizumab and ipilimumab, but with poor clinical benefit.ConclusionsPrimary endobronchial melanoma is a rare entity, comprising 0.01% of lung tumors. This case underscores diagnostic challenges and emphasizes histological criteria to distinguish primary from metastatic lesions. The pathogenesis remains unclear, with theories proposing foetal melanocyte migration or squamous metaplasia. Prognosis varies, necessitating radical surgical extirpation. A systematic review revealed diverse outcomes, supporting the need for further research. In conclusion, endobronchial melanoma involves an endoscopic and surgical management, but evolving therapies, such as immunotherapy, may reshape treatment paradigms. This case contributes to our understanding of PMML, guiding future research and clinical management. As therapeutic options evolve, continued research is crucial to refine our understanding and improve outcomes for this rare malignancy.

Investigation of the pathogenesis of ADAR1 gene in dyschromatosis symmetrica hereditaria.

The pathogenesis of dyschromatosis symmetrica hereditaria (DSH) has not been well defined. In this study, we sought to investigate the influence of the ADAR1 gene on DSH both invitro and invivo. Morpholino knockdown of adar1 in zebrafish produced phenotypes characterized by polarity changes, and abnormal migration and distribution of melanocytes. Differential expression of C-KIT and distinct patterns of apoptosis between hyperpigmented and hypopigmented areas in DSH patient were detected by means of immunohistochemical methods and TUNEL assays, respectively. This study revealed that adar1 knockdown in a zebrafish model resulted in abnormal migration and changes in the cell polarity of melanocytes, and provided novel insight into the mechanism of DSH pathogenesis.

TNF Signaling Deficiency Promotes UVB-Induced Melanocyte Stem Cell Activation and Migration

TNF Signaling Deficiency Promotes UVB-Induced Melanocyte Stem Cell Activation and Migration

Decreased ZMIZ1 suppresses melanogenesis in vitiligo by regulating mTOR/AKT/GSK-3β-mediated glucose uptake.

The loss of epidermal melanocytes is a distinguishing feature of vitiligo (VIT), a prevalent and long-lasting skin ailment. While various hypotheses exist to explain the cause of VIT, the precise mechanisms leading to this disease remain unclear. Zinc finger MIZ-type containing 1 (ZMIZ1) has a strong link with the development and occurrence of VIT. However, the exact role of ZMIZ1 and its underlying mechanisms in VIT are not well understood. Our study aims to illustrate that targeting ZMIZ1 is an effective therapeutic and prophylactic strategy for treating VIT. We obtained the RNA expression profile of VIT samples using RNA-seq and determined the locations and expression of ZMIZ1 in these samples via immunochemistry. Glucose uptake was analyzed through immunofluorescence and glucose uptake assay. We evaluated mRNA levels using qPCR and used plasmids transfection to knock down ZMIZ1 in PIG1 and PIG3V cell lines. The activation of the mTOR/AKT/GSK-3β signalling pathway was assessed using Western blotting analysis. We found that ZMIZ1 expression was decreased in VIT samples. Decreased ZMIZ1 expression inhibits the proliferation, migration, and invasion of melanocytes in vitro. Moreover, we revealed that decreased ZMIZ1 could also inhibit the glucose uptake of melanocytes in vitro. Decreased ZMIZ1 expression inhibits the activation of the mTOR/AKT/GSK-3β pathway and the expression of melanin synthesis-related proteins in melanocytes. Finally, we demonstrated that decreased ZMIZ1 may inhibit the cell viability of melanocytes and the synthesis of melanin by mTOR/AKT/GSK-3β-mediated oxidative stress in vitro. In conclusion, our study suggests that decreased ZMIZ1 suppresses melanogenesis in vitiligo by regulating the mTOR/AKT/GSK-3β-mediated glucose uptake in vitro, making ZMIZ1 an attractive therapeutic target for the treatment of VIT.

Incorporation of hair follicles in 3D bioprinted models of human skin.

Current approaches fail to adequately introduce complex adnexal structures such as hair follicles within tissue engineered models of skin. Here, we report on the use of 3D bioprinting to incorporate these structures in engineered skin tissues. Spheroids, induced by printing dermal papilla cells (DPCs) and human umbilical vein cells (HUVECs), were precisely printed within a pregelled dermal layer containing fibroblasts. The resulting tissue developed hair follicle-like structures upon maturation, supported by migration of keratinocytes and melanocytes, and their morphology and composition grossly mimicked that of the native skin tissue. Reconstructed skin models with increased complexity that better mimic native adnexal structures can have a substantial impact on regenerative medicine as grafts and efficacy models to test the safety of chemical compounds.

Loss of Dicer in Newborn Melanocytes Leads to Premature Hair Graying and Changes in Integrin Expression

Premature hair graying occurs owing to the depletion of melanocyte stem cells in the hair follicle, which can be accelerated by stress caused by genetic or environmental factors. However, the connection between stress and melanocyte stem cell loss is not fully understood. MicroRNAs are molecules that control gene expression by regulating mRNA stability and translation and are produced by the enzyme Dicer, which is repressed under stress. In this study, using 2 mouse genetic models and human and mouse cell lines, we found that the inactivation of Dicer in melanocytes leads to misplacement of these cells within the hair follicle, resulting in a lack of melanin transfer to keratinocytes in the growing hair and the exhaustion of the melanocyte stem cell pool. We also show that miR-92b, which regulates ItgaV mRNA and protein levels, plays a role in altering melanocyte migration. Overall, our findings suggest that the Dicer-miR92b-ItgaV pathway serves as a major signaling pathway linking stress to premature hair greying.

Two Novel Variants in MITF and PAX3 Associated With Splashed White Phenotypes in Horses.

Mutations causing depigmentation are relatively common in Equus caballus (horse). Over 40 alleles in multiple genes are associated with increased white spotting (as of February 2023). The splashed white phenotype, a coat spotting pattern described as appearing like the horse has been splashed with white paint, was previously associated with variants in the PAX3 and MITF genes. Both genes encode transcription factors known to control melanocyte migration and pigmentation. We report two novel mutations, a stop-gain mutation in PAX3 (XM_005610643.3:c.927C>T, ECA6:11,196,181, EquCab3.0) and a missense mutation in a binding domain of MITF (NM_001163874.1:c.993A>T, ECA16:21,559,940, EquCab3.0), each with a strong association with increased depigmentation in Pura Raza Española horses (P=1.144E-11, N=30, P=4.441E-16, N=39 respectively). Using a quantitative method to score depigmentation, the PAX3 and MITF mutations were found to have average white scores of 25.50 and 24.45, respectively, compared to the average white coat spotting score of 1.89 in the control set. The functional impact for each mutation was predicted to be moderate to extreme (I-TASSER, SMART, Variant Effect Predictor, SIFT). We propose to designate the MITF mutant allele as Splashed White 9 and the PAX3 mutant allele as Splashed White 10 per convention.

Uncovering genes underlying coat color variation in indigenous cattle breeds through genome-wide positive selection

The identification of candidate genes related to pigmentation and under selective sweep provides insights into the genetic basis of pigmentation and the evolutionary forces that have shaped this variation. The selective sweep events in the genes responsible for normal coat color in Indian cattle groups are still unknown. To find coat color genes displaying signs of selective sweeps in the indigenous cattle, we compiled a list of candidate genes previously investigated for their association with coat color and pigmentation. After that, we performed a genome-wide scan of positive selection signatures using the BovineSNP50K Bead Chip in 187 individuals of seven indigenous breeds. We applied a wide range of methods to find evidence of selection, such as Tajima’s D, CLR, iHS, varLD, ROH, and FST. We found a total of sixteen genes under selective sweep, that were involved in coat color and pigmentation physiology. These genes are CRIM1 in Gir, MC1R in Sahiwal, MYO5A, PMEL and POMC in Tharparkar, TYRP1, ERBB2, and ASIP in Red Sindhi, MITF, LOC789175, PAX3 and TYR in Ongole, and IRF2, SDR165 and, KIT in Nelore, ADAMTS19 in Hariana. These genes are related to melanin synthesis, the biology of melanocytes and melanosomes, and the migration and survival of melanocytes during development.

Postnatal Expression of Kitl Affects Pigmentation of the Epidermis

KITL signaling is important for melanocyte development in mammals; however, its function in the melanocyte stem cells in adult skin is not well-understood. In this study, we have generated genetically modified mice that express a Kitl transgene under the control of a doxycycline-inducible promoter to investigate the impact of its overexpression in embryo, young postnatal, and adult skin with intact hair follicles. We report that overexpression of KITL influences the proliferation and differentiation of melanocytes as well as the self-renewal capacity of resident melanocyte stem cells within the follicular niche. Notably, activation of Kit-KITL signaling induced the migration of melanocytes from hair follicles to the epidermis. In addition, we demonstrate that a single pulse of Kitl transgene expression in postnatal mice results in long-lasting effects on melanocyte stem cells and their differentiated progeny as pigmented skin cells that persist through adulthood. Our findings indicate that regulation of KITL signaling in melanocyte lineage is crucial for melanocyte stem cell homeostasis and melanocyte cell differentiation in postnatal and adult mice.

Differential expression of extracellular matrix proteins in the lesional skin of vitiligo patients.

Skin pigmentation is regulated by intricate interaction of the dermis and epidermis. The extracellular components present in the dermis play a very important role in the maintenance of skin homeostasis. Therefore, our objective was to check the expression of various ECM components secreted by the dermal fibroblasts in the lesional skin and non-lesional skin of vitiligo patients. For this study, skin punch biopsies (4mm) were collected from lesional skin (n = 12), non-lesional skin (n = 6) of non-segmental vitiligo patient's (NSV) and healthy control skin (n = 10). Masson's trichrome staining was performed to check the collagen fibre. The expression of collagen type 1, IV, elastin, fibronectin, E-cadherin and integrin β1 was checked by real-time PCR and immunohistochemistry. In this study, we demonstrated an increased expression of collagen type 1 in the lesional skin of vitiligo patients. The expression of collagen type IV, fibronectin, elastin and adhesion components such as E-cadherin and integrin β1 was observed to be significantly decreased in the lesional skin of NSV patients as compared to healthy control, whereas insignificant difference was observed between non-lesional and control skin. Increased expression of collagen type 1 in the lesional skin of vitiligo patients might be inhibiting the migration of melanocytes, whereas the decreased expression of elastin, collagen type IV, fibronectin, E-cadherins and integrins in the lesional skin may inhibit adhesion, migration, growth and differentiation of cells.

Stimulatory effects of Lycium shawii on human melanocyte proliferation, migration, and melanogenesis: In vitro and in silico studies.

There is no first-line treatment for vitiligo, a skin disease characterized by a lack of melanin produced by the melanocytes, resulting in an urgent demand for new therapeutic drugs capable of stimulating melanocyte functions, including melanogenesis. In this study, traditional medicinal plant extracts were tested for cultured human melanocyte proliferation, migration, and melanogenesis using MTT, scratch wound-healing assays, transmission electron microscopy, immunofluorescence staining, and Western blot technology. Of the methanolic extracts, Lycium shawii L. (L. shawii) extract increased melanocyte proliferation at low concentrations and modulated melanocyte migration. At the lowest tested concentration (i.e., 7.8μg/mL), the L. shawii methanolic extract promoted melanosome formation, maturation, and enhanced melanin production, which was associated with the upregulation of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1 and TRP-2 melanogenesis-related proteins, and melanogenesis-related proteins. After the chemical analysis and L. shawii extract-derived metabolite identification, the in silico studies revealed the molecular interactions between Metabolite 5, identified as apigenin (4,5,6-trihydroxyflavone), and the copper active site of tyrosinase, predicting enhanced tyrosinase activity and subsequent melanin formation. In conclusion, L. shawii methanolic extract stimulates melanocyte functions, including melanin production, and its derivative Metabolite 5 enhances tyrosinase activity, suggesting further investigation of the L. shawii extract-derived Metabolite 5 as a potential natural drug for vitiligo treatment.