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Background: Trichoscopy findings can differ in the skin of color requiring a dedicated approach with adequate examination in order to ensure proper diagnosis and treatment. This case series details three cases of concurrent lichen planopilaris (LPP) and female androgenic alopecia (FAGA) in the skin of color., Methods: Gross examination of all cases revealed mild to moderate hair density thinning of the temporal and frontal scalp. Trichoscopy was done in all three cases before biopsy. The temporal scalp of each patient showed diffuse hair follicle miniaturization with minimal terminal hairs and brown follicular halos, all findings were consistent with FAGA. However, upon inspection of the frontal scalp, each case revealed findings associated with scarring alopecia including scale, erythema, and peripilar casts in addition to the presence of follicle miniaturization., Results: In the first two cases, two punch biopsies were taken, one from the temporal scalp and one from the frontal scalp. Temporal biopsy revealed FAGA and frontal biopsy revealed LPP arising in a background of AGA. In the third case, only the frontal scalp was biopsied, which showed LPP in a background of FAGA. All three cases received the same treatment regimen; clobetasol 0.05% solution and minoxidil 5% foam/solution topically for treatment of FAGA and monthly intralesional triamcinolone acetonide for treatment of the LPP., Conclusion: Our report suggests the importance of total scalp dermoscopy and the need for biopsies in areas with varying dermoscopy findings as opposed to areas with the most significant hair loss. J Drugs Dermatol. 2025;24(3):320-322. doi:10.36849/JDD.7318.

Niacinamide, a derivative of vitamin B3, has been shown to reduce skin pigmentation (i.e., acting as a brightening agent) and inflammatory responses such as dermatitis and acne vulgaris. However, niacinamide is a hydrophilic compound and poor partitioning to the lipid matrix in the uppermost layer of the skin (the stratum corneum or SC) limits its delivery to the skin. This necessitates the use of penetration enhancers to increase its bio-availability. In this study, we used computer simulations to investigate the skin penetration of niacinamide alone and in combination with other brightening agents that are also shown to be skin penetration enhancers, namely undecylenoyl phenylalanine (Sepiwhite ® ), bisabolol, or sucrose dilaurate. Molecular dynamics simulations were performed to reveal molecular interactions of these brightening agents with a lipid bilayer model that mimics the SC lipid matrix. We observed minimal penetration of niacinamide into the SC lipid bilayer when applied alone or in combination with any one of the three compounds. However, when all three compounds were combined, a notable increase in penetration was observed. We showed a 32% increase in the niacinamide diffusivity in the presence of three other brightening agents, which also work as penetration enhancers for niacinamide. These findings suggest that formulations containing multiple brightening agents, which work as penetration enhancers, may improve skin penetration of niacinamide and enhance the effectiveness of the treatment.

Introduction: Vitiligo, an autoimmune disorder marked by skin depigmentation, is closely linked to immune dysregulation, including T cell infiltration and pro-inflammatory cytokines. This study explores the potential of baricitinib, a JAK-STAT inhibitor, in promoting repigmentation in vitiligo lesions by modulating immune responses., Methods: Using a mouse model of vitiligo induced by hydroquinone, we assessed the effects of baricitinib treatment on lesion repigmentation, CD8  +  T cell infiltration, T cell populations, and serum TNF-α levels. Immunostaining, flow cytometry, and ELISA were used to analyse these parameters., Results: Baricitinib treatment significantly reduced CD8  +  T cell infiltration in the skin, lowered serum TNF-α levels, and decreased both CD4  +  and CD8  +  T cell populations in the blood. Remarkably, these immune modulations correlated with notable repigmentation of the lesions., Conclusion: Baricitinib effectively reduces inflammation and T cell infiltration, suggesting it as a promising therapeutic for vitiligo. These findings highlight its potential to modulate immune responses and restore skin pigmentation in vitiligo patients., Competing Interests: Declarations. Conflit of interest: The authors declare no conflict of interest. Ethical approval: The study was approved by Institutional Animal Ethics Committee (PU/45/99/CPCSEA/IAEC/2020/423). The experimental protocols were carried out in accordance with the regulations set by Committee for Control and Supervision of Experiments on Animals for the Purpose of Scientific Research (CCSEA)., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Skin hyperpigmentation is a dermatological concern for pigmented skin phototypes. Despite availability of multiple treatment options, hyperpigmentation management continues to be a challenge., Aims: Efficacy and safety assessment of the skincare regimen [topical formulation of trihydroxybenzoic acid glucoside 10% (THBG) and α-arbutin 2% (twice-daily) + sunscreen (once daily)] in Indian females with pigmentary spots (facial dark spots or melasma)., Methods: This prospective, open-label, single-arm, interventional study was conducted in Indian females (n = 124), aged 18-45 years, having FitzPatrick skin type III-IV, dull skin, and facial dark spots or melasma. Efficacy of 90-day skincare regimen was evaluated using mexameter, modified melasma area and severity index (mMASI) score, cross-polarized light photography, chromameter, and color-luminosity-brightness-transparency (CLBT) technique. Student's t-test (paired data) was used for statistical analysis., Results: In efficacy analysis [modified intention-to-treat (mITT) population], 120 subjects were included. Melanin content of pigmentary spots (on mexametry) significantly reduced (-16.3%, p < 0.001) at Day 90 versus baseline. Significant reduction in severity of melasma was observed (-18.4% in mMASI score) at Day 90. Significant improvement in ΔEab (-8.7%) (change in color difference between pigmentary spot and normal skin) on cross-polarized photographs, in skin-brightening parameters L* (relative brightness/lightness) (-2.7%), ITA° (individual typology angle) (-37.7%), and ΔE* (skin-tone evenness) (-19.0%) using chromameter. Significant improvement in skin radiance was observed in CLBT parameters, color (pink: 32.8%, yellow: -5.5%, and olive: -7.8%), luminosity (6.0%), brightness (4.6%), and transparency (0.2%). Regimen did not cause itching, burning, or irritation., Conclusions: Skincare regime of 10% THBG and 2% α-arbutin along with sunscreen was effective in reducing pigmentary spots (dark spots and melasma) and was well tolerated in Indian women., Trial Registration: Clinical Trial Registry of India (CTRI Reg. No. CTRI/2021/11/038345; date: 30/11/2021)., (© 2025 Sun Pharma Laboratories Limited. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Introduction: With the growing demand for skin-enhancing products in the market, research into edible plants has expanded significantly. Numerous studies have shown that plant extracts rich in phytochemicals can effectively improve skin issues such as wrinkles, pigmentation, and dullness. However, clinical studies focusing on the effects of combined ingredients are still limited., Objective: This study combined three plant ingredients known for their skin-beautifying effects and clinically tested their functional properties., Methods: Sixty healthy subjects were screened and randomly divided into two groups: a test group (TG) and a placebo group (PG). TG took two tablets of multi-plant concentrated powder daily, while PG took placebo tablets without active ingredients. The study lasted 12 weeks. Plasma Trolox equivalent antioxidant capacity (TEAC), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were measured at week 0 (W0), week 8 (W8), and week 12 (W12). Skin brightness (L* value), skin tone (Individual Typological Angle (ITA°)), erythema (a* value), skin spots, and wrinkles were assessed at week 0 (W0), week 4 (W4), week 8 (W8), and week 12 (W12)., Results: The study showed significant improvements in all three antioxidant markers in the blood after consuming the compound ingredient tablets compared to the PG (p < 0.01). L* value and ITA° significantly increased from 8 weeks (p < 0.1). Skin spots significantly decreased at W8 and W12 (p < 0.1). While a* value and skin wrinkles showed noticeable reductions within the group in week 12 (p < 0.1), there were no significant differences compared to the PG., Conclusions: Consumption of multi-plant concentrated powder improved skin whitening, brightened skin tone, reduced skin spots, and showed some improvement in wrinkles and erythema., Trial Registration: ClinicalTrials.gov identifier: NCT05988567., (© 2025 Melaleuca Inc. TCI Co., Ltd and The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Post-inflammatory hyperpigmentation (PIHP) predominantly affects patients with melanin-rich skin, significantly impacting them psychosocially due to more frequent and severe pigmentary changes. In this study, the efficacy of a novel depigmenting agent 2-mercaptonicotinoyl glycine (Melasyl) in a dermocosmetic (DC) serum formulation is assessed as a stand-alone treatment of PIHP without sunscreen., Materials and Methods: Thirty-two Mauritian subjects aged 18-50 years of phototype IV-VI presenting mild acne (GEA2) and moderate to severe PIHP (PAHPI > 10) participated in this study. Subjects applied the DC serum twice a day on the whole face for 3 months. Efficacy was assessed through PAHPI score, mean darkness of lesions (0-8 scores), and colorimetric measurements at D0, D14, D28, D56, and D84. Self-perceived efficacy, tolerability, stigmatization, cosmeticity, and satisfaction were also gathered., Results: A significant decrease of 15.8% (p < 0.05) in PAHPI score was reported at D84. The PAHPI score showed marked changes (p < 0.05) in pigmentation intensity at D56. Visible significant changes in mean darkness were observed from D28, with a 25.1% decrease at D84. A significant brightening effect was observed in both the spots and adjacent areas, with their mean ITA values increasingly converging toward the ITA of the non-treated, non-exposed zone. This effect was more pronounced in the spots, which showed a significant increase from -34.1 to -14.2 by D14. Instrumental measurements revealed a 60% reduction in spot color intensity at D84 compared to the adjacent area Delta E (p < 0.05), significant from D14. Subjects reported self-perceived improvements in appearance and well-being that matched clinical results, enhancing their quality of life and satisfaction. The product was reported as very well tolerated by the subjects after 84 days of usage., Conclusion: This study demonstrated the efficacy and tolerability of the serum in the treatment of post acne PIHP. Good clinical results are confirmed by the objective measurement of the ITA and Delta E. Cosmeticity was excellent and will help observance in real life. The reduction of the stigmatization score illustrates the impact of PIHP and its improvement over time. These results can be considered highly encouraging with the new serum, as in real life, its use in combination with a UVA/visible light filtration sunscreen would probably increase patients benefit., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Introduction: Chronic actinic dermatitis (CAD) is an immunologically mediated photodermatosis that has been effectively treated with azathioprine and mycophenolate mofetil (MMF) in uncontrolled studies. We conducted a prospective randomized controlled trial to compare the efficacy and safety of azathioprine and MMF in CAD treatment, aiming to address existing evidence gaps., Materials and Methods: Consecutive CAD patients were randomized into two groups: azathioprine (Group A) or MMF (Group B) for 12 weeks. Primary outcomes included Eczema Area and Severity Index (EASI) and Dermatology Life Quality Index (DLQI) at baseline and Week 12. Secondary outcomes included various clinicodemographic factors predictive of treatment response, defined at least a 75% reduction in EASI score (EASI75) by Week 12., Results: The median (IQR) percentage reduction in EASI at 12 weeks was higher in Group B than in Group A [78.3% (75.0-83.30%) vs. 68.3% (31.2-80.10%), P = 0.034]. Baseline DLQI scores indicated a moderate impact on quality of life, with significant reductions by Week 12 in both groups and no intergroup differences at baseline (P = 0.291) or Week 12 (P = 0.599). Overall, 23 patients were classified as non-responders, with more extended illness duration (P = 0.026) and outdoor occupations (P = 0.042) associated with poorer responses. Adverse effects were consistent with known profiles, with one patient discontinuing azathioprine due to hypersensitivity., Conclusion: Our study highlights the efficacy and safety of azathioprine and MMF in CAD treatment, with MMF showing superior outcomes. However, further research is warranted to explore emerging therapies and prognostic factors in CAD management., (© 2024 the International Society of Dermatology.)

Background: Laser procedures are often used for global improvement in skin quality. The state of the skin is under stress after laser treatment, and it is beneficial to utilize topical agents to assist with optimal healing and cosmetic outcomes. Currently, such post-laser-cosmeceutical synergies are being investigated. Skin adaptogens are bioactive ingredients that enhance the skin's resistance and adaptation to stress., Aim: Investigate the use of an adaptogenic moisturizing serum (AMS) in synergy with post-laser treatment recovery., Patient/methods: Eight patients underwent long-pulsed 755-nm alexandrite or 1064-nm picosecond laser treatments on the face, targeting photoaging and pigmentation. After the laser treatment, during their healing process, they utilized a novel AMS twice daily to assist with the post-laser recovery. A blinded expert grader evaluated before and after facial images of each patient using a modified Griffiths photodamage photonumeric scale., Results: The findings revealed that the AMS was well-tolerated with no reported adverse events, and elicited aesthetically pleasing results. There was a significant decrease in photodamage scores following the treatment (p = 0.0078) with a median reduction of 3.5. Patients had improvement in skin photodamage, pigmentation, and skin radiance in clinic and photography after a combination of laser and AMS serum treatments., Conclusion: Utilizing the adaptogen moisturizing serum skin care regimen after the laser treatments likely assisted in the skin's healing process. As a result, we propose that there is a potential benefit of combining certain laser treatments and an adaptogen-based skin care regimen for better aesthetic outcomes and skin recuperation post-procedure., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Objective: Prosopis juliflora, commonly known as algaroba or mesquite, was introduced and has since proliferated throughout the semi-arid region of the Caatinga biome. Various studies have documented its properties, including antimicrobial, antioxidant, and antitumor activities, attributed to the presence of diverse secondary metabolites such as alkaloids, terpenoids, tannins, and flavonoids. The objective of this study was to evaluate the antioxidant and antityrosinase activities of P. juliflora fruit extract as a multifunctional active ingredient, and to develop cosmetic formulations containing this vegetal extract for potential applications in skincare products targeting pro-ageing and skin colour homogenization properties., Methods: The extraction process followed established protocols. Chemical characterization of the extract involved quantification of total flavonoids and phenolic compounds, along with Liquid Chromatography-Mass Spectrometry (LC-MS) analysis. In vitro antioxidant activity was assessed using different methods. Antityrosinase activity was determined by employing enzymatic assays. Cosmetic formulations containing Disodium EDTA, Phenoxyethanol (and) Ethylhexyl Glycerin, Distilled Water, Sodium Acrylates Copolymer Lecithin, Polyacrylamide (and) C13-14 Isoparaffin (and) Laureth-7, and 3.0% of the investigated plant extract were subjected to preliminary and accelerated stability tests., Results: The extract demonstrated a concentration of total flavonoids (1.71 ± 0.26 μg EQ/mg) and exhibited concentrations of phenolic compounds at 0.21 ± 0.01 mg EAG/g. Metabolites such as flavonoids and saponins were annotated, as well as some of their respective glycosidic derivatives. The extract showed antioxidant potential and the ability to inhibit the oxidation cascade in both the initiation and propagation phases. Moreover, the extract exhibited noteworthy inhibition of antityrosinase activity, presenting 62.48 ± 2.09 at a concentration of 30.00 mg/mL. The formulations were stable in accelerated stability tests over a 60-day period., Conclusion: This research not only demonstrates scientifically by demonstrating the potential of a plant from the Caatinga biome with antioxidant and antityrosinase properties in the development of cosmetic products aimed at pro-ageing effects and skin colour harmonization, but also adds value to the P. juliflora production chain. This valorization encompasses various aspects which include environmental, social, and biodiversity responsibilities., (© 2024 Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

The silkworm neuropeptide Orcokinin (abbreviated as BommoOK) is equipped with multiple biological functions, one of which acts as a pigmentation inhibitor. To explore the whitening efficiency of BommoOK, the inhibitory effects on tyrosinase and its adaptability on the cell for six mature peptides of BommoOK were investigated in this paper. At the same time, BommoOKA&#95;type4, the peptide with the best melanin inhibition effect, was used as an additive to prepare a whitening cream, and the effects on skin moisture, oil content, fine lines, skin glossiness, pores, and pigment depth were determined. The results revealed that the cream added with BommoOKA&#95;type4 peptide showed a good improvement effect on the skin, especially in significantly reducing the pigment depths of skin. The results displayed a potential application of BommoOK in whitening and skincare products as an excellent additive and provide certain references for the mechanism research of BommoOK in inhibiting melanin synthesis.

Both the surgical non-cultured melanocyte-keratinocyte transplant procedure (MKTP) and intradermal injection of 5-Fluorouracil (5-FU) are effective in the treatment of vitiligo. Intrablisters injection of MKTP was done in one study with better results than MKTP application after ablative CO2 laser of the reciepient area. However, intrablister injection of 5-FU was not done before. To compare the efficacy of 5-FU, MKTP after preparation of the recipient site by cryoblebing in the treatment of stable vitiligo. Treatment efficacy was evaluated clinically, histopathologically, and immunohistochemically. This prospective, single-blinded, randomized comparative study included 20 patients with stable vitiligo in 128 areas. The recipient sites were prepared by cryoblebbing. The blisters were injected with either a suspension of MKTP in area A (MKTP group, 49 areas), 5-FU in area B (5-FU group, 48 areas) or left without injection in area C (control group, 31 areas). The assessment was performed 6 months after the procedure based on the percentage of repigmentation, histopathologically and immunohistochemically for the pigmented lesions. Six months after treatment, the mean percentage change in repigmentation was 82.96% ± 31.46% in the MKTP group, 44.79% ± 39.38% in the 5-FU group, and 28.23% ± 24.00% in the control group.The median of the percent change was 100%, 37.5% and 25% in MKTP group, 5-FU group and control group, respectively, with a significant difference (P < 0.001) between the groups. After treatment, H&E-stained sections from the repigmented lesions showed the reappearance of melanocytes (MCs) and melanin pigmentation, especially in the MKTP group followed by 5-FU. Immunohistochemical staining revealed large MCs with an increased density of reactions and dendricity with positive expression of Melan A, and HMB45 especially in the MKTP and 5-FU groups. Intrablister injection with 5-FU appears to be effective for the management of stable vitiligo with less efficacy than MKTP., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The present study investigated the anti‑melanogenesis effects of Giant Centella asiatica (GCA), a new cultivator of Centella asiatica (CA) cataloged by the Korea Forest Service in 2022, and compared its efficacy with that of traditional CA. GCA has a high yield per unit area and enhanced antioxidant properties. The anti‑melanogenic effects of GCA were investigated using B16F10 melanoma cells and a 3D human skin‑equivalent model. Key molecular mechanisms were elucidated through western blotting, cAMP assays and molecular docking studies. Focus was addressed on the effect of GCA on skin whitening by comparing the ability of a GCA extract to inhibit melanin production in B16F10 melanoma cells and a 3D human skin‑equivalent model to that of CA. The results showed that the GCA extracts more effectively reduced melanin production, which was attributed to their higher content of two active components, madecassoside and asiaticoside. Further investigation revealed that GCA primarily inhibited melanogenesis through the PKA‑cAMP response element‑binding (CREB)‑microphthalmia‑associated transcription factor (MITF) axis, a key regulatory pathway in melanin synthesis. Notably, the present study, to the best of our knowledge, is the first to demonstrate that madecassoside and asiaticoside, the two principal compounds in GCA, directly bound to MC1R, which contributed to the significant skin‑whitening effects. Moreover, GCA reduced melanin production in a 3D human skin‑equivalent model, showing efficacy within a complex skin environment. These results demonstrated the superior effectiveness of GCA to that of CA for skin anti‑melanogenesis, indicating its potential as a promising natural material for targeting pigmentation disorders.

Although clofazimine is currently one of the standard regimens for Mycobacterium abscessus, it frequently causes skin discoloration, posing esthetic concerns for patients. We studied thirteen Asian patients with pulmonary nontuberculous mycobacterial disease treated with clofazimine at the NHO Kinki Chuo Chest Medical Center. In three patients (two women and one man) whose dosing regimens were altered owing to skin discoloration, we continuously measured luminance (L*), red-green (a*), and yellow-blue (b*) values (using a colorimeter) in both sun-exposed and sun-unexposed skin areas at each visit. Compared to baseline L* and a* values, the ΔL* values were negative (decreased brightness) and Δa* values were positive (increased redness) while patients received daily clofazimine. After switching to intermittent or reduced dosing, these changes gradually diminished. If such a dose reduction does not affect the therapeutic outcome, an even lower clofazimine dose may be attempted to minimize skin adverse effects., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Hyperpigmentation disorders are caused by the excess production and irregular accumulation of melanin. Existing treatments often have limited efficacy and adverse effects, necessitating the development of new skin-brightening agents. Lotus sprout extract (LSE) was identified as a potential pigment-correcting agent. However, the active compounds responsible for driving mechanisms related to this activity remain unknown., Aims: This study aimed to investigate the effects of LSE and its active components, neferine and liensinine, on melanin accumulation and to understand how LSE reduces skin pigmentation., Methods: Melanin accumulation was analyzed in MNT-1 human melanoma cells and MelanoDerm human skin equivalents following neferine, liensinine, or LSE treatment. The effects of the compounds on different pathways regulating melanin levels were evaluated by gene expression, biochemical assays, and western blotting. Melanosome ultrastructure was monitored using transmission electron microscopy (TEM)., Results: Neferine and liensinine reduced melanin accumulation in MNT-1 cells without downregulating melanogenesis-related genes or inhibiting tyrosinase activity. Instead, these compounds increased autophagic flux, suggesting that the reduction in pigmentation was due to increased melanin degradation. LSE also reduced melanin accumulation and activated autophagy in normal human melanocytes and MelanoDerm tissue. Autophagosomes induced by LSE treatment contained only melanosomes, and structural changes in melanosomes suggested that LSE may disrupt melanosome maturation., Conclusion: This study revealed a novel mechanism for LSE, neferine, and liensinine in reducing pigmentation, potentially through the induction of autophagy and subsequent melanosome degradation. These findings suggest that LSE and its enriched bioactive compounds could be promising agents for treating hyperpigmentation., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Circadian regulation of skin pigmentation is essential for thermoregulation, ultraviolet (UV) protection, and synchronization of skin cell renewal. This regulation involves both cell-autonomous photic responses and non-cell-autonomous hormonal control, particularly through melatonin produced in a light-sensitive manner. Photosensitive opsins, cryptochromes, and melatonin regulate circadian rhythms in skin pigment cells. We studied light/dark cycles and melatonin coordination in melanin synthesis and cell proliferation of Xenopus laevis melanophores. In vivo, tadpole pigmentation shows robust circadian regulation mainly hormone-driven, in that isolated melanophores respond strongly to melatonin but only slightly to light. Melanophore proliferation is faster in the dark and slower with melatonin as compared to a 12/12 light/dark cycle. Expression of circadian core genes (clock, bmal1, per1, per2, per3, cry1, cry2, and cry4) in melatonin-treated cells during the light phase mimics dark phase expression. Overexpression of individual Crys did not affect melanization or cell proliferation, likely due to their cooperative actions. Melanin synthesis was inhibited by circadian cycle deregulation through (a) pharmacological inhibition of Cry1 and Cry2 degradation with KL001, (b) continuous light or dark conditions, and (c) melatonin treatment. Our findings suggest that circadian cycle regulation, rather than proliferative capacity, alters melanization of melanophores., (© 2025 The Author(s). Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

Skin pigmentation is a widely recognized side effect of cancer chemotherapy that can negatively affect patient QOL. However, although numerous case reports have documented pigmentation caused by anticancer drugs, the precise mechanisms remain unclear. Among such pigmentation, that induced by 5-fluorouracil (5-FU) has garnered considerable attention, whereas reports on irinotecan-induced pigmentation are comparatively limited. In this study, we investigated the pigmentation-related effects of irinotecan in colored hairless mice. Mice received intraperitoneal injections of 20 mg/kg irinotecan, and we subsequently examined the pigmentation of the plantar and buttock regions. The results indicated that irinotecan specifically induces pigmentation in the plantar region, with no pigmentation observed on the buttocks. In contrast, pigmentation was noted on the buttocks, although not in the plantar region, in the control mice treated with 5-FU and cytarabine. Furthermore, irinotecan treatment promoted a marked elevation in the expression of tyrosinase, cAMP response element binding protein (CREB), and microphthalmia-associated transcription factor (MITF) in the plantar region, whereas no significant changes were observed in the buttocks. These findings indicate that irinotecan leads to site-specific pigmentation in the sole of the foot, thereby highlighting the potential for anticancer drugs to cause localized pigmentation.

Background: Conventional sunscreens shield the skin from ultraviolet (UV) rays up to 370 nm leaving wavelengths between 370 and 400 nm unfiltered despite their potentially harmful biological and clinical effects., Objective: The beneficial effects of methoxypropylamino cyclohexenylidene ethoxyethylcyanoacetate (MCE) UVA1 filter were explored at 1% in a SPF50 sunscreen under outdoors summer conditions against pigmentation and aging signs compared against a reference SPF50 without the MCE filter., Materials and Methods: A prospective randomized comparative intra-individual study was conducted in 52 Brazilian women (phototype I-III). A hemiface application was performed for the SPF50 sunscreen with 1% MCE and SPF50 reference without MCE before 1-h outdoor sunlight exposure, twice daily for 4 weeks. Study endpoint included expert panel grading of pigmentation (3), vascular (1) signs as well as facial skin ageing and assessment of facial skin radiance and skin homogeneity by a naïve panel., Results: Significant differences were reported for all facial signs comparing areas protected with SPF50/MCE and SPF50, respectively: upper lip wrinkles, crow's feet wrinkles, upper lip texture, upper lip pigmentation, vascular abnormalities (all p < 0.0001), texture of the mouth contour (p = 0.001), ptosis of lower face (p = 0.003), lateral facial pigmentation (p = 0.005), and whole face pigmentation (p = 0.01). The evaluations performed by naïve panel showed a significant superiority of the SPF50/MCE product for skin homogeneity (p = 0.043)., Conclusion: Overall, this study demonstrates a significant gain of protection with the SPF50 containing 1% MCE in reducing hyperpigmentation, redness and aging signs compared to the same SPF50 sunscreen without MCE, thus supporting the need for an enlarged UVA1 photoprotection., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Ectoine, a natural bacterial osmolyte, suppressed UVA irradiated-α-melanocyte stimulating hormone (MSH) stimulated melanogenesis through antioxidant Nrf2 pathways in human keratinocytes; however, the underlying skin whitening mechanisms were not elucidated. The depigmenting efficiency of Ectoine (0-400 μM) through antimelanogenesis and melanin degradation by autophagy promotion was investigated in melanoma (B16F10) and melanin-feeding keratinocyte (HaCaT) cells and in vivo zebrafish model. MTT assay, Western blotting, GFP-LC3 puncta, AVO formation, melanin assay, immunofluorescence staining, TEM techniques, siLC3 transfection, and zebrafish model were utilized. Ectoine-induced autophagy in B16F10 and HaCaT cells was shown by enhanced LC3-II accumulation, autophagosome GFP-LC3 puncta, autolysosome AVOs formation, ATG4B downregulation, and Beclin-1/Bcl-2 dysregulation. The immunoprecipitation data revealed that Ectoine increased the association between LC3-II and p62 proteins in B16F10 and HaCaT cells. Importantly, antioxidant NAC pretreatment antagonized the Ectoine-induced ATG4B diminution in B16F10 and HaCaT cells. Ectoine inhibited melanogenesis by suppressing melanosome gp100, tyrosinase, TRP-1/-2, and/or melanin formation via autophagy in α-MSH-stimulated B16F10 and melanin-feeding HaCaT cells. TEM findings displayed that Ectoine increased melanosome-engulfing autophagosomes and autolysosomes in α-MSH-stimulated B16F10 and melanin-feeding HaCaT cells. Ectoine-inhibited melanogenesis in α-MSH-stimulated B16F10 cells and melanin-feeding HaCaT cells was reversed by pretreatment with the autophagy inhibitor 3-MA or LC3 silencing. In vivo study demonstrated that Ectoine (5 mM) suppressed endogenous body pigmentation by antimelanogenesis and melanin degradation through autophagy induction in a zebrafish model. The in vitro and in vivo study demonstrated that Ectoine inhibits melanogenesis and enhances melanin degradation by triggering autophagy. Ectoine could be utilized as a whitening ingredient in cosmetic formulations., (© 2025 International Union of Biochemistry and Molecular Biology.)

Background: Halobacteria trueperi, an extremophilic microorganism thriving in high-salt environments, produces extracellular polysaccharides with potential anti-inflammatory and anti-aging properties. However, its clinical efficacy in skin improvement remains unclear. This study focuses on H. trueperi TCI66207, isolated from the Pacific Ocean at a depth of 662 m near Hualien, and its potential to enhance skin parameters, aiming to develop a novel functional formulation for pharmaceutical and cosmetic use., Aims: This sudy aims to evaluate the clinical efficacy of H. trueperi TCI66207 on various skin parameters and its potential for developing new functional cosmetic formulations., Patients/methods: A total of 40 subjects were recruited and randomly divided into two groups: the test group applied a serum containing H. trueperi TCI66207, while the placebo group used a basic serum. Subjects were instructed to apply the serum twice daily for 4 weeks. Skin parameters, including moisture, brightness, elasticity, pigmentation (spots and UV spots), texture, wrinkles, pores, and collagen density, were assessed before and after the 4-week application period., Results: After 4 weeks of using the H. trueperi TCI66207 serum, significant improvements were observed in all measured skin parameters compared to baseline, with notable enhancements in moisture, brightness, elasticity, texture, and collagen density, along with reductions in wrinkles, spots, and pore size., Conclusions: Halobacteria trueperi TCI66207 serum demonstrates a clear ability to improve skin conditions and delay signs of aging, making it a promising candidate for the development of new cosmetic formulations with potent anti-aging and skin-rejuvenating properties., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

The melanocortin-1 receptor (MC1R) is a G protein-coupled receptor that plays a pivotal role in human skin pigmentation, melanin synthesis, redox homeostasis and inflammation. Loss-of-function MC1R variants suppress G protein-coupled receptor coupling or cell surface expression leading to a decrease in adenyl cyclase activation and intracellular levels of cyclic adenosine monophosphate. Chronic activation of MC1R can occur in certain medical conditions such as Addison's disease and physiologic states such as pregnancy melasma. MC1R activation is more commonly caused by environmental exposure to ultraviolet (UV) radiation. Approved pharmacologic melanocortin agonists that activate MC1R signalling in a targeted manner or as a bystander effect have recently become available for erythropoietic protoporphyria, sexual desire disorders, monogenic obesity and syndromic obesity. Further, small peptide analogues of α-melanocortin-stimulating hormone, human MC1R selective agonists, are photoprotective, decreasing the adverse impact of UV radiation (a primary risk factor for skin cancer) and are being investigated as potential chemoprevention strategies. MC1R activation through induction of UV-protective skin pigmentation increased DNA repair, and control of aberrant cell growth may reduce the risk of melanoma but importantly does not prevent melanoma particularly in individuals with risk factors and regular skin examination remains critical in high-risk individuals., (© 2024 The Author(s). Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Vitiligo is the most frequently diagnosed depigmentation disease, affecting nearly 0.5-2% of individuals worldwide. This disorder is characterized by melanocyte loss, which results in skin and hair depigmentation. Psychological problems are common in patients, especially in those with the involvement of the face and hands. Several studies have recently focused on the use of JAK inhibitors for vitiligo treatment. However, studies on the selective JAK1 inhibitor upadacitinib for vitiligo treatment are limited. This study aimed to assess the efficacy and safety of upadacitinib in the treatment of vitiligo. This retrospective case series included five patients diagnosed with non-segmental vitiligo who were treated with upadacitinib for 4 months or longer. Disease severity was assessed using the Vitiligo Area Scoring Index (VASI). Five patients took 15 mg of upadacitinib orally for 4 consecutive months, and all achieved repigmentation. The plasma collected from the peripheral blood of the four patients showed that the CXCL9 level dropped after upadacitinib treatment. However, the CXCL10 level did not change significantly using enzyme-linked immunosorbent assay (ELISA). Flow cytometry revealed that the ratio of CD4 + CD3+/CD8 + CD3 + T cells in the blood samples tended to decrease through the treatment. And the Th1-like Tregs (CD4 + Foxp3 + IFN-γ + Tregs) were also downregulated in the peripheral blood. In conclusion, the JAK1 inhibitor upadacitinib was found to be effective and safe for treating non-segmental vitiligo., Competing Interests: Declarations. Ethics approval: Consent for the publication of recognizable patient photographs was obtained by the authors before the submission to the journal stating that all patients gave consent with the understanding that this information maybe publicly available. Approval for the use of the photos and peripheral blood samples was obtained from the Ethical Committee of the Hospital for Skin Disease, Institute of Dermatology, Chinese Academy of Medical Sciences, and Peking Union Medical College, and the ethics approval code is 2024-KY-043. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Little is known about the anti-pigmenting effects of skin-whitening agents on solar lentigos (SLs). To characterize the anti-pigmenting effects of a newly designed derivative ascorbyl glucoside-arginine complex (AGAC) on SLs, lotions with or without 28% AGAC were applied twice daily for 24 weeks in a double-blind half-face study of 27 Japanese females with SLs. The pigmentation scores and skin colors of previously selected SLs on the right and left sides of the faces of the subjects were evaluated using a photo-scale, a color difference meter and a Mexameter. Treatment with the test lotion elicited a significant decrease in pigmentation scores at 24 weeks compared to week 0, with a significant decrease in pigmentation scores at 24 weeks compared to the placebo lotion. In the test lotion-treated SLs, the lightness (L) and melanin index (MI) values that reflect the pigmentation level significantly increased and decreased, respectively, at 12 and 24 weeks of treatment compared to week 0. Comparisons of increased L values or decreased MI values between the test and placebo lotion-treated SLs demonstrated that the test lotion-treated SLs had significantly higher increased L or decreased MI values than the placebo lotion-treated SLs both at 12 and 24 weeks of treatment. The sum of our results strongly indicates that AGAC is distinctly effective in ameliorating the hyperpigmentation levels of SLs at a level visibly recognizable by the subjects, without any hypo-pigmenting effects or skin problems.

4-n-butylresorcinol (4-nBR) is a valuable ingredient to lighten skin and reduce pigmentation, contributing to an even skin tone and a more youthful appearance. However, its poor solubility, low stability, and strong irritation to the skin limit its application. In this study, 4-nBR was prepared into 4-n-butylresorcinol nanoemulsion (4-nBR-NE) for the first time, enhancing the solubility and stability of 4-nBR while greatly reducing its skin irritation. The relationship between the viscosity of nanoemulsion and the formulation process, as well as the impact of surfactant ratio on the formability of 4-nBR-NE were further studied. This led to the successful development of a nanoemulsion with adjustable viscosity (AV-NE) and with a low surfactant content. The particle size of 4-nBR-NE was 13.34 ± 0.16 nm with a PDI of 0.0853 ± 0.0191, indicating a uniform particle size distribution. The encapsulation rate of 4-nBR-NE was determined to be 80.05 ± 0.75 % via UV-Vis spectrophotometry. In addition, 4-nBR-NE demonstrated excellent stability over several months, with negligible changes in particle size. Cellular and transdermal evaluations confirmed that the preparation of 4-nBR-NE effectively reduced the original irritation cause by 4-nBR on cells and skin. Then, 4-nBR-NE was incorporated into an essence. This advancement enhances the applicability of 4-nBR in treating pigmentation disorders such as melasma and freckles, thereby increasing its applicability in pharmaceutical and cosmetic industries., Competing Interests: Declaration of Competing interest All authors disclosed no relevant relationships., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: Monobenzyl ether hydroquinone (MEBHQ) is a cream that promotes the spread and evenness of skin patches in vitiligo. Our aim was to investigate the oxidative and inflammatory effects of this cream on vitiligo patients consuming MEBHQ., Methods: A case-control study was conducted with three groups of 30 people from the control group, vitiligo patients before and after treatment. The percentage of vitiligo spots was determined by a specialist doctor. The levels of biochemical factors, oxidative stress profile and inflammatory factors were measured by enzymatic, colorimetric and ELISA methods, respectively., Results: Vitiligo patients showed a high level of inflammation and oxidative stress compared to healthy people. Although after 3 months of using MBEHQ cream, the percentage of skin spots in vitiligo patients increased from an average of 63%-91% and the skin color became almost uniform, but it still increased the level of oxidative stress and inflammation in these patients. Although the level of oxidative stress increased significantly in these patients, there was no significant increase in the level of malondialdehyde. The lack of significant differences in the levels of biochemical factors between healthy people and vitiligo patients before and after using the treatment shows the absence of side effects., Conclusion: The use of MBEHQ increased the size of skin spots and uneven skin color in vitiligo patients. Although MBEHQ did not show side effects such as diabetes, liver and kidney diseases, it increased the levels of oxidative stress and inflammatory cytokines, which needs further study., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: There is still no certain effective treatment for vitiligo as a common chronic skin disorder characterized by depigmented patches and loss of skin melanocytes., Objectives: This study evaluates the efficacy of oral silymarin combined with hair follicle transplantation compared to follicle transplantation alone in the treatment of refractory vitiligo., Materials and Methods: Twenty refractory vitiligo patients were enrolled in this randomized controlled clinical trial, following up for 3 months. One group underwent hair transplantation plus oral silymarin, while the other group underwent follicle transplantation alone. We assessed the progress with Vitiligo Extent Tensity Index (VETI) in both groups and the peri-follicular pigmentation diameter was estimated monthly. The Friedman test for comparing two groups at the end and the Mann-Whitney test for comparing two groups during each month was used., Results: The mean age was 30.22 (18-59) years, with the male to female ratio of 1:1. The decrease in the VETI and increase in the perifollicular pigmentation was statistically significant between silymarin and another group in monthly follow-up (p-value: 0.019, 0.019, and 0.035, respectively). Finally, the re-pigmentation was notable in silymarin group (p-value <0.001 vs. 0.029, respectively). In addition, both genders had a significant increase in peri-follicular re-pigmentation in the last follow-up (p-value: 0.012 and 0.044, respectively); although the improvement was not statistically significant between genders in each month., Conclusion: According to our study, silymarin in combination with hair transplantation could be a potential medical treatment for vitiligo; however, further trials are needed to establish the efficacy of combination therapies., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Phototoxic reactions are among the most common skin-related adverse effects induced by drugs. It is believed that the binding of chemicals to melanin biopolymers is a significant factor influencing skin toxicity. The formation of drug-melanin complexes can lead to the accumulation of drugs or their photodegradation products in pigmented cells, potentially affecting phototoxic reactions. Current procedures for assessing the phototoxic potential of drugs are based on tests using immortalized mouse fibroblasts. This study aimed to assess the phototoxic potential of selected drugs that form complexes with melanin (chloroquine, chlorpromazine, doxycycline) using human melanocytes with varying degrees of pigmentation. Parallel research was conducted on human dermal fibroblasts. To induce phototoxicity, cell cultures were irradiated using a sunlight simulator (5 J/cm 2 for UVA spectrum). To account for the process of drug accumulation, two experimental models with different incubation times of cells with drugs before irradiation were used. The photo-irritation factor (PIF) was calculated based on NRU and WST-1 screening tests. Additionally, cell viability was examined cytometrically, and analyses of the cell cycle and reduced glutathione levels were conducted. The results indicated that drugs binding with melanin exhibited different levels of cytotoxicity and phototoxicity towards fibroblasts and melanocytes. These observed differences impact the values of PIF, potentially complicating the interpretation of the studies. Additional analyses, such as examining cell subpopulations in the sub-G1 phase and determining the level of reduced glutathione, can enhance the assessment of the phototoxicity of drugs on pigmented cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The appearance of dull skin, uneven skin tone, dark spots, and hyperpigmentation is often bothersome, especially in individuals with darker skin tones. Management of skin dyschromia can be difficult. Several topical ingredients, such as niacinamide and vitamin C, are clinically proven to inhibit pigmentation formation and improve overall skin tone. A skincare regimen formulated to minimize irregular melanin deposition levels has been specifically developed to help improve uneven skin tone for a more radiant appearance. This regimen consists of an exfoliating cleanser (EC), an antioxidant C serum (ACS), a day cream with SPF (DC), and a renewing cream (RC)., Methods: A 12-week in-use clinical regimen study was conducted to assess the efficacy, tolerability, and consumer perception of these products on 43 subjects with mild-to-moderate uneven skin tone. Assessments included clinical photography, tolerability, and a self-assessment questionnaire., Results: There was a noticeable improvement in uneven skin tone, as shown in clinical photography across all timepoints (weeks 4, 8, and 12) compared to baseline. The regimen was safe and well tolerated for use and was highly acceptable among the subjects, with 81% of participants agreeing that their skin was more radiant since initiation of the regimen and 76% agreeing that the regimen had helped to significantly reduce the appearance of dark spots after 12 weeks of use. There were no reported adverse events., Conclusion: Overall, these data show that this regimen is effective in reducing the appearance of uneven skin tone. J Drugs Dermatol. 2024;23(12):1072-1075. doi:10.36849/JDD.8220.

Background and Aims: Solar lentigo is a prevalent skin condition that affects a significant number of individuals. Fortunately, certain traditional Chinese medicines and monomers (TCMM) have proven effective in addressing these concerns. In this study, we evaluated the efficacy and underlying mechanism of TCMM, a combination of TCM and monomers in repairing solar lentigo., Methods: We detected and identified the main compounds of TCM using liquid chromatography-mass spectrometry (LC-MS) and through the approach of network pharmacology, we screened drug and disease targets, visualized networks with Cytoscape software, analyzed targets via Gene ontology and KEGG, clinically validated predictions. In a mouse model, UVB-induced pigmentation was assessed, and the effects of TCMM were evaluated. A clinical trial on 30 patients validated the depigmenting agent., Results: Active ingredients such as MSH, Butylated hydroxytoluen, Valerophenone, and Geranylacetone aid pigmentation treatment. One hundred and forty-three crore targets impact PI3K-Akt, MAPK signaling pathway, ect. pathways. TCMM reduced UVB-induced pigmentation, water loss, epidermal thickness, and melanin. It inhibited TYR, MITF, AKT1, VEGFA, PTGS2, TNF-α, IL-6, IL-1β. Clinical and microscopic analysis showed significant pigmentation reduction., Conclusions: The treatment of solar lentigo can benefit from the TCMM. By targeting multiple factors and pathways, this approach offers a comprehensive and effective treatment strategy., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Melanin overexpression causes skin hyperpigmentation, which is associated with various skin disorders and cosmetic concerns. Umbelliferone, a natural coumarin found widely in plant species, has been noted for its antioxidant and anti-inflammatory effects but has received little attention for its impact on melanogenesis. Here, the effects of umbelliferone on melanogenesis were investigated in vitro and in clinical studies. The results showed that umbelliferone was non-cytotoxic to human skin and B16F10 melanoma cells. It also exhibited significant anti-melanogenic effects, reducing both melanin production and tyrosinase activity in a dose-dependent manner. This effect was achieved through a decrease in tyrosinase mRNA levels. Furthermore, umbelliferone in a formulation was stable under different temperature conditions, and after four weeks of topical application, it significantly decreased the melanin index and increased skin lightness (L*) values compared to those at the baseline. Overall, these findings demonstrate the potential of umbelliferone as a promising skin-lightening agent in the cosmetics industry.

(1) Background: Ultraviolet radiation takes part in photoaging and pigmentation disorders on skin. Epigallocatechin gallate (EGCG) is a well-known brightening and photoprotective compound but it faces limitations in terms of stability and solubility. (2) Methods: A more stable and water-soluble glucoside called EGCG-G1 was obtained by enzymatic glucosylation of EGCG. In vitro and ex vivo experiments evaluated EGCG-G1 skin penetration, antioxidant activity, and antimelanogenic properties compared to EGCG. This gene expression study characterized the pathways impacted by EGCG-G1. Four clinical studies covering phototypes I to V, at various ages, and different skin areas, using several tools, were conducted to assess the effect of EGCG-G1 on skin hyperpigmentation and tone. The impact of glucoside on skin microbiota, especially Lactobacillus sp., was assessed through in vitro and in vivo investigations. (3) Results: EGCG-G1 better penetrated the epidermis than EGCG due to a possible interaction with GLUT1. EGCG-G1 presented similar antioxidant activity to that of EGCG and decreased melanogenesis through the inhibition of 13 genes, including MITF. The skin Lactobacillus population increased with EGCG-G1, which promoted bacterial growth in vitro as prebiotic, and induced the release of a microbial brightening metabolite. Clinical trials demonstrated EGCG-G1 to decrease hyperpigmented spots and increase skin brightness and homogeneity in a large panel of phototypes, outperforming EGCG and vitamin C. (4) Conclusions: Glucosylation of EGCG maintained its photoprotective antioxidant properties and enhanced penetration across the epidermis. EGCG-G1 demonstrated brightening properties on all skin types by down-regulation of melanogenesis pathways and indirectly by skin microbiota stimulation.

Background: The treatment of vitiligo is a persistent challenge in dermatology. New treatments are being offered and studied in this field for those resistant to or intolerant of classical therapies., Aims: In this systematic review, we study the use of prostaglandin analogues (PGAs) and phosphodiesterase inhibitors (PDEIs) in the treatment of vitiligo, as they are known for their pigmentation inducing effects through activating melanocytes., Methods: We searched four main online databases with the keywords "Vitiligo", "Prostaglandin analogue" and "Phosphodiesterase inhibitor"., Results: A total of 42 articles were included, with 1027 cases, studying drugs like bimatoprost, latanoprost, travoprost, dinoprostone, apremilast, crisaborole, etc. Among the included studies, the treatment regimens are commonly once or twice daily for 12-48 weeks, with a mean of 20.61 weeks, and the routes of administration are mainly topical gels or ophthalmic solutions and oral tablets. Side effects are mild and tolerable, namely erythema, itching or burning sensations at application site for topicals, or gastrointestinal problems with apremilast. Repigmentation results are significant in both adult and pediatric patients and progressive or stable vitiligo. PGAs and PDEIs outperform many classical therapies, for example, narrowband ultraviolet B phototherapy (NB-UVB), tacrolimus, mometasone or methylprednisolone mini-pulse. PGAs or PDEIs are usually used in combination therapies to either cause synergism or increase drug delivery, and almost always enhance repigmentation, for example, with NB-UVB, fractional CO 2 laser, microneedling, and mometasone., Conclusion: Monotherapy or add-on PGAs and PDEIs can be considered effective treatments for vitiligo and promising last resorts for those resistant to other therapies., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Retinoids are derivatives of vitamin A prominently used in cosmeceuticals to reverse signs of photoaging. Retinaldehyde (retinal) is 10x more bioavailable than retinol and is gaining traction in the skincare industry for being the strongest over-the-counter retinoid. This study evaluated the efficacy and tolerability of a novel retinal formulation including peptides, ceramides, and lipids, designed to sustain the potency of the retinal and enhance delivery to reverse clinical signs of photoaging. This study was a trial of the test product (Retinal Night Advanced 0.1% Retinal Firming Treatment, Dr. Whitney Bowe Beauty, Greenwich, CT) in which 32 female subjects were enrolled. 47% of subjects had skin of color (Fitzpatrick Skin Type III-VI) and 57% had sensitive skin. Subjects applied the test product 3 nights weekly to the face, neck, and chest for 8 weeks. Fine lines of the face had 12% visible change by week 8 (P&lt;0.0001). Fine lines on the chest showed progressive visible improvement of 11% at week 2 (P=0.0005) and 19% at week 8 (P&lt;0.0001). There was a 19% improvement in visible hyperpigmentation of the face by the 8-week mark (P&lt;0.0001). Visible texture of the face improved by 5% (P=0.0078) and pores improved by 20% at week 8 (P&lt;0.0001). Patch testing revealed no signs of sensitization or irritation. This clinical study demonstrates that this retinal formulation is safe, well-tolerated, and effective in improving the appearance of fine lines, hyperpigmentation, texture, and pores. J Drugs Dermatol. 2024;23(11):992-997. doi:10.36849/JDD.8058R1&nbsp.

Skin cancer most commonly affects fair-skinned individuals1; however, it can appear in individuals of all skin tones. Photoprotective behaviors such as applying sunscreen should be practiced by all individuals regardless of skin tone. Herein, the authors discuss the cost and protection of popular sunscreens targeted towards patients with darker skin or skin of color (SOC), and suggest important considerations providers should take into account when advising about sunscreen recommendations for patients with skin of color. J Drugs Dermatol. 2024;23(11):e181-e182. doi:10.36849/JDD.8710e.

The potential therapeutic effects of carnosic acid (CA) on postinflammatory hyperpigmentation (PIH) were evaluated, including its effects on melanin deposition in zebrafish, melanogenesis and melanosome transfer in skin cells and skin wound healing in mice. Our results demonstrated that CA dose-dependently decreased melanin deposition in the skin of juvenile zebrafishes. It also inhibited melanogenesis in melanoma cells and melanosome transfer to keratinocytes. Next, CA was loaded in a liposome-hydrogel system (LP-GEL) to treat skin wounds in mice. The results showed that CA-LP-GEL, as well as LP-GEL, could accelerate skin wound healing and repair the structure of healing skins in mice. Comparatively, the levels of inflammatory factors (IL-1β and TNF-a) in healing skins were significantly increased by LP-GEL, but reduced by CA-LP-GEL. In addition, Fontana-Masson staining analysis of healing skin showed that the melanoma cells were restored by the treatment of LP-GEL and CA-LP-GEL, while the melanin content was significantly increased only by LP-GEL. Real-time PCR data showed that CA decreased the gene expression related with melanogenesis (MITF, TYR and TRP-1), melanosome transfer (MLPH, Myova and Rab27a) and inflammatory cytokines (IL-1β and TNF-α) in vitro and in vivo. In conclusion, CA could reduce melanin deposition in the skin by inhibiting melanogenesis and melanosome transfer. CA-LP-GEL was found to accelerate skin wound healing and suppress inflammation and hyperpigmentation in mice. These results suggest that CA has a big developing potentiality for PIH treatment., Competing Interests: Declaration of Competing Interest The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All authors read and approved the final manuscript., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Natural herbs have been widely considered a reservoir for skin-lightening ingredients, but discovery of the effective ingredients from herbs remains a large challenge., Aim: This research aimed to rapidly identify compounds with skin-lightening activity in Chinese herbs., Methods: The structure information of herbal compounds was collected and selected from the open-source data. High throughput virtual screening (HTVS) and Extra precision (XP) docking modes were used to screen for compounds that could bind to the mushroom tyrosinase involved in melanin synthesis. Furthermore, molecular dynamics (MD) simulations were introduced to assess the binding stability of those compounds with the key target protein. The candidate compounds found by this kind of multidimensional molecular screening were finally tested for their ability to inhibit pigmentation and potential toxicity using an in vivo zebrafish animal model., Results: A Natural Compounds Database was established with 5616 natural compounds. Fourteen compounds with favorable binding capability were screened by the XP docking mode with mushroom tyrosinase and five compounds among them were found to have superior dynamic binding performance through MD simulations. Then the Zebrafish animal experiments revealed that two components, sennoside B (SB) and sennoside C (SC), could significantly inhibit melanogenesis rather than the other three compounds. Meanwhile, there were no obvious side effects observed in SB and SC about the morphology, heart rate, or body length of zebrafish., Conclusion: A strategy for rapid screening of compounds with whitening activity has been established, and two potent skin-lightening compounds, SB and SC, have been identified from a vast library of herbal compounds. This study revealed that SB and SC have potential for topical use in skin lightening for the first time. The findings of this study would provide an important theoretical basis for the application of these two compounds in the cosmetic field in the future., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Poly-D,L-lactic acid (PDLLA) filler, which increases volume and collagen synthesis, is used for skin rejuvenation. PDLLA filler also increases M2 macrophages and IL-10. Ultraviolet (UV) radiation induces dermal hyperpigmentation by disrupting the basement membrane (BM), allowing melanin to move into the dermis. Therefore, using UV-irradiated macrophages and animal skin, we determined whether PDLLA filler decreased M1 macrophages and skin inflammation, thereby reducing BM destruction and dermal hyperpigmentation. UV radiation increased the M1 macrophage marker CD86 and TNF-α expression, which was inhibited by the treatment of macrophages with PDLLA. In fibroblasts treated with conditioned medium from UV-irradiated macrophages, NF-κB activity, NLRP3 inflammasome components (NLRP3, ASC, and pro-caspase-1), IL-18, MMP2, and MMP9 increased, but all decreased after PDLLA treatment. Similar to the in vitro study, UV-irradiated mouse skin showed increased CD86, NLRP3, ASC, pro-caspase-1, MMP2, and MMP9, which decreased after PDLLA injection. Disruption of the lamina densa of the BM and dermal pigmentation increased after UV irradiation and decreased after PDLLA injection. In conclusion, PDLLA reduced dermal pigmentation by decreasing BM destruction in UV-irradiated skin. PDLLA has the potential to reduce dermal pigmentation by regenerating the BM.

The oculocutaneous albinism II ( OCA2 ) gene encodes a melanosomal transmembrane protein involved in melanogenesis. Recent genome-wide association studies have identified several single nucleotide polymorphisms within OCA2 genes that are involved in skin pigmentation. Nevertheless, there have been no attempts to modulate this gene to improve skin discoloration. Accordingly, our aim was to identify compounds that can reduce OCA2 expression and to develop a formula that can improve skin brightness and reduce hyperpigmented spots. In this study, we investigated the effects of OCA2 expression reduction on melanin levels, melanosome pH, and autophagy induction through siRNA knockdown. Additionally, we identified several bioactives that effectively reduce OCA2 expression. Ultimately, in a clinical trial, we demonstrated that topical application of those compounds significantly improved skin tone and dark spots compared to vitamin C, a typical brightening agent. These findings demonstrate that OCA2 is a promising target for the development of efficacious cosmetics and therapeutics designed to treat hyperpigmentation.

Persistent racial disparities in health outcomes have catalyzed legislative reforms and heightened scientific focus recently. However, despite the well-documented properties of skin pigments in binding drug compounds, their impact on therapeutic efficacy and adverse drug responses remains insufficiently explored. This perspective examines the intricate relationships between variation in melanin-based skin pigmentation and pharmacokinetics and -dynamics, highlighting the need for considering diversity in skin pigmentation as a variable to advance the equitability of pharmacological interventions. The article provides guidelines on the selection of New Approach Methods (NAMs) to foster inclusive study designs in preclinical drug development pipelines, leading to an improved level of translatability to the clinic., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Tokishakuyakusan (TSS), a traditional Kampo medicine, can effectively alleviate symptoms unique to women, such as menstrual pain and menopausal symptoms, and this effect is believed to be related to its ability to increase the secretion of female hormones. TSS is also believed to be effective against skin pigmentation. However, no studies have examined the effect of TSS on pigmentation., Aim of the Study: In this study, we conducted basic research to determine the effects of TSS on pigmentation., Materials and Methods: Female HRM-2 mice were given free access to a normal diet or a TSS-containing diet for 7 weeks. For 3 weeks starting from the 4th week of treatment, the back of the skin was irradiated with ultraviolet (UV) light, and the melanin level was measured. The expression levels of melanogenesis-related genes and inflammatory markers in the skin were analyzed., Results: The melanin level in the skin of the mice exposed to UV radiation was approximately three times greater than that in the skin of the mice in the non-UV-irradiated group, confirming pigmentation due to UV irradiation. The protein expression levels of tyrosinase (Tyr), tyrosinase-related protein-1 (Tyrp1), and dopachrome tautomerase (Dct), which are important for melanin production, were significantly greater in the UV irradiation group than in the non-UV irradiation group. In contrast, the amount of skin melanin in the mice treated with TSS was significantly lower than that in the UV-irradiated group, and the expression levels of melanogenesis-related enzymes were also lower. Furthermore, TSS significantly decreased the expression of microphthalmia transcription factor (Mitf), a transcription factor for melanogenesis-related enzymes, and the inflammatory cytokines interleukin-1β and interleukin-6., Conclusions: TSS inhibits melanin production in melanocytes by suppressing the increase in the expression of melanogenesis-related enzymes caused by UV irradiation. These findings suggested that this effect of TSS is exerted through the combined regulation of MITF expression and anti-inflammatory responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Vitiligo remains a challenging condition to treat. Fire needle therapy, a traditional Chinese medicine technique, has potential as an alternative therapeutic strategy. However, rigorous evidence on its efficacy is lacking., Objective: We aimed to evaluate the efficacy and safety of fire needle therapy, alone and combined with topical tacrolimus ointment, for non-segmental stable vitiligo., Methods: In this 6-month randomized self-controlled trial, 35 vitiligo patients were enrolled, providing three similar lesions each. Lesions were randomly allocated to receive fire needle monotherapy, 0.1% tacrolimus ointment monotherapy, or combined fire needle and tacrolimus ointment therapy. The main outcome was change in vitiligo surface area., Results: In total, 29 patients completed the 6-month follow-up. The combination therapy group showed significantly greater reductions in vitiligo surface area compared to monotherapy groups starting at months 4 and 5. By the end of the study, combination therapy resulted in remarkably higher repigmentation responses, with 89.7% of lesions showing at least mild (≥25%) repigmentation and 51.7% showing good (≥50%) repigmentation. This significantly exceeded the outcomes with topical tacrolimus ointment alone, which only achieved 6.9% mild response and 6.9% good response. Fire needle monotherapy also demonstrated steady repigmentation over time, with 69% of lesions attaining a mild response by month 6. Importantly, no major adverse events occurred., Conclusion: This study provides promising preliminary evidence supporting the use of fire needle therapy, alone or in combination with topical tacrolimus ointment, for inducing repigmentation in non-segmental stable vitiligo. As a non-pharmacological approach, fire needle therapy warrants further study as an alternative vitiligo treatment., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

The oral administration of antioxidants may suppress UV-B-induced skin damage. HITHION YH-15, the extract of Torula yeast (Cyberlindnera jadinii), is rich in cysteine-containing peptides such as reduced and oxidized glutathione (GSH and GSSG), γ-glutamylcysteine (γ-Glu-Cys), and cysteinylglycine (Cys-Gly). These four constituents are termed cysteine peptides. In this study, we investigated the protective effects of cysteine peptides against UV-B in a randomized, placebo-controlled, double-blind, parallel-group study. A total of 90 healthy males and females aged 30-59 years were enrolled and randomized into two groups of 45 individuals each (cysteine peptides (48 mg/day) and placebo). Changes in UV-B-induced erythema and pigmentation were compared between groups after 5 weeks of test food intake. The minimal erythema dose (MED) significantly increased (*p = 0.019) in the cysteine peptides group compared to that in the placebo group, indicating suppression of UV-B-induced erythema. ΔL* value significantly increased (***p < 0.0001) in the cysteine peptides group compared to that in the placebo, indicating pigmentation suppression. We demonstrated that oral administration of cysteine peptides suppresses UV-B-induced erythema and pigmentation through multiple mechanisms. Thus, cysteine peptides may find use as nutricosmetics for maintaining skin health and well-being.UMIN Clinical Trials Registry ID: UMIN 000050157., (© 2024. The Author(s).)

Background: Photodynamic therapy (PDT) has been strongly recommended as an excellent alternative treatment for Bowen disease (BD). However, reported data on 5-aminolaevulinic acid-mediated PDT (ALA-PDT) with red-light irradiation are limited and the long-term effectiveness remains to be determined, especially in dark-skinned populations., Objectives: We aimed to review routine clinical practice in the field of BD treatment with ALA-PDT over an extended study period (2011-2021), calculate the overall clearance rate, and explore and evaluate factors that might affect the effectiveness of therapy in a real-world setting., Methods: The medical records of patients with BD who received ALA-PDT with red-light irradiation between February 2011 and June 2021 were reviewed and summarized. Univariate and multivariate analyses of clinically relevant variables that may affect treatment outcomes were conducted to identify risk predictors., Results: The overall clearance rate of 122 BD lesions was 89.3% with a median follow-up time of 36 months. The correlation between the effectiveness and fluorescence intensity of pre-PDT or PDT sessions was statistically significant after eliminating the interference of confounding factors. All recurrences occurred in the first 2 years following ALA-PDT., Conclusions: ALA-PDT is an effective treatment for BD in patients with darker-coloured skin. Well-executed operations and effective pretreatment are the determinants of effectiveness. Fluorescence intensity of pre-PDT appeared to be a significant predictor of final effectiveness. In addition, 2 years of follow-up is necessary following ALA-PDT., Competing Interests: Conflicts of interest The authors declare they have no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The primary function of the skin is to form a mechanical, permeability, antimicrobial, and ultraviolet radiation barrier, which is essential for maintaining physiological homeostasis. Our previous studies demonstrated that cutaneous pigmentation could promote skin barrier function in addition to providing anti-ultraviolet irradiation defense. The present study aimed to develop a new regimen that enhances skin barrier function by regulating skin pigmentation using low-concentration imiquimod. Results showed that topical application of low-concentration imiquimod effectively induced skin hyperpigmentation in the dorsal skin and external ear of mice without inducing inflammatory cell infiltration. An in vitro study also revealed that low-concentration imiquimod did not induce any cytotoxic effects on melanoma cells but triggered excessive melanin synthesis. In coculture systems, low-concentration imiquimod was noted to increase tyrosinase activity in a broader cellular context, revealing the potential role of neighboring cells in melanin production. The next-generation sequencing result indicated that PKCη and Dnm3 might regulate melanin synthesis and release during imiquimod treatment. Overall, our study presents new insights into the regulation of melanin production by low-concentration imiquimod, both in a mice model and cultured cells. Furthermore, our study highlights the potential benefits of imiquimod in promoting melanin synthesis without causing skin disruptions or inducing inflammation, validating its potential to serve as a method for enhancing skin barrier functions by regulating the epidermal melanization reaction., (© 2024 Wiley Periodicals LLC.)

The physiological role of α-melanocyte stimulating hormone in regulating integumental pigmentation of many vertebrate species has been recognized since the 1960's. However, its physiological significance for human pigmentation remained enigmatic until the 1990's. α-Melanocyte stimulating hormone and related melanocortins are synthesized locally in the skin, primarily by keratinocytes, in addition to the pituitary gland, and therefore act as paracrine factors for melanocytes. Human melanocytes express the melanocortin 1 receptor, which recognizes α-melanocyte stimulating hormone and the related adrenocorticotropic hormone as agonists. This review summarizes the current knowledge of the pleotropic effects of the activated melanocortin 1 receptor that maintain human melanocyte homeostasis by regulating melanogenesis and the response to environmental stressors, mainly solar radiation. Certain allelic variants of the melanocortin 1 receptor gene are associated with specific pigmentary phenotypes in various human populations. Variants associated with red hair phenotype compromise the function of the encoded receptor. Activation of the human melanocortin 1 receptor regulates eumelanin synthesis and enhances DNA damage response of melanocytes to solar radiation and oxidative stressors. We describe how synthetic selective melanocortin 1 receptor agonists can be efficacious as sunless tanning agents, for treatment of vitiligo and photosensitivity disorders, and for prevention of skin cancer, including melanoma., (© 2024 The Author(s). Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

Efficacy and safety of ritlecitinib (an oral JAK3/TEC family kinase inhibitor) were evaluated in patients with nonsegmental vitiligo (NSV) across Fitzpatrick skin types (FSTs). Patients with FST I-III ('light skin'; n = 247) and FST IV-VI ('dark skin'; n = 117) received once-daily ritlecitinib 50 mg (with/without 4-week loading dose), low-dose ritlecitinib or placebo for 24 weeks. At baseline, patients with light skin displayed higher CLM-1 and NCR1 serum levels than patients with dark skin (p < 0.05). At 24 weeks, ritlecitinib 50 mg improved the extent of depigmentation measured by percent change from baseline in facial-vitiligo area scoring index (placebo-adjusted mean difference [90% CI]) in patients with light (-15.2 [-24.7, -5.8]; p = 0.004) and dark (-37.4 [-50.3, -24.4]; p < 0.0001) skin, with continuous re-pigmentation through week 48. Treatment-emergent adverse events were similar across FSTs. At weeks 4 and 24, ritlecitinib 50 mg reduced CXCL11 serum levels (p < 0.001) in patients with light skin, whereas patients with dark skin had increased levels at week 4 (p = 0.05) and no significant change at week 24. Ritlecitinib 50 mg decreased IL-9 and IL-22 expression levels in dark skin compared with light skin (qPCR; p < 0.05). These differences in immune dysregulations may explain why NSV patients with dark skin respond to therapy earlier than patients with light skin., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Oral neomycin administration impacts the gut microbiome and delays vitiligo development in mice, and topical antibiotics may likewise allow the microbiome to preserve skin health and delay depigmentation. Here, we examined the effects of 6-week topical antibiotic treatment on vitiligo-prone pmel-1 mice. Bacitracin, Neosporin, or Vaseline were applied to one denuded flank, while the contralateral flank was treated with Vaseline in all mice. Ventral depigmentation was quantified weekly. We found that topical Neosporin treatment significantly reduced depigmentation and exhibited effects beyond the treated area, while Bacitracin ointment had no effect. Stool samples collected from four representative mice/group during treatment revealed that Neosporin treatment aligned with reduced abundance of the Alistipes genus in the gut, while relevant changes to the skin microbiome at end point were less apparent. Either antibiotic treatment led to reduced expression of MR1, potentially limiting mucosal-associated invariant T-cell activation, while Neosporin-treated skin selectively revealed significantly reduced CD8+ T-cell abundance. The latter finding aligned with reduced expression of multiple inflammatory markers and markedly increased regulatory T-cell density. Our studies on favorable skin and oral antibiotic treatment share the neomycin compound, and in either case, microbial changes were most apparent in stool samples. Taken together, neomycin-containing antibiotic applications can mediate skin Treg infiltration to limit vitiligo development. Our study highlights the therapeutic potential of short-term antibiotic applications to limit depigmentation vitiligo., (© 2024 The Authors. Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd.)

Acne can cause disfiguring sequelae, such as scarring, post-inflammatory erythema (PIE), and post-inflammatory hyperpigmentation (PIH). These post-inflammatory dyschromias pose a significant psychological burden on patients. This burden disproportionately affects skin of color (SOC) patients and can be the most distressing aspect of acne in SOC patients with skin types IV to VI. Multiple non-ablative lasers are used in the treatment of acne-related PIE and PIH. Combination therapies have shown promise in conditions such as rosacea, acne, and post-inflammatory dyschromia. Addressing both the inflammatory and scarring components of acne is key. Given the role of oxidation in the inflammatory cascade, including antioxidants could be an efficacious adjuvant with non-ablative lasers. This is a single-site, randomized, controlled clinical study of 25 subjects with skin types I to VI with facial PIE and/or PIH from acne. The primary objective was to investigate the clinical efficacy of non-ablative laser therapy followed by the topical application of Silymarin/Salicylic Acid/L-Ascorbic Acid/Ferulic Acid (SSAF) or control in the improvement in oily skin patients with facial PIE and PIH due to acne lesions. There was a statistically significant decrease in PIH and intralesional melanin in patients treated with a combination SSAF and non-ablative laser therapy. Improvement of both PIE and PIH was augmented in combination with SSAF and laser-treated patients compared with the laser-only group, with a concomitant increase in collagen density. This was even more strikingly marked in the SOC subjects, potentially providing an energy-based device (EBD)-based therapy in this population. Limitations of this study include small sample size and length of post-treatment follow-up. J Drugs Dermatol. 2024;23(9):769-773. doi:10.36849/JDD.8309.

Drug-induced pigmentation (DIP) is estimated to account for 20% of all cases of acquired hyperpigmentation. Over 50 agents have been implicated, including antibiotics, antimalarials, antiretrovirals, antipsychotics, prostaglandin analogs, heavy metals, and chemotherapeutic agents. The skin, mucosal surfaces, nails, and hair can all be affected, with the color, distribution, onset, and duration of pigmentation varying between offending agents. Both a thorough physical examination and medication history are necessary to determine the offending agent. In terms of mechanism, DIP occurs most frequently through the accumulation of melanin within the dermis but also by drug accumulation, pigment synthesis, and iron deposition. Photoprotection, including applying a broad-spectrum sunscreen, wearing photoprotective clothing, and seeking shade, plays an important role in the prevention of exacerbation of DIP. Multiple lasers, including the picosecond alexandrite, Q-switched Nd:YAG, Q-switched alexandrite, and Q-switched ruby lasers, have been successful in obtaining clearance of DIP. In this review, we examine the unique characteristics of each of the inciting agents in terms of incidence, clinical presentation, time to onset and resolution, and pathogenesis., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)