Reduced Melanin Synthesis Research Articles

Two-pore channel 2 is required for soluble adenylyl cyclase-dependent regulation of melanosomal pH and melanin synthesis.

Melanosomal pH is important for the synthesis of melanin as the rate-limiting enzyme, tyrosinase, is very pH-sensitive. The soluble adenylyl cyclase (sAC) signaling pathway was recently identified as a regulator of melanosomal pH in melanocytes; however, the melanosomal proteins critical for sAC-dependent regulation of melanosomal pH were undefined. We now systematically examine four well-characterized melanosomal membrane proteins to determine whether any of them are required for sAC-dependent regulation of melanosomal pH. We find that OA1, OCA2, and SLC45A2 are dispensable for sAC-dependent regulation of melanosomal pH. In contrast, TPC2 activity is required for sAC-dependent regulation of melanosomal pH and melanin synthesis. In addition, activation of TPC2 by NAADP-AM rescues melanosomal pH alkalinization and reduces melanin synthesis following pharmacologic or genetic inhibition of sAC signaling. These studies establish TPC2 as a critical melanosomal protein for sAC-dependent regulation of melanosomal pH and pigmentation.

Maclura cochinchinensis (Lour.) Corner Heartwood Extracts Containing Resveratrol and Oxyresveratrol Inhibit Melanogenesis in B16F10 Melanoma Cells.

This study aimed to isolate and purify resveratrol and oxyresveratrol from the heartwoods of Maclura cochinchinensis, and to evaluate their inhibitory effects on melanogenesis in B16F10 murine melanoma cells. A methanol maceration process yielded a crude extract comprising 24.86% of the initial mass, which was subsequently analyzed through HPTLC, HPLC, and LC-MS/MS. These analyses revealed the presence of resveratrol and oxyresveratrol at concentrations of 4.32 mg/g and 33.6 mg/g in the extract, respectively. Initial purification employing food-grade silica gel column chromatography separated the extract into two fractions: FA, exhibiting potent inhibition of both tyrosinase activity and melanogenesis, and FM, showing no such inhibitory activity. Further purification processes led to the isolation of fractions Y11 and Gn12 with enhanced concentrations of resveratrol (94.9 and 110.21 mg/g, respectively) and fractions Gn15 and Gn16 with elevated levels of oxyresveratrol (321.93 and 274.59 mg/g, respectively), all of which significantly reduced melanin synthesis. These outcomes affirm the substantial presence of resveratrol and oxyresveratrol in the heartwood of M. cochinchinensis, indicating their promising role as natural agents for skin lightening.

Potential Bioactivities of Tamarind Seed Jellose at the Cellular Level for Cosmetic Product Development

In recent years, the utilization of tamarind seeds as a potential and sustainable ingredient in green cosmetics has gained significant interest. These seeds, previously considered by-products in various food industries, are now being recognized for their interesting value and wide range of bioactive compounds. This study aimed to deeply examine the potential biological activities and underlying molecular mechanisms of tamarind seed jellose (TJ), a natural polysaccharide derived from Tamarindus indica seeds, for various cosmetic applications. Tyrosinase, a key regulator of melanin synthesis and skin color, was the main focus of this study. Through a series of in vitro experiments on skin fibroblasts and B16 melanoma cells, the cytotoxicity, antioxidant activity, and melanogenesis inhibitory potential of tamarind seed jellose were evaluated. Notably, the results revealed that TJ had no obvious cytotoxic effects on skin fibroblast cells at any tested concentrations, ranging from 0 to 10 mg/mL. Interestingly, tamarind seed jellose effectively reduced melanin synthesis by inhibiting tyrosinase expression in a dose-dependent manner. In addition, TJ exhibited a promising antioxidant activity. Collectively, these findings highlight that TJ has the potential to serve as a safe and multi-functional ingredient for green cosmetic applications, offering the potential opportunity to repurpose waste for the beauty industry.

Anti-melanogenic effect of Moju through inhibition of tyrosinase activity

BackgroundMoju is a traditional rice beverage local to Jeonju with an alcohol content of 1–2%. Moju is made by boiling makgeolli with several kinds of medicinal herbs, such as ginger, jujube and cinnamon. The raw materials used in Moju are well known for their physiological and functional effects. Although Moju is made with functional raw materials, the operational role of Moju has not yet been reported.ObjectivesThe aim of this study was to identify the anti-melanogenic effects of Moju in B16F10 melanoma cells and explore the potential mechanisms.ResultsIn this study, we investigated the antioxidant activity and anti-melanogenic effect of Moju. Moju showed no toxicity to HEK293T or B16F10 cells. The antioxidant activity of Moju was confirmed by its ability to increase radical scavenging activity. Moju decreased tyrosinase activity in a concentration-dependent manner. At the cellular level, Moju reduced melanin synthesis and the expression of proteins involved in melanin synthesis at concentrations of 100, 250, and 500 μg/mL in B16F10 cells. In addition, Moju inhibited the phosphorylation of extracellular signal-regulated kinase (ERK).ConclusionsThese results provide evidence that Moju has antioxidant activity and anti-melanogenic effect that occur through regulation of the ERK pathway. Although further research is needed to elucidate the specific mechanism and functional components, the ability of Moju to inhibit melanin synthesis by altering tyrosinase activation suggest that it can be used as a functional whitening ingredient.

Investigation of phenyllactic acid as a potent tyrosinase inhibitor produced by probiotics

Melanogenesis is responsible for skin pigmentation and the enzymatic browning of foods. Tyrosinases play a major role in melanin synthesis, and many attempts have been made to identify new natural tyrosinase inhibitors, but few have sought to do in microbes. Postbiotics are bioactive compounds produced by the metabolism of probiotics and have been reported to be safe and effective. In this study, we evaluated the tyrosinase inhibitory effects of culture supernatants of probiotics and discovered novel bacterial metabolites that can be used as a potent tyrosinase inhibitor based on metabolomics. Cultures of Bifidobacterium bifidum IDCC 4201 and Lactiplantibacillus plantarum IDCC 3501 showed effective anti-tyrosinase, reduced melanin synthesis, and altered protein expression associated with the melanogenesis pathway. Comparative metabolomics analyses conducted by GC-MS identified metabolites commonly produced by B. bifidum and L. plantarum. Of eight selected metabolites, phenyllactic acid exhibited significant tyrosinase-inhibitory activity. Our findings suggest that applications of probiotic culture supernatants containing high amounts of phenyllactic acid have potential use as anti-melanogenesis agents in food and medicines.

Prevalence of premature canities among college students studying in a private medical college, Chennai

Introduction: Canities is a scientific term used to describe the graying of hair. The graying of hair varies with age and ethnicity. Aging of hair occurs due to reduced melanin synthesis by the pigment producing cell melanocytes. Premature canities are becoming increasingly common. However, the etiology of premature canities remains unknown. Hence this study aimed to determine the prevalence of premature canities and its association with family history. Materials and methods: This cross-sectional study was conducted in the Department of Biochemistry of the students studying in ACS Medical College and Hospital from June 2018 to June 2019. Students aged less than 25 years participated in this present study. Results: Totally 519 volunteers 179 subjects had premature canities. The prevalence of Premature canities was 34.5%. It was more prevalent among females (n=97) 54% compared to males (n=82) 46%. Early onset of hair graying occurred in subjects with family history of gray hair. Among them 49 % of the subjects had family history of premature canities predominantly maternal family history (33%).

Lipopolysaccharide reduces melanin synthesis in vitiligo melanocytes by regulating autophagy.

Vitiligo is an autoimmune-related disease with a complex aetiology that involves innate immunity. Toll-like receptors (TLRs) are important parts of innate immunity and are related to a variety of autoimmune diseases, including vitiligo, through an unknown mechanism. In this study, we found that the TLR4 gene expression was increased in blood samples of patients with advanced stage vitiligo, and then, we evaluated the effect of TLR4 ligand lipopolysaccharide (LPS) on melanin synthesis in a vitiligo melanocyte cell line PIG3V and along with its mechanism. LPS suppressed melanin synthesis, downregulated the expression of melanin synthesis-related proteins and activated autophagy in vitiligo melanocytes. Inhibiting autophagy with 3-methyladenine or chloroquine blocked these effects. This suggests that LPS inhibits skin pigmentation by modulating autophagy, thus providing novel insights into the pathogenesis of vitiligo.

TRPA1 promotes melanosome phagocytosis in keratinocytes via PAR-2/CYLD axis

BackgroundKeratinocytes are recipients of melanosomes. Although the chemical basis of melanogenesis is well documented, the molecular mechanism of melanosome transfer must be elucidated. TRPA1 is a member of the transient receptor potential A subfamily. Previous studies have shown that inhibition of TRPA1 activity reduces melanin synthesis in human epidermal melanocytes; however, the mechanism remains unknown. ObjectiveThis study aimed to investigate the roles and mechanism(s) of action of TRPA1 in keratinocytes. MethodsThe correlation between TRPA1 expression levels and the ability of keratinocytes to phagocytize melanosomes was examined using melanin silver staining. TRPA1 depleted human epidermal keratinocytes and keratinocyte cell lines HaCaT were established using adenovirus-expressing shRNAs against TRPA1. The effects of TRPA1 on keratinocytes and HaCaT cells were determined using cell-based analyses, including light stimulation, calcium imaging, melanin phagocytosis, immunoblotting, and co-immunoprecipitation assays. The degree of epidermal pigmentation was determined in a guinea pig model. ResultsTRPA1 mediated the phagocytic activity of keratinocytes. TRPA1 knockdown markedly suppressed melanosome transport to keratinocytes. Mechanistically, TRPA1 was required for PAR-2-induced melanosome phagocytosis in keratinocytes. Furthermore, TRPA1 activation indirectly stabilized microtubules by promoting the competitive binding of CYLD and acetylated α-tubulin. In addition, bortezomib (PS-341), a proteasome inhibitor, increased TRPA1 and CYLD expression and promoted phagocytic activity both in vitro and in vivo. ConclusionsOur findings firstly suggest that TRPA1 promotes melanosome transport in keratinocytes and reveal that TRPA1 is a regulator of PAR-2 activation and microtubule stability via the PAR-2/CYLD axis.

Grape Extract Promoted α-MSH-Induced Melanogenesis in B16F10 Melanoma Cells, Which Was Inverse to Resveratrol.

Melanin is a natural pigment produced by cells to prevent damage caused by ultraviolet radiation. Previously, resveratrol was shown to reduce melanin synthesis. As a natural polyphenol with various biological activities, resveratrol occurs in a variety of beverages and plant foods, such as grapes. Therefore, we investigated whether grape extracts containing resveratrol also had the ability to regulate melanin synthesis. In this study, we used mouse B16F10 melanoma cells as a model for melanin synthesis with the melanogenesis-inducing α-melanocyte-stimulating hormone (α-MSH) as a positive control. Our results confirmed previous reports that resveratrol reduces melanin synthesis by reducing the activity of the rate-limiting enzyme tyrosinase. In contrast, the grape extract could not reduce melanin synthesis, and in fact promoted melanogenesis in the presence of α-MSH. The expression of genes related to melanin synthesis, such as tyrosinase, tyrosinase-related protein-1, tyrosinase-related protein-2, and microphthalmia-associated transcription factor, also supports these phenomena, which means that even in the presence of resveratrol, grape extract will strengthen the function of α-MSH in promoting melanin synthesis. Therefore, these results also provide a point of view for research on cosmetics.

Extracellular Vesicles from Korean Codium fragile and Sargassum fusiforme Negatively Regulate Melanin Synthesis.

Although various marine ingredients have been exploited for the development of cosmetic products, no previous study has examined the potential of seaweed extracellular vesicles (EV) in such applications. Our results revealed that EV from Codium fragile and Sargassum fusiforme effectively decreased α-MSH-mediated melanin synthesis in MNT-1 human melanoma cells, associated with downregulation of MITF (microphthalmia-associated transcription factor), tyrosinase and TRP1 (tyrosinase-related proteins 1). The most effective inhibitory concentrations of EV were 250 μg/ml for S. fusiforme and 25 μg/ml for C. fragile, without affecting the viability of MNT-1 cells. Both EV reduced melanin synthesis in the epidermal basal layer of a three-dimensional model of human epidermis. Moreover, the application of the prototype cream containing C. fragile EV (final 5 μg/ml) yielded 1.31% improvement in skin brightness in a clinical trial. Together, these results suggest that EV from C. fragile and S. fusiforme reduce melanin synthesis and may be potential therapeutic and/or supplementary whitening agents.

Ursodeoxycholic Acid May Inhibit Environmental Aging-Associated Hyperpigmentation.

Extrinsic aging of the skin caused by ultraviolet (UV) light or particulate matter is often manifested by hyperpigmentation due to increased melanogenesis in senescent skin. Ursodeoxycholic acid (UDCA), which has been commonly used as a health remedy for liver diseases, is known to possess antioxidant properties. This study was done to investigate whether UDCA inhibits cellular aging processes in the cells constituting human skin and it reduces melanin synthesis. ROS, intracellular signals, IL-1α, IL-8, TNF-α, cyclooxygenase (COX)-2, type I collagen, and matrix metalloproteinases (MMPs) levels were measured in human dermal fibroblasts treated with or without UDCA after UV exposure. Melanin levels and mechanistic pathways for melanogenesis were investigated. UDCA decreased ROS, senescence-associated secretory phenotype (SASP), and proinflammatory cytokines induced by UV treatment. UDCA reduced melanogenesis in normal human melanocytes cocultured with skin constituent cells. Our results suggest that UDCA could be a comprehensive agent for the treatment of environmental aging-associated hyperpigmentation disorders.

New Synthesized Galloyl‐RGD Inhibits Melanogenesis by Regulating the CREB and ERK Signaling Pathway in B16F10 Melanoma Cells

Gallic acid (3, 4, 5-trihydroxybenzoic acid) is a phytochemical derived from diverse herbs. It has been reported to have effective antifungal, antiviral and antioxidant activity. However, gallic acid exhibits low solubility and instability at high temperatures. In a previous study, in order to overcome these limitations, we synthesized galloyl-RGD by combining gallic acid with arginine, glycine and asparaginic acid (RGD peptide). This compound showed better thermal stability than gallic acid. In this study, we investigated the antimelanogenic effect of galloyl-RGD and the underlying mechanism for this effect. Galloyl-RGD markedly inhibited melanin content and tyrosinase activity in a concentration-dependent manner. We also found that galloyl-RGD decreased the levels of melanogenesis-related gene and protein. In addition, galloyl-RGD reduces intracellular cyclic adenosine monophosphate (cAMP) levels that leads to inhibition of cAMP-responsive element binding protein (CREB) phosphorylation and activates extracellular signal-regulated kinase (ERK) expression. These results indicate that CREB and ERK regulation by galloyl-RGD contributes to reduced melanin synthesis via degradation of microphthalmia-associated transcription factor. Therefore, galloyl-RGD can be potential candidate for application in cosmetic or pharmaceutical industry.

The Potential of Sulfated Polysaccharides Isolated from the Brown Seaweed Ecklonia maxima in Cosmetics: Antioxidant, Anti-melanogenesis, and Photoprotective Activities

Sulfated polysaccharides prepared from marine algae are potential ingredients in nutraceutical, pharmaceutical, and cosmeceutical industries. In the present study, the antioxidant, anti-melanogenesis, and photoprotective effects of sulfated polysaccharides obtained from Ecklonia maxima (EMC) were investigated to evaluate their potential in cosmetic. EMC was successfully prepared through Celluclast-assisted extraction and ethanol precipitation, and it contained 79.88% of sulfated polysaccharides that with 69.37% carbohydrates and 10.51% sulfate. EMC effectively suppressed 2,2-azobis(2-amidinopropane) hydrochloride (AAPH)-induced oxidative stress in vitro in Vero cells and in vivo in zebrafish. Furthermore, EMC significantly inhibited mushroom tyrosinase and reduced melanin synthesis in alpha-melanocyte-stimulating hormone-stimulated B16F10 cells. In addition, EMC remarkably attenuated photodamage induced by UVB irradiation in vitro in human keratinocytes (HaCaT cells) and in vivo in zebrafish. Furthermore, EMC effectively inhibited wrinkle-related enzymes and improved collagen synthesis in UVB-irradiated human dermal fibroblasts (HDF cells). These results indicate that EMC possesses strong antioxidant, anti-melanogenesis, and photoprotective activities, and suggest that EMC may be an ideal ingredient in the pharmaceutical and cosmeceutical industries.

Screening of an Epigenetic Drug Library Identifies 4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-Phenyl-Benzeneacetamide that Reduces Melanin Synthesis by Inhibiting Tyrosinase Activity Independently of Epigenetic Mechanisms.

The aim of this study was to identify novel antimelanogenic drugs from an epigenetic screening library containing various modulators targeting DNA methyltransferases, histone deacetylases, and other related enzymes/proteins. Of 141 drugs tested, K8 (4-((hydroxyamino)carbonyl)-N-(2-hydroxyethyl)-N-phenyl-benzeneacetamide; HPOB) was found to effectively inhibit the α-melanocyte-stimulating hormone (α-MSH)-induced melanin synthesis in B16-F10 murine melanoma cells without accompanying cytotoxicity. Additional experiments showed that K8 did not significantly reduce the mRNA and protein level of tyrosinase (TYR) or microphthalmia-associated transcription factor (MITF) in cells, but it potently inhibited the catalytic activity TYR in vitro (IC50, 1.1–1.5 µM) as compared to β-arbutin (IC50, 500–700 µM) or kojic acid (IC50, 63 µM). K8 showed copper chelating activity similar to kojic acid. Therefore, these data suggest that K8 inhibits cellular melanin synthesis not by downregulation of TYR protein expression through an epigenetic mechanism, but by direct inhibition of TYR catalytic activity through copper chelation. Metal chelating activity of K8 is not surprising because it is known to inhibit histone deacetylase (HDAC) 6 through zinc chelation. This study identified K8 as a potent inhibitor of cellular melanin synthesis, which may be useful for the treatment of hyperpigmentation disorders

Neobavaisoflavone Inhibits Melanogenesis through the Regulation of Akt/GSK-3β and MEK/ERK Pathways in B16F10 Cells and a Reconstructed Human 3D Skin Model.

Previous studies have confirmed the anti-melanogenic effect of the aerial part of Pueraria lobata, however, due to its inherent color, P. lobata has limited commercial use. In this study, an extract (GALM-DC) of the aerial part of P. lobata having improved color by the use of activated carbon was obtained. Furthermore, the active compound neobavaisoflavone (NBI) was identified from GALM-DC. The effect of NBI on melanogenesis, tyrosinase activity, α-glucosidase activity, and mechanism of action in melanocytes was investigated. Tyrosinase activity, melanin contents and the expression of melanin-related genes and proteins were determined in B16F10 cells. NBI reduced melanin synthesis and tyrosinase activity. Furthermore, NBI treatment reduced the mRNA and protein expression levels of MITF, TRP-1, and tyrosinase. NBI also works by phosphorylating and activating proteins that inhibit melanogenesis, such as GSK3β and ERK. Specific inhibitors of Akt/GSK-3β (LY294002) and MEK/ERK (PD98059) signaling prevented the inhibition of melanogenesis by NBI. NBI inhibited melanin production through the regulation of MEK/ERK and Akt/GSK-3β signaling pathways in α-MSH-stimulated B16F10 cells. NBI suppresses tyrosinase activity and melanogenesis through inhibition of α-glucosidase activity. Besides, NBI significantly reduced melanogenesis in a reconstructed human 3D skin model. In conclusion, these results suggest that NBI has potential as a skin-whitening agent for hyperpigmentation.

D-tyrosine adds an anti-melanogenic effect to cosmetic peptides

D-tyrosine is known to negatively regulate melanin synthesis by inhibiting tyrosinase activity. Here, we further reveal that peptides containing terminal D-tyrosine can reduce the melanin contents of human melanocytes. The addition of D-tyrosine to the terminus of the commercial anti-wrinkle peptide, pentapeptide-18 endowed the peptide with the ability to reduce the melanin content and tyrosinase activity in human MNT-1 melanoma cells and primary melanocytes. Consistently, terminal D-tyrosine-containing pentapeptide-18 inhibited the melanogenesis induced by α-MSH treatment or UV irradiation of MNT-1 cells and reduced melanin synthesis in the epidermal basal layer of a 3D human skin model. Furthermore, the addition of D-tyrosine to an anti-aging peptide (GEKG) or an anti-inflammatory peptide (GHK) endowed these short peptides with anti-melanogenic effects without altering their intrinsic effects. Together, these data suggest that the addition of D-tyrosine at the terminus of a short cosmetic peptide adds an anti-melanogenic effect to its intrinsic cosmetic effect. Our work offers a novel means of generating dual-function cosmetic peptides.

One-year pilot study on the effects of nitisinone on melanin in patients with OCA-1B

BACKGROUND. Oculocutaneous albinism (OCA) results in reduced melanin synthesis, skin hypopigmentation, increased risk of UV-induced malignancy, and developmental eye abnormalities affecting vision. No treatments exist. We have shown that oral nitisinone increases ocular and fur pigmentation in a mouse model of one form of albinism, OCA-1B, due to hypomorphic mutations in the Tyrosinase gene.METHODS. In this open-label pilot study, 5 adult patients with OCA-1B established baseline measurements of iris, skin, and hair pigmentation and were treated over 12 months with 2 mg/d oral nitisinone. Changes in pigmentation and visual function were evaluated at 3-month intervals.RESULTS. The mean change in iris transillumination, a marker of melanin, from baseline was 1.0 ± 1.54 points, representing no change. The method of iris transillumination grading showed a high intergrader reliability (intraclass correlation coefficient ≥ 0.88 at each visit). The number of letters read (visual acuity) improved significantly at month 12 for both eyes (right eye, OD, mean 4.2 [95% CI, 0.3, 8.1], P = 0.04) and left eye (OS, 5 [1.0, 9.1], P = 0.003). Skin pigmentation on the inner bicep increased (M index increase = 1.72 [0.03, 3.41], P = 0.047). Finally, hair pigmentation increased by both reflectometry (M index [17.3 {4.4, 30.2}, P = 0.01]) and biochemically.CONCLUSION. Nitisinone did not result in an increase in iris melanin content but may increase hair and skin pigmentation in patients with OCA-1B. The iris transillumination grading scale used in this study proved robust, with potential for use in future clinical trials.TRIAL REGISTRATION. ClinicalTrials.gov NCT01838655.FUNDING. Intramural program of the National Eye Institute.

The Anti-melanogenesis Activities of Some Selected Brown Macroalgae from Northern Coasts of the Persian Gulf

Abstract Melanogenesis is a biological process which led to the synthesis of melanin pigment. Abnormal melanin production results in melasma, solar lentigo, post inflammatory melanoderma, etc. In this study, we examined the potential inhibitory effects of 17 brown macroalgae from Persian Gulf on melanogenesis. The effects of various concentrations (100, 250 and 500 µg/mL) of methanolic extracts of macroalgae belonging to four genera (including: Padina, Colpomonia, Cystoseira and Sargassum) were studied on oxidation of L-Dopa by mushroom tyrosinase. Subsequently, the activity of macroalgae with high inhibitory effect on monophenolase activity of mushroom tyrosinase and zebrafish was investigated using L-tyrosine as a substrate. Anti-melanogenesis effects of algae extracts were studied on zebrafish as an alternative in vivo model. Kojic acid was used as a positive control. All the tested macroalgae showed inhibitory effect on activities of diphenolase and monophenolase (of mushroom tyrosinase). P. boergesinii exhibited the most in vivo anti-tyrosinase activity compared with other samples. P. boergesenii inhibited zebrafish tyrosinase more potent than kojic acid (83% vs 50% inhibition for kojic acid). Moreover, it reduced melanin synthesis in zebrafish 42% (kojic acid: 50%).

Pulsed Electromagnetic Fields Increase Pigmentation through the p-ERK/p-p38 Pathway in Zebrafish (Danio rerio).

Melanogenesis is a biological process resulting in the production of melanin pigment, which plays an important role in the prevention of sun-induced skin injury, and determines hair and skin color. So, a wide variety of approaches have been proposed to increase the synthesis of melanin. This study evaluated the effects of pulsed electromagnetic fields (PEMFs) on the pigmentation of zebrafish (Danio rerio) in vivo. We stimulated pigmentation in zebrafish by using specific frequencies and intensities of PEMFs. This study focuses on pigmentation using PEMFs, and finds that PEMFs, at an optimal intensity and frequency, upregulate pigmentation by the stimulated expression of tyrosinase-related protein 1 (TRP1), dopachrome tautomerase (DCT) through extracellular signal-regulated kinase(ERK) phosphorylation, and p38 phosphorylation signaling pathways in zebrafish. These results suggest that PEMFs, at an optimal intensity and frequency, are a useful tool in treating gray hair, with reduced melanin synthesis in the hair shaft or hypopigmentation-related skin disorders.

Thai herbal antipyretic 22 formula (APF22) inhibits UVA‐mediated melanogenesis through activation of Nrf2‐regulated antioxidant defense

Thai herbal antipyretic 22 formula (APF22), a polyherbal formula, has been traditionally used to treat dermatologic problems including hyperpigmentation. Exposure of the skin to ultraviolet A (UVA) causes abnormal melanin production induced by photooxidative stress. This study thus aimed to investigate the protective effects of APF22 extracts and phenolic compounds, ferulic acid (FA), and gallic acid (GA; used as positive control and reference compounds), on melanogenesis through modulation of nuclear factor E2-related factor 2 (Nrf2) signaling and antioxidant defenses in mouse melanoma (B16F10) cells exposed to UVA. Our results revealed that the APF22 extracts, FA, and GA reduced melanin synthesis as well as activity and protein levels of tyrosinase in UVA-irradiated B16F10 cells. Moreover, APF22 extracts and both FA and GA were able to activate Nrf2-antioxidant response element signaling and promote antioxidant defenses including glutathione, catalase, glutathione peroxidase, and the glutathione-S-transferase at both mRNA and enzyme activity levels in irradiated cells. In conclusion, APF22 extracts suppressed UVA-mediated melanogenesis in B16F10 cells possibly via redox mechanisms involving activation of Nrf2 signaling and upregulation of antioxidant defenses. Moreover, pharmacological action of the APF22 extracts may be attributed to the phenolic compounds, FA, and GA, probably serving as the APF22's active compounds.