Melanin Research Articles

Bay 11-7082, an NF-κB Inhibitor, Prevents Post-Inflammatory Hyperpigmentation Through Inhibition of Inflammation and Melanogenesis.

Post-inflammatory hyperpigmentation (PIH) is a very common disorder of cutaneous hyperpigmentation, which poses a persistent management challenge in the fields of dermatology and esthetics. This study was designed to explore the anti-melanogenic and anti-inflammatory effects of Bay 11-7082, an NF-κB inhibitor, using small-molecule screening, to determine its potential application for PIH prevention. The molecular mechanisms were investigated invitro and exvivo in epidermis-humanized mice using melanin content, RT-PCR, and immunoblotting. Bay 11-7082 suppressed proinflammatory cytokines and ameliorated 2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis on day 15. The suppression of melanin synthesis by Bay 11-7082 was attributed to the reduction of MITF, which was induced by extracellular signal-regulated kinase activation. Bay 11-7082 reduced epidermal melanin accumulation in UVB-stimulated exvivo human epidermis as well as in the ear and tail skin of K14-stem cell factor (SCF) transgenic mice. Topical administration of Bay 11-7082 improved PIH on day 35 in the post-DNFB dorsal skin of K14-SCF transgenic mice. In conclusion, Bay 11-7082 can be considered a promising candidate for the development of a preventive topical agent for PIH.

Study on the Differences in Fecal Metabolites and Microbial Diversity of Jiangshan Black-Bone Chickens with Different Earlobe Colors

The differences in earlobe color of Jiangshan black-bone chickens have been reported to be caused by the combined effects of melanin and collagen. In this study, we conducted LC-MS untargeted metabolomics and 16S rDNA diversity sequencing on the cecal contents of two types of earlobes: peacock green (Blue and Green group) and dark reddish-purple (Black group). The metabolomic sequencing identified a total of 747 differential metabolites (DMs), in which the metabolites were primarily enriched in tyrosine and tryptophan metabolism pathways between peacock green and dark reddish-purple earlobes. There were 15 different bacterial taxa among the three groups of earlobes at the genus level, and correlation analysis between metabolites and microbes revealed that the DMs between peacock green and dark reddish-purple earlobes were positively correlated with the different bacterial taxa. In short, there are differences in gut microbiota and metabolites between Jiangshan black-bone chickens with peacock green earlobes and those with dark reddish-purple earlobes. Our results suggest that the bacterial phyla Firmicutes and Bacteroidota may influence melanin synthesis by affecting tryptophan metabolism, induced by 5-Methoxyindoleacetate, and tyrosine metabolism, induced by maleylacetoacetic acid and maleic acid, leading to differences in earlobe color.

A Repurposing Pipeline to Candidate-Suitable Inhibitors of Tyrosinase: Computational and Bioassay Studies.

Tyrosinase, a metalloprotein enzyme, plays a crucial role in melanin synthesis by hydroxylating L-tyrosine to L-dopa. However, the accumulation of melanin can lead to hyperpigmented spots, raising aesthetic concerns. In this study, we developed a pipeline to repurpose FDA-approved drugs as potential tyrosinase inhibitors. A structure-based screening study was conducted using 1,650 drugs to identify probable inhibitors based on binding energies. From the cluster analysis of binding interaction profiles, 16 compounds were selected as candidates. Montelukast emerged as the final candidate due to its favorable ADME properties. Bioassay evaluation revealed an IC50 value of 14.79±0.87 μM for Montelukast, compared to kojic acid (IC50=31.02±2.01 μM). Molecular dynamics simulation and g_MMPBSA free energy calculation studies were performed for the Tyrosinase-Montelukast complex. These findings enhance our understanding of Tyrosinase-Montelukast interactions and underscore Montelukast's potential as a tyrosinase inhibitor. This could have implications in dermatological applications and beyond, suggesting Montelukast as a promising candidate for further development in this regard.

Unveiling New Horizons: Advancing Technologies in Cosmeceuticals for Anti-Aging Solutions

In the last years, the landscape of anti-aging cosmetics has been marked by significant advances in cosmeceutical delivery systems. This study aimed to conduct a systematic review of these technological innovations, with a focus on anti-aging effects, from 2018 to 2023. The methodology included a thorough search on PubMed and through gray literature, applying rigorous exclusion criteria. The descriptors were selected based on the Medical Subject Headings (MeSH). A total of 265 articles were found. Exclusion criteria were applied, and 90 of them were selected for full reading. After reading the full 90 articles, 52 were excluded, leaving 38 articles for final evaluation composing this review. The key findings highlighted a clear prevalence of studies exploring nanotechnology, including nanoparticles, niosomes, and liposomes. Most of the formulations analyzed in this review emphasize antioxidant activities, which play a crucial role in preventing premature aging caused by free radicals. The reviewed studies revealed specific activities, such as the reduction in melanin synthesis, the inhibition of enzymes involved in the skin aging process, and the prevention of morphological changes typical of aging.

A missense mutation in the tyrosinase gene explains acromelanism in domesticated canaries.

Acromelanism is a form of albinism observed in several vertebrate species. In mammals, acromelanism is known to be caused by mutations in the tyrosinase gene (TYR) that induce a temperature-sensitive behavior of melanin synthesis, resulting in a characteristic hair color gradient. In birds, several phenotypes consistent with acromelanism have been reported, but their genetic basis remains unknown. This study aimed to identify the genetic basis of an acromelanistic phenotype in domesticated canaries known as pearl and test whether it is caused by the same molecular mechanism described for mammals. To do this, we compared the genomes of pearl and non-pearl canaries and searched for potentially causative genetic mutations. Our results suggest that the pearl phenotype is caused by a mutation in the TYR gene encoding a TYR-P45H missense substitution. Our findings further suggest that reports of acromelanism in other bird species might be explained by TYR mutations.

Mapping epidermal and dermal cellular senescence in human skin aging.

Single-cell RNA sequencing and spatial transcriptomics enable unprecedented insight into cellular and molecular pathways implicated in human skin aging and regeneration. Senescent cells are individual cells that are irreversibly cell cycle arrested and can accumulate across the human lifespan due to cell-intrinsic and -extrinsic stressors. With an atlas of single-cell RNA-sequencing and spatial transcriptomics, epidermal and dermal senescence and its effects were investigated, with a focus on melanocytes and fibroblasts. Photoaging due to ultraviolet light exposure was associated with higher burdens of senescent cells, a sign of biological aging, compared to chronological aging. A skin-specific cellular senescence gene set, termed SenSkin™, was curated and confirmed to be elevated in the context of photoaging, chronological aging, and non-replicating CDKN1A+ (p21) cells. In the epidermis, senescent melanocytes were associated with elevated melanin synthesis, suggesting haphazard pigmentation, while in the dermis, senescent reticular dermal fibroblasts were associated with decreased collagen and elastic fiber synthesis. Spatial analysis revealed the tendency for senescent cells to cluster, particularly in photoaged skin. This work proposes a strategy for characterizing age-related skin dysfunction through the lens of cellular senescence and suggests a role for senescent epidermal cells (i.e., melanocytes) and senescent dermal cells (i.e., reticular dermal fibroblasts) in age-related skin sequelae.

TCONS_00025035-miR-101-UROS is potentially involved in the regulation of heme synthesis pathway and influences mantle melanin deposition by targeting porphyrin in Manila clam (Ruditapes philippinarum)

Shell color is an important economic trait and one of the target traits in breeding and production. Non-coding RNA (ncRNA) refers to RNA molecules transcribed from the genome and do not encoding proteins, which can regulate the expression of target genes after transcription and participate in the regulation of many important traits, such as the formation of shell color and body color. In this study, we detected the porphyrins in the shells of three Manila clams with different shell colors, explored the expression pattern and function of Uroporphyrinogen III synthetase (UROS) in the shell color pigmentation of Ruditapes philippinarum, and found that it might be involved in the synthesis of porphyrins and potentially in the synthesis of melanin. The results showed that the expression levels of heme synthesis-related genes such as UROS, Uroporphyrinogen decarboxylase (UROD), Ferrochelatase (FECH), Hephaestin (HEPH), and pigment synthesis-related genes (Peroxidasin PXDN) in the positive group were significantly reduced compared with the control group after injection of UROS dsRNA, indicating that UROS plays a crucial role in the porphyrin synthesis pathway. Additionally, transmission electron microscopy and melanin extraction experiments also proved that it might participate in the synthesis of melanin. We further explored and verified the relationship between TCONS_00025035-miR-101-UROS and identified the changes in the expression level of UROS through RNA interference and injection of miR-101 antagomir, respectively. Our results imply that miR-101 antagonists affect the expression of UROS. Furthermore, dual-luciferase reporter gene experiments confirmed the relationship between TCON_00025035, miR-101, and UROS. The regulatory relationship between TCONS_00025035 and miR-101 is negative, and the regulatory relationship between miR-101 and UROS is also negative. In summary, we verified the function of UROS through RNA interference, qPCR, in situ hybridization, and melanin content detection. We speculated that there was a negative relationship between miR-101 and UROS, and there was also a negative relationship between TCONS_00025035 and miR-101. TCONS_00025035 might regulate UROS through the regulation of miR-101, and UROS might also regulate other pigmentation-related genes and affect the formation of pigments, thereby influencing porphyrin and melanin formation in Manila clam.

Identification of a T-box transcription factor TBX2 and its negative regulatory role in melanin production in the Pacific oyster Crassostrea gigas

Oyster shells exhibit varying color patterns—black, white, or black and white striations—attributable to differences in melanin content and distribution. In this study, we identified a new homolog of TBX2, a member of the T-box transcription factor family, in the Pacific oyster (Crassostrea gigas) named CgTBX2. The mRNA expression of CgTBX2 was higher in tissues from white-shelled oysters than in those from black-shelled oysters. Knockdown of CgTBX2 in C. gigas significantly upregulated the expression of two key genes involved in melanin synthesis, CgTYR and CgTYR2. The tissue expression profile revealed that CgTBX2 is highly expressed in gill and mantle. CgTBX2 protein is mainly localized in the nucleus and can combine with TBX-binding elements (TBEs) present in the CgOCA2 promoter. CgTBX2 repressed the activity of the CgOCA2 promoter, with a strong transcriptional inhibition effect on the −2000 to −878 and −211 to −1 regions. Furthermore, the combination of CgTBX2 with GTTGACACCTT sequence is responsible for the transcriptional inhibition on the −211 to −1 region of the CgOCA2 promoter. Our findings reveal that CgTBX2, a novel regulator of melanin pigmentation in C. gigas, negatively regulates melanin deposition by inhibiting tyrosinase genes expression and repressing the transcriptional activity of the CgOCA2 promoter.

Inhibitory Effect of Tanshinone IIA Extracted from Radix Salviae miltiorrhizae on Melanoma B16F10 Cells

In this study, we investigate the inhibitory effects of Tanshinone IIA on the proliferation and migration of B16F10 melanoma cells and its potential mechanism of action. We cultured B16F10 melanoma cells in vitro and treated them with varying concentrations of tanshinone IIA. The inhibitory effect of tanshinone IIA on B16F10 cells was assessed using the CCK-8 assay, employing methyl thiazolyl tetrazolium. Melanin content was determined by the NaOH cleavage method, while expression levels of melanin-related proteins were analyzed by Western blotting, and migration-related proteins were quantified using ELISA. When the concentration of Tanshinone IIA reached 20 and 40 μg/mL, there was a decrease in the survival rate of B16F10 melanoma cells. The proliferation inhibition rate of B16F10 melanoma cells gradually increased with the duration of drug action and the concentration of Tanshinone IIA. After 48 hours, there was an increase in melanin content. A comparison of melanin synthesis at the three concentrations yielded an F value of 61.820 and P <0.001. The relative expression levels of TYR, TRP-1, TRP-2, and MITF increased when treated with different concentrations of Tanshinone IIA (P < 0.05). MMP-2 and MMP-9 were downregulated when the concentration of Tanshinone IIA was at 40 and 80 μg/mL respectively (P <0.05). In conclusion, our study demonstrated the inhibitory effects of Tanshinone IIA on growth, proliferation, migration, and melanin synthesis in B16F10 melanoma cells. However, further research is needed to elucidate the specific signal transduction pathway activated by Tanshinone IIA.

Novel deoxyhypusine synthase (DHPS) inhibitors target hypusination-induced vasculogenic mimicry (VM) against malignant melanoma

Vasculogenic mimicry (VM) contributes factor to the poor prognosis of malignant melanoma. Developing deoxyhypusine synthase (DHPS) inhibitors against melanoma VM is clinically essential. In this study, we optimized and synthesized a series of compounds based on the candidate structure, and the hit compound 7k was identified through enzyme assay and cell viability inhibition screening. Both inside and outside the cell, 7k's ability to target DHPS and its high affinity were demonstrated. Molecular dynamics and point mutation indicated that mutations of K329 or V129 in DHPS abolish 7k's inhibitory activity. Using PCR arrays, solid-state antibody microarrays, and angiogenesis assays investigated 7k's impact on melanoma cells to reveal that DHPS regulates melanoma VM by promoting FGFR2 and c-KIT expression. Surprisingly, 7k was discovered to inhibit MC1R-mediated melanin synthesis in the zebrafish. Pharmacokinetic evaluations demonstrated 7k's favorable properties, and xenograft models evidenced its notable anti-melanoma efficacy, achieving a TGI of 73 %. These results highlighted DHPS as key in melanoma VM formation and confirmed 7k's potential as a novel anti-melanoma agent.

Physico-chemical characteristics of melanins culture medium Inocutis dryophila (Berk) Flasson & Niemela

The purpose of the study was to investigate the effect of light treatment on the synthesis of endomelanins from the mycelium of Inocutis dryophila in a liquid culture medium. To identify the effect of light on the synthesis of melanins, the mycelium of Inocutis dryophila was cultivated in a liquid medium in the dark and using blue light treatment. As a result, two types of melanins IDM-1 and IDM-2 were obtained. It has been established that the light factor influences the quantitative release of melanins from the mycelium of Inocutis dryophila into the culture liquid. The use of blue light resulted in lower melanin content in the culture fluid than in the dark. Ultraviolet and infrared spectrometry showed that both types of melanins have typical spectra and graphs for fungal melanins. Infrared spectrometry showed that treatment of mycelium with blue light led to deformation of IDM-1. It was revealed that IDM-2 melanins exhibit greater antiradical activity than IDM-1 melanins. Thus, light treatment of Inocutis dryophila mycelium in a liquid medium affects the quantitative release of melanins into the culture liquid, promotes a change in the structure, as well as manifestation of a biological effect.

Apigenin Ameliorates H2O2-Induced Oxidative Damage in Melanocytes through Nuclear Factor-E2-Related Factor 2 (Nrf2) and Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (Akt)/Mammalian Target of Rapamycin (mTOR) Pathways and Reducing the Generation of Reactive Oxygen Species (ROS) in Zebrafish

Background: Apigenin is one of the natural flavonoids found mainly in natural plants, as well as some fruits and vegetables, with celery in particular being the most abundant. Apigenin has antioxidant, anti-tumor, anti-inflammatory, and anticancer effects. In this research, we attempted to further investigate the effects of apigenin on the mechanism of repairing oxidative cell damage. The present study hopes to provide a potential candidate for abnormal skin pigmentation disorders. Methods: We used 0.4 mM H2O2 to treat B16F10 cells for 12 h to establish a model of oxidative stress in melanocytes, and then we gave apigenin (0.1~5 μM) to B16F10 cells for 48 h, and detected the expression levels of melanin synthesis-related proteins, dendritic regulation-related proteins, antioxidant signaling pathway- and Nrf2 signaling pathway-related proteins, autophagy, and autophagy-regulated pathways by immunoblotting using Western blotting. The expression levels of PI3K/Akt/mTOR proteins were measured by β-galactosidase staining and Western blotting for cellular decay, JC-1 staining for mitochondrial membrane potential, and Western blotting for mitochondrial fusion- and mitochondrial autophagy-related proteins. Results: Apigenin exerts antioxidant effects by activating the Nrf2 pathway, and apigenin up-regulates the expression of melanin synthesis-related proteins Tyr, TRP1, TRP2, and gp100, which are reduced in melanocytes under oxidative stress. By inhibiting the expression of senescence-related proteins p53 and p21, and delaying cellular senescence, we detected the mitochondrial membrane potential using JC-1, and found that apigenin improved the reduction in mitochondrial membrane potential in melanocytes under oxidative stress, and maintained the normal function of mitochondria. In addition, we further detected the key regulatory proteins of mitochondrial fusion and division, MFF, p-DRP1 (S637), and p-DRP1 (S616), and found that apigenin inhibited the down-regulation of fusion-associated protein, p-DRP1 (S637), and the up-regulation of division-associated proteins, MFF and p-DRP1 (S616), due to oxidative stress in melanocytes, and promoted the mitochondrial fusion and ameliorated the imbalance between mitochondrial division and fusion. We further detected the expression of fusion-related proteins OPA1 and Mitofusion-1, and found that apigenin restored the expression of the above fusion proteins under oxidative stress, which further indicated that apigenin promoted mitochondrial fusion, improved the imbalance between mitochondrial division and fusion, and delayed the loss of mitochondrial membrane potential. Apigenin promotes the expression of melanocyte autophagy-related proteins and the key mitochondrial autophagy proteins BNIP3L/Nix under oxidative stress, and activates the PINK1/Parkin signaling pathway by up-regulating the expression of autophagy-related proteins, as well as the expression of PINK1 and Parkin proteins, to promote melanocyte autophagy and mitochondrial autophagy. Conclusions: Apigenin exerts anti-melanocyte premature aging and detachment effects by promoting melanin synthesis, autophagy, and mitochondrial autophagy in melanocytes, and inhibiting oxidative cell damage and senescence.

Glycosphingolipids Associated Metabolic Disorders

Lipids play diverse roles in sustaining life, including energy storage, hormonal balance, and cellular communication. Alterations in lipid metabolism can lead to various disorders, including diabetes, atherosclerosis, cancer, and neurodegenerative diseases. Among these disorders, lysosomal storage disorders (LSDs) related to glycosphingolipids metabolism present significant challenges. This review systematically analyzes the current literature on LSDs, focusing on classification, clinical presentations, diagnostic advancements, available treatments, and emerging therapeutic strategies. Glycosphingolipids biosynthesis, particularly its role in viral dissemination and melanin synthesis, underscores its significance in health and disease. Additionally, the review delves into specific LSDs, such as Fabry disease, Gaucher disease, Sandhoff disease, Tay-Sachs disease, and Krabbe disease, highlighting their pathophysiology, prevalence, and treatment options. Enzyme replacement therapy and hematopoietic stem cell transplantation are mainstays in LSD treatment, but gene therapy shows promise. Furthermore, the review explores the role of glycosphingolipids in non-communicable diseases like diabetes, cancer, atherosclerosis, lupus, Alzheimer's, Parkinson's disease, and influenza. Understanding glycosphingolipid metabolism offers insights into disease mechanisms and therapeutic targets, paving the way for improved treatments and ultimately enhancing patient outcomes.

Cell wall nanoparticles from hyphae of Alternaria infectoria grown with caspofungin, nikkomycin, or pyroquilon trigger different activation profiles in macrophages.

Alternaria infectoria causes opportunistic human infections and is a source of allergens leading to respiratory allergies. In this work, we prepared cell wall nanoparticles (CWNPs) as a novel approach to study macrophage immunomodulation by fungal hyphal cell walls. A. infectoria was grown in the presence of caspofungin, an inhibitor of β(1,3)-glucan synthesis; nikkomycin Z, an inhibitor of chitin synthases; and pyroquilon, an inhibitor of dihydroxynaphthalene (DHN)-melanin synthesis. Distinct CWNPs were obtained from these cultures, referred to as casCWNPs, nkCWNPs, and pyrCWNPs, respectively. CWNPs are round-shaped particles with a diameter of 70-200 nm diameter particles that when added to macrophages are taken up by membrane ruffling. CWNPs with no DHN-melanin and more glucan (pyrCWNPs) caused early macrophage activation and lowest viability, with the cells exhibiting ultrastructural modifications such as higher vacuolization and formation of autophagy-like structures. CasCWNPs promoted the highest tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) increase, also resulting in the release of partially degraded chitin, an aspect never observed in macrophage-like cells and fungi. After 6 h of interaction with CWNPs, only half were viable, except with control CWNPs. Overall, this work indicates that compounds that modify the fungal cell wall led to CWNPs with new properties that may have implications for the effects of drugs during antifungal therapy. CWNPs provide a new tool to study the interaction of hyphal fungal cell wall components with phagocytic cells and enable to show how the modification of cell wall components in A. infectoria can modulate the response by macrophages.IMPORTANCEAlternaria species are ubiquitous environmental fungi to which the human host can continuously be exposed, through the inhalation of fungal spores but also of fragments of hyphae, from desegregated mycelia. These fungi are involved in hypersensitization and severe respiratory allergies, such as asthma, and can cause opportunistic infections in immunodepressed human host leading to severe disease. The first fungal structures to interact with the host cells are the cell wall components, and their modulation leads to differential immune responses. Here, we show that fungal cells grown with cell wall inhibitors led to cell wall nanoparticles with new properties in their interaction with macrophages. With this strategy, we overcame the limitation of in vitro assays interacting with filamentous fungi and showed that the absence of DNH-melanin leads to higher virulence, while caspofungin leads to cells walls that trigger higher hydrolysis of chitin and higher production of cytokines.

Tyrp1 is the mendelian determinant of the Axolotl (Ambystoma mexicanum) copper mutant

Several dozen Mendelian mutants have been discovered in axolotl (Ambystoma mexicanum) populations, including several that affect pigmentation. Four recessive mutants have been described in the scientific literature and genes for three of these have been identified. Here we describe and genetically dissect copper, a mutant with an albino-like phenotype known only from the pet trade. We performed a cross segregating copper and wildtype color phenotypes and used bulked segregant RNA-Seq to identify a region on chromosome 6 that was enriched for single-nucleotide polymorphisms (SNPs) between the color phenotypes. This region included Tyrosinase-like Protein 1 (Tyrp1), a melanin synthesis protein that when mutated, is associated with lighter than black melanin coloration in animal models and oculocutaneous albinism in humans. Inspection of RNA-Seq reads identified a single nucleotide deletion that is predicted to change the coding frame, introduce a premature stop codon in exon 6 and yield a truncated Tyrp1 protein in copper individuals. Using CRISPR-Cas9 editing, we show that wildtype Tyrp1 crispants exhibit copper pigmentation, thus confirming Tyrp1 as the copper locus. Our results suggest that commercial and hobbyist axolotl populations may harbor useful mutants for biological research.

1-Acetyl-β-Carboline from a Jeju Gotjawal Strain Lentzea sp. JNUCC 0626 and Its Melanogenic Stimulating Activity in B16F10 Melanoma Cells.

The genus Lentzea is a prolific source of bioactive and structurally diverse secondary metabolites. We isolated a novel strain, Lentzea sp. JNUCC 0626, from Hwasun Gotjawal on Jeju Island, Korea. Based on 16S rRNA partial gene sequence analysis, strain JNUCC 0626 is closely related to Lentzea isolaginshaensis NX62 (99.41% similarity), Lentzea pudingi DHS C021 (99.31%), and Lentzea cavernae SYSU K10001 (99.26%). From the fermentation broth of JNUCC 0626, we isolated 1-acetyl-β-carboline, whose structure was established using IR, HR-ESI-MS, and 1D- and 2D-NMR techniques. 1-acetyl-β-carboline was found to activate melanogenesis in mouse B16F10 cells without cytotoxicity at concentrations up to 50 μM. At this concentration, the compound increased melanin content by 27.44% and tyrosinase activity by 240.64% compared to the control, by upregulating key melanogenic enzymes, including tyrosinase, TRP-1, TRP-2, and microphthalmia-associated transcription factor (MITF), a central regulator of melanogenesis. In addition, 1-acetyl-β-carboline significantly inhibited ERK phosphorylation, reducing it by 20.79% at a concentration of 12.5 μM and by 25.63% at 25 μM. This inhibition supports the hypothesis that 1-acetyl-β-carboline enhances melanin synthesis by upregulating MITF and melanogenic enzymes via the ERK signaling pathway. This study aimed to isolate and identify 1-acetyl-β-carboline from a novel strain of Lentzea sp. JNUCC 0626, discovered in Gotjawal, Jeju Island, and to evaluate its effect on melanin production in B16F10 melanoma cells. Skin irritation tests on 32 subjects confirmed its safety for topical use, and the findings suggest that 1-acetyl-β-carboline, which enhances melanogenesis without cytotoxicity, holds promise as a therapeutic agent for hypopigmentation-related conditions or as a cosmetic ingredient.

The research of nicotinamide and β-arbutin on reducing melanin content in the skin of leopard coral grouper (Plectropomus leopardus)

Body color is an important economic characteristic of leopard coral grouper (Plectropomus leopardus). In this study, we tried to make the red color more visible on the skin by reducing the melanin level, and aimed to investigate the possible mechanism of nicotinamide and β-arbutin on reducing melanin content in the skin of P. leopardus. 0.5 % nicotinamide or 0.5 % β-arbutin was added to the basal feed formulation to feed P. leopardus for 60 days. After nicotinamide or β-arbutin added feeding, the time for P. leopardus to maintain uniform body color was significantly longer. The melanin content in the skin of P. leopardus was significantly reduced, and the number of melanin particles was reduced. In skin, the enzyme activities of superoxide dismutase (SOD) and catalase (CAT) decreased, and the content of malondialdehyde (MDA) increased. The mRNA expression of TYR, Sox10 and Mitf related to melanin synthesis and proliferation and differentiation decreased. The apoptosis-related gene Bax was upregulated, the Bcl-2 gene was down-regulated, and Bax/Bcl-2 > 1. The content of tyrosinase decreased and the content of melanin metabolizing enzyme increased, and the effect of nicotinamide was more obvious than that of β-arbutin. In summary, nicotinamide or β-arbutin added feeding increased the oxidative stress and the apoptosis level of the skin, increased the metabolism of melanin, decreased the synthesis and differentiation of melanin, thus reduced the content of melanin and the number of melanin particles in the skin. This study provided a new basis for the body color regulation of cultured P. leopardus.

Ionic liquid combined with cationic liposome co-delivers microphthalmia-associated transcription factor small interfering RNA to regulate melanogenesis

Suppressing allele-specific genes using small interfering RNAs (siRNAs) can effectively whiten skin by influencing cellular gene and protein expression. Topical delivery of siRNA is a promising alternative to injections for RNA interference. However, the barrier function of the skin hinders the effective penetration of siRNA. Here, we report, a novel approach to achieve the transdermal delivery of effective siRNA doses using a complementary synergistic strategy of an ionic liquid (IL) and cationic liposome (CL). Microphthalmia-associated transcription factor (MITF) siRNA molecules were formed through electrostatic adsorption of the IL and CL to form positively charged nanocomposites, which were named IL-CL/p-siM. IL-CL/p-siM has a particle size of 171.47 nm, ζ-potential of 29.94 mV, high encapsulation rate of 92.11 %, and pH-sensitive release properties. In vitro studies on porcine skin confirmed the additive/synergistic effect of this strategy in enhancing epidermal and dermal penetration. This combination enabled superior transfection efficiency and cell viability while inhibiting melanin synthesis in skin melanocytes by downregulating the expression of genes downstream of MITF, namely tyrosinase-related protein-1, tyrosinase, and tyrosinase-related protein-2, which are associated with the melanocortin 1 receptor. We also conducted clinical studies that demonstrated its potential in treating melasma and its anti-melanotic efficacy. To summarize, IL-CL/p-siM represents a simple, personalized, and scalable platform for effective local delivery of siRNA to treat skin complications.

UV-Protection Effect of Nanoemulgel Formulation from Moringa oleifera Lam. Leaf Extracts in Rattus novergicus

Exposure to sunlight (UV radiation) can harm the skin, leading to cancer and tissue damage. The body’s natural defense involves activating hormones that stimulate melanin synthesis to reduce cellular damage. Moringa oleifera Lam. leaves, rich in flavonoids and phenolic compounds, are promising UV-protection agents. This study assessed the efficacy of nanoemulgel formulations containing M. oleifera leaf extract through in vitro and in vivo assays. Twenty-five rats were divided into five groups, including formulations with 2%, 3%, and 4% M. oleifera extract, a negative control, and a positive control with Azarine Sunscreen Gel SPF 45. The nanoemulsions had appropriate size and quality, with the highest SPF observed at 4% concentration (7.95±0.06). According to FDA classification, these formulations fall within the 'extra' SPF category (6<SPF<8). However, melanin scores in the nanoemulgel groups were comparable to the untreated control, and the 4% concentration (44.4±16.3) did not match the protection provided by commercial sunscreen (10.0±1.58). These findings suggest M. oleifera has potential for photoprotection, but further optimization is needed.

Trifolirhizin from Sophora flavescens as a Promising Medicinal Agent: An Update on Biological Significance, Pharmacological Activity, and Analytical Applications

Sophora flavescens is an important medicinal plant found in India and East Asia, primarily in China, Japan, Korea and Russia. Trifolirhizin is an active phytochemical of Sophora flavescens and other Chinese medications such as Zeng-Sheng-Ping, Xian-Lian-Ke-Li, ASHMI, Ling Zhi, Ku Shen, and Gan Cao, Ku Shen injection and Zeng Sheng Ping tablets. Sophora flavescens have numerous therapeutic benefits against hematochezia, jaundice, liver disorders, dysentery, oliguria, asthma, eczema, vulvar swelling, and inflammatory complications. The purpose of the present review is to summarize the scientific information on trifolirhizin for their biological potential, pharmacological activities, and analytical aspects of medicine. Scientific information on trifolirhizin has been collected from various scientific databases such as Scopus, Science Direct, PubMed, and Google Scholar. Further, the present review summarized the pharmacological activities of trifolirhizin and their different molecular mechanisms and analytical aspects. The scientific data on trifolirhizin signified the biological potential and therapeutic effectiveness of trifolirhizin in medicine. Present review signified the presence of trifolirhizin in the Sophora flavescens. Sophora flavescens has been shown to be effective against ulcers, chronic bronchitis, acne, atopic dermatitis, chronic hepatitis, enteritis, pyogenic infection and other inflammatory diseases. Furthermore, the present review also summarized the biological potential of trifolirhizin in gastric cancer, hepatocellular carcinoma, colorectal cancer, apoptosis, ulcerative colitis, and asthma. However, hepatoprotective effects, anti-inflammatory effects, wound healing potential, and efficiency of melanin synthesis were also revealed. In addition, this review also summarizes the molecular mechanisms of trifolirhizin and their pharmacokinetic and metabolic parameters. This review also describes the analytical aspects of trifolirhizin in medicine. This review will be useful to the entire research community exploring the biological potential of trifolirhizin in medicine. However, scientific studies require comprehensive and detailed data on trifolirhizin evaluation, quality control, toxicity, and clinical efficacy.