Search Results (107)

Picnomon acarna (L.) Cass. is a Mediterranean medicinal plant with limited phytochemical and bioactivity characterisation. In this study, methanolic extracts obtained by maceration (MAC), Soxhlet (SOE), and ultrasound-assisted extraction (UAE) were comparatively investigated to determine their phytochemical composition and biological potential. Liquid chromatography–electrospray ionisation–tandem mass spectrometry (LC–ESI–MS/MS) analysis identified and quantified 24 phenolic compounds, with hesperidin, chlorogenic acid, and hyperoside as the dominant constituents. The maceration extract exhibited the highest total phenolic content (29.06 mg GAE/g extract) and showed superior antioxidant performance across six complementary assays [2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), ferric reducing antioxidant power (FRAP), phosphomolybdenum, and ferrous-ion chelation), reflected by the highest relative antioxidant capacity index (RACI = 0.93). Enzyme inhibition assays revealed extraction-dependent activity patterns: Soxhlet and ultrasound extracts demonstrated stronger acetylcholinesterase inhibition (IC₅₀ ≈ 1.23 mg/mL), while Soxhlet extract showed the most potent tyrosinase (AChE) inhibition (IC₅₀ = 1.48 mg/mL). α-Amylase inhibition was comparable among extracts (IC₅₀ = 1.90–2.03 mg/mL). Pearson correlation analysis indicated strong relationships between major phenolics and antioxidant activity. Molecular docking further supported these findings, showing favourable binding affinities of hesperidin, hyperoside, and chlorogenic acid toward α-amylase and acetylcholinesterase, while only chlorogenic acid and hyperoside demonstrated favourable interactions with tyrosinase-related protein-1 (TYRP1), whereas hesperidin did not exhibit a meaningful binding affinity. Overall, the results demonstrate that the extraction strategy significantly influences the phenolic composition and multi-target bioactivity of P. acarna, highlighting its potential as a source of natural antioxidant and enzyme-modulating compounds. Full article

Tyrosinase promotes excessive deposition of melanin, which may lead to severe skin diseases. Passiflora edulis f. edulis seeds have been reported to be rich in diverse bioactive constituents exhibiting potential tyrosinase inhibitory activity. However, the principal bioactive constituents responsible for tyrosinase inhibitory activity and its underlying mechanisms remain largely unclear. Therefore, this study aimed to: (1) optimize SC-CO₂ extraction of Passiflora edulis f. edulis seed oil (PFSO) for maximum yield and bioactive preservation; (2) comprehensively characterize its physicochemical and phytochemical profile; (3) elucidate the tyrosinase inhibition mechanism through kinetic, spectroscopic, and computational approaches; and (4) validate its safety, antioxidant, and anti-pigmentation efficacy in a zebrafish model. PFSO exhibited a yield of 24.96%, with a high content of unsaturated fatty acids (88.03%, mainly linoleic acid at 74.40%). The oil inhibited tyrosinase via a reversible mixed-type mechanism (IC₅₀ = 1.12 mg/mL). Fluorescence spectroscopy and molecular docking revealed that linoleic acid binds to LYS180 and β-sitosterol binds to TYR78, mainly driven by hydrogen bonding and hydrophobic interaction, which changed the microenvironment of tryptophan residues and indicated static quenching. Further validation experiments revealed that the major constituent, linoleic acid, exhibited only weak inhibitory activity against tyrosinase (IC₅₀ = 29.44 mg/mL), whereas the key component β-sitosterol markedly suppressed tyrosinase activity (IC₅₀ = 46.43 μg/mL). In vitro assays demonstrated PFSO’s significant efficacy in reducing the melanin content and tyrosinase activity in α-MSH-stimulated B16F10 murine melanoma cells. In vivo experiments in zebrafish that received dietary supplementation with PFSO confirmed that PFSO (≤5 mg/mL) reduced ROS production, suppressed melanin deposition, inhibited tyrosinase activity, and downregulated the expression of melanogenesis-related genes (TYR, TYRP1, TYRP2, MITF). This study provides, for the first time, a comprehensive elucidation of PFSO’s potential as a natural tyrosinase inhibitor, integrating extraction optimization, multicomponent characterization, multimodal inhibition analysis, and in vivo validation. Full article

As primary producers in aquatic ecosystems, microalgae function not only as a natural source of nourishment for several economically important aquatic species but also as reservoirs of bioactive molecules. Microalgae can secrete exosome-like nanoparticles that transport functional biomolecules, such as proteins and nucleic acids, into the extracellular milieu, thereby mediating intercellular signaling and eliciting ecological or biomedical responses. Although plant-derived exosome-like nanoparticles have attracted attention for their utility in drug delivery and dermatology, the functional properties of microalgae-derived nanoparticles—particularly from species extensively applied in aquaculture—remain inadequately characterized. In this study, exosome-like nanovesicles were isolated from Nannochloropsis oculata (N-ELNs), a microalgal species widely used in aquaculture, and their skin-whitening potential was evaluated using the B16-F10 mouse melanoma cell model. The highest N-ELN yield was observed during the adaptation, exponential, and stationary growth phases. Uptake analyses confirmed the efficient internalization of N-ELNs by B16-F10 cells. Cell counting kit-8 assays indicated that N-ELNs exhibited no cytotoxic effects on melanoma cells or normal human dermal fibroblasts (HFF-1). Scratch wound healing assays revealed that N-ELNs exerted no significant effect on cellular migration. In B16-F10 cells, N-ELNs suppressed tyrosinase activity by downregulating Mitf and its downstream genes Tyr and Tyrp1, resulting in a substantial reduction in melanin synthesis (p < 0.05). The inhibitory effects of N-ELNs on melanin production, tyrosinase activity, and gene expression of Tyr, Tyrp1, and Mitf were comparable to those of the positive control, arbutin. Collectively, these findings suggest that N. oculata exhibits promising skin-whitening properties, providing a novel perspective for clinical applications and supporting the high-value utilization of the microalgae aquaculture industry. Full article

Tyrosinase is a key enzyme in melanin biosynthesis, and natural inhibitors have potential therapeutic and cosmetic applications. Lysinibacillus sp. JNUCC 52, a member of the Bacillaceae family, shows potential for producing bioactive secondary metabolites. However, the tyrosinase inhibitory potential of metabolites from this strain has not been previously reported. This study investigates its genomic features, secondary metabolites, and tyrosinase inhibitory activity to identify promising enzyme inhibitors. Integrated COG, GO, and KEGG annotation revealed a metabolically robust network supporting secondary metabolite biosynthesis. Chemical investigation of the ethyl acetate extract yielded five known compounds, among which cyclo(L-Pro-L-Leu) displayed the strongest tyrosinase inhibition (IC₅₀ = 79.5 ± 2.3 μM), whereas uracil showed weaker activity. In silico ADMET and drug-likeness analyses suggested favorable pharmacokinetic properties and compliance with major drug-likeness rules for cyclo(L-Pro-L-Leu). Molecular docking and molecular dynamics simulations demonstrated stable binding to mushroom tyrosinase (mTYR) and human TYRP1, supported by MM/GBSA and residue decomposition analyses identifying key stabilizing residues. Together, these results provide mechanistic insight into tyrosinase inhibition and highlight cyclo(L-Pro-L-Leu) as a minimal lead-like scaffold, while establishing strain JNUCC 52 as a promising microbial source of bioactive metabolites. Full article

Silkie (SK) chickens, valued for dark meat, serve as a model to study melanin deposition in muscle. Integrated transcriptomics and metabolomics of SK vs. Arbor Acres (AA) broiler pectoralis were used to identify key molecular drivers of meat color. All birds were cage-raised under standardized temperature and light conditions with free access to feed and water. Pectoralis muscle samples were collected from 24-day-old healthy SK and AA chickens (n = 6). Transcriptome profiling identified 488 differentially expressed genes in SK chickens, with seven conserved melanogenesis genes (TYRP1, MLANA, TYR, MLPH, EDNRB2, PMEL, GPNMB) consistently upregulated across dark-pectoralis breeds, and melanogenesis and WNT pathways were activated. Co-expression network analysis highlighted SOX10 as a key hub regulator. Metabolomics quantified 129 differentially abundant metabolites. A critical finding was the significant depletion of L-tyrosine and its derivatives in SK muscle, despite upregulated melanogenesis genes. It indicates intense metabolic flux toward pigment synthesis. Integrated analyses converged on tyrosine metabolism and redox pathways: oxidized glutathione and p-coumaric acid correlated negatively with pigment deposition, while ADP-ribose and pyridoxal correlated positively. Additionally, novel inhibitors PNMT and HIBADH may modulate melanin deposition. These findings reveal a trade-off between pigment deposition and redox balance, providing molecular markers for poultry melanin-related trait improvement. Full article

Plant-derived exosome-like extracellular vesicles (PELVs) have recently emerged as novel bioactive materials. Although members of the Orchidaceae family have been reported to possess various biological activities and are widely used as cosmetic ingredients, no studies to date have investigated exosome-like extracellular vesicles derived from Phalaenopsis species. In the present study, we report for the first time a novel exosome-like extracellular vesicles preparation isolated from Phalaenopsis aphrodite (called Exorigin^® OR) and characterize its physical and biological properties. The purified vesicles exhibited a spherical shape surrounded by a bilayered membrane with an average particle size of approximately 98 nm and expressed a CD9 marker. Fluorescent labeling with BODIPY TR indicated that Exorigin^® OR can be internalized by cells. In in vitro assays, Exorigin^® OR alleviated hydrogen peroxide-induced damage in keratinocytes and inhibited melanin production in melanocytes, possibly associated with the downregulation of Tyrp1 expression as shown by qPCR analysis. Moreover, reconstructed human epidermis and cornea-like epithelium models demonstrated that Exorigin^® OR is non-irritant. Collectively, these findings suggest that Exorigin^® OR represent a promising and safe bioactive ingredient for promoting skin health in cosmeceutical applications. Full article

The liquid egg processing industry generates a significant amount of solid byproduct known as chalaza (CHA), which is rich in sialic acid and exhibits notable biological activity. In this study, the preparation process, N-glycan profile, and skin-whitening activity of CHA-derived glycopeptides (CHAH) were investigated. By comparing the hydrolysis efficiency of trypsin, alcalase, and papain, a dual-enzyme hydrolysis strategy was developed: initial hydrolysis with 1.5% trypsin for 3 h, followed by treatment with 1% papain for 2 h. The resulting CHAH exhibited both a high hydrolysis yield and strong antioxidant activity. The sialic acid content in CHAH reached 1.96% (w/w), and 14 distinct N-glycan chain structures were identified. The whitening effect of CHAH was assessed using a combined approach involving an in vitro B16 cell model and an in vivo zebrafish model. CHAH was found to inhibit tyrosinase activity and reduce melanin production in a concentration-dependent manner. Mechanistic studies revealed that CHAH acts by significantly downregulating the expression of key genes involved in melanin synthesis, including MITF, TYR, TYRP1, and TYRP2. This study establishes an efficient preparation method for CHAH, elucidates its skin-whitening efficacy and underlying mechanism, and provides experimental support for the potential industrial application of CHAH as an active ingredient in skincare products. Full article

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a small neuropeptide detected first in the hypothalamo–hypophyseal system; recently, it has also been identified in peripheral organs and in tumours. It is well demonstrated that PACAP exerts cell- and tissue-protecting effects in various stressful conditions and helps to maintain tissue homeostasis. In melanoma, the anti-invasive effect of PACAP has been demonstrated; however, there is also existing sporadic data which proves PACAP plays a role in melanoma progression. The major goal of our study was to investigate the signalling targets of PACAP in A2058 and WM35 melanoma cell lines in vitro. Various molecular players of melanocyte differentiation and function responded to PACAP application. SOX9 expression increased while SOX10 expression decreased and CREB signalling did not change. The expression level of TYRP1 decreased, while DCT elevated, and MITF expression showed changes at the mRNA level and in its subcellular localisation. In contrast, the amount of hyaluronan (HA) and expressions of its synthases, as well as RHAMM, increased, indicating the role of PACAP in secretion of an HA-rich matrix. In parallel with these results, we detected elevated hyaluronidase2 (Hyal2) expression in the presence of PACAP. On the other hand, alfaV and beta3 integrin expressions did not alter significantly. Our results demonstrate that exogenous PACAP modulates the expression of multiple target molecules in melanoma cells. Some of the significantly responding molecules take part in hyaluronan homeostasis, suggesting an effect of PACAP on tumour matrix composition, through which it can modulate invasiveness of melanoma cells. Full article

This study investigated muscle quality differences between wild-type (WT) and yellow-mutant (YM) Triplophysa siluroides. Texture analysis showed WT T. siluroides had significantly greater hardness, gumminess, and resilience than YM. Histological and biochemical analyses ruled out myofiber diameter/density as drivers, instead identifying reduced collagen in YM as key, as confirmed by Picrosirius red staining, collagen quantification, and transmission electron microscopy. Transcriptomic and proteomic analyses revealed that TGF-β/BMP pathway suppression in YM resulted in downregulation of core molecules (e.g., BMP2 and SMAD1), collagen-related genes (e.g., COL1A1a and COL1A1b), and ECM-related genes (e.g., TNC and FN1), potentially influencing collagen synthesis and ECM homeostasis. Notably, melanin gene TYRP1 was also downregulated in YM T. siluroides, suggesting a link between pathway suppression, muscle quality alteration, and body pigmentation. The potential role of the BMP2-SMAD1-TYRP1 axis in the association between muscle quality and body colour provides novel mechanistic insights, offering molecular targets for the breeding of T. siluroides with superior commercial traits. Full article

Excessive melanin production causes hyperpigmentation disorders such as freckles, melasma, and age spots, affecting appearance and quality of life. Tyrosinase is the key enzyme controlling melanin synthesis, and natural compounds are being explored as effective tyrosinase inhibitors. Fisetin, a dietary flavonoid found in fruits and vegetables like grapes and onions, is known for its anti-inflammatory and anticancer properties, but its anti-melanogenic activity remains unclear. This study demonstrated that fisetin, up to 60 μM, is non-toxic and significantly decreases tyrosinase activity and melanin content in human melanoma cells. Mechanistically, fisetin activates PKCα, leading to phosphorylation and degradation of β-catenin, thereby downregulating MITF expression. Additionally, it activates ERK and AKT/GSK3β pathways, promoting ubiquitination and proteasomal degradation of MITF, resulting in reduced levels of tyrosinase, TRP-1, and TRP-2. The proteasome inhibitor MG132 confirmed that fisetin accelerates β-catenin and MITF degradation. Additionally, inhibition of the PI3K/AKT pathway by LY294002 or the ERK pathway by PD98059 reversed fisetin’s reduction of tyrosinase activity and melanin synthesis, further verifying the participation of these pathways. Computational docking integrated with deep learning-based CNN scoring revealed that fisetin interacts with PKCα, β-catenin, tyrosinase, and TYRP1. Collectively, these findings suggest that fisetin exerts multi-targeted inhibitory effects on melanogenesis, highlighting its potential as a therapeutic and cosmetic agent for hyperpigmentation. Full article

Plumage coloration in ducks (Anas platyrhynchos) represents a complex polygenic trait of significant economic and biological importance in commercial poultry production. This comprehensive review synthesizes current knowledge on the genetic mechanisms underlying feather coloration in domestic ducks, with particular emphasis on melanin biosynthesis pathways and their regulatory networks. We systematically analyzed recent advances including genome-wide association studies, RNA sequencing, whole-genome resequencing, and population genetics approaches that have identified key candidate genes controlling duck pigmentation patterns. The melanogenesis pathway emerges as the central regulatory network, with nine core genes (MITF, MC1R, TYR, TYRP1, DCT, SOX10, KIT, EDNRB2, and MLANA) consistently associated with plumage coloration across multiple duck populations. The MITF functions as the master regulator, coordinating expression of the enzymatic triad (TYR, TYRP1, DCT) responsible for melanin synthesis, while MC1R serves as the primary receptor controlling eumelanin versus pheomelanin production ratios. Epistatic interactions between MITF and MC1R demonstrate the complexity of color inheritance, with MITF exhibiting dominant effects over MC1R in determining white versus black plumage phenotypes. Functional enrichment analyses confirm these genes’ central roles in melanin biosynthetic processes and tyrosine metabolism pathways. Additionally, recent studies have revealed the importance of regulatory mechanisms, including epigenetic modifications and tissue-specific expression patterns, in modulating final coloration phenotypes. Understanding these genetic determinants provides valuable insights for selective breeding programs aimed at optimizing esthetic and economic traits in duck production. This review establishes a foundation for future research in avian pigmentation genetics and offers practical applications for improving breeding efficiency and product quality in the global duck industry. Full article

The northern snakehead (Channa argus) is an important economic fish species that holds a significant position in Chinese aquaculture due to its high nutritional value, fast growth, and anti-hypoxia capacity. There is a natural albino-mutant (AM) C. argus strain. Albinism, a stable genetic trait characterized by loss of body pigmentation, provides a unique opportunity to study the molecular mechanisms of vertebrate coloration. This study investigates the molecular mechanisms underlying albinism in C. argus through skin transcriptomic analyses of wild type (WT) and AM individuals. Morphological and histological analysis revealed no significant phenotypic difference between WT and AM in early development, whereas adult AM exhibited a severe reduction in melanocytes. Through RNA sequencing of skin tissues from WT-adult, AM-adult, and AM-15dpf, a total of 10,891 differentially expressed genes (DEGs) were identified. Through DEG enrichment analyses, we identified a series of enriched pathways and genes related to albinism, including melanogenesis (i.e., tyr, tyrp1b, kitb, kitlga, pmela, pmelb, mitfa, and mitfb) and xanthophore formation (i.e., pax3a, pax3b, pax7a, and sox10). In conclusion, this study not only enriches the research on fish pigmentation, but also has potential significance for the aquaculture and breeding of C. argus. Full article

Melanogenesis, the key biological process underlying skin hyperpigmentation, is tightly regulated by complex molecular signaling pathways. Consequently, targeting molecular regulators of this pathway is a crucial strategy for developing effective skin-whitening agents. Cannabinol (CBN), a minor cannabinoid, has been largely unexplored owing to its role in modulating skin pigmentation. This study aimed to elucidate the molecular mechanisms of CBN’s depigmenting effects using an α-MSH-induced B16F10 melanoma cell model. High-purity CBN was obtained via conversion of cannabidiol (CBD) and confirmed by HPLC. CBN significantly inhibited melanin synthesis and tyrosinase activity in a concentration-dependent manner, without any cytotoxicity. Furthermore, we investigated CBN’s impact on the melanogenesis signaling cascade. Our analysis revealed that CBN significantly downregulated the mRNA and protein levels of key melanogenic master regulators, including MITF, TYR, TYRP1, and TYRP2. Importantly, we also observed that CBN treatment selectively suppressed the protein phosphorylation of upstream signaling molecules such as p38 and JNK MAP kinases and NF-κB, while ERK phosphorylation remained unaffected. This finding indicates that its mechanism of action involves the selective modulation of pro-melanogenic signaling components. Collectively, these findings demonstrate that CBN effectively modulates the melanogenesis signaling pathway by targeting both upstream kinases and downstream melanogenic genes. These findings suggest that CBN holds great promise as a bioactive agent for skin-whitening applications and warrants further research to confirm its clinical efficacy and safety. Full article

Coat color is a crucial production trait for fur-bearing animals and significantly influences their economic value. The remarkable diversity of coat colors in rex rabbits not only provides a wide range of market options but also serves as an essential resource for investigating the genetic mechanisms underlying coat color formation. In this study, we conducted integrated transcriptomic and proteomic profiling of skin tissues from black and white Rex Rabbits, revealing the presence of 52 co-expressed genes/proteins. Proteomic analysis revealed a significant upregulation of PMEL (p = 0.030, FC = 2.194), while transcriptomic data indicated an even more pronounced upregulation (p = 0.028, FC = 35.279). Therefore, PMEL (Premelanosome Protein) may serve as a pivotal regulator of melanogenesis in Rex Rabbits. Our findings indicate that PMEL overexpression in melanocytes increases melanin content, promotes melanocyte proliferation, and enhances the expression of melanin-related genes (MITF, TYR, TYRP1, and GPNMB) while inhibiting melanocyte apoptosis. Conversely, PMEL knockdown significantly reduces melanin content, melanocyte proliferation, and the expression of melanin-related genes while promoting melanocyte apoptosis. These findings suggest that PMEL contributes to melanogenesis in Rex Rabbits. Full article

Percocypris pingi is an endangered protected fish species in China. Its albino variants exhibit growth retardation and physiological abnormalities. Understanding its albinism mechanism holds significant scientific importance for molecular breeding programs and disease model development. This study integrated transcriptomic and proteomic analyses, combined with histopathological and molecular biological techniques, to systematically compare molecular differences in skin tissues between albino and wild-type P. pingi, with a focus on elucidating the multidimensional regulatory mechanisms underlying skin albinism. Our findings suggest that albinism in P. pingi is synergistically driven by hyperactivation of ubiquitin-mediated proteolysis (which suppressed TYR/TYRP1 enzymatic activity and disrupted the pH homeostasis of melanosomes), and inhibition of calcium signaling (which impeded melanin transport). This discovery provides novel insights into the mechanisms of pigment loss in fish species and offers a valuable reference for molecular breeding of endangered species as well as research on pigmentation-related disorders. Full article