Search Results (798)

Skin hyperpigmentation caused by excessive melanin production has led to increasing interest in the development of effective anti-melanogenic agents. In this study, the anti-melanogenic effects and underlying mechanisms of nicotinamide mononucleotide (NMN) were investigated using α-MSH-induced B16F10 melanoma cells. NMN maintained over 80% cell viability at concentrations below 0.5% and significantly reduced α-MSH-induced melanin accumulation and melanin content. In addition, in situ tyrosinase assay demonstrated that NMN effectively suppressed intracellular melanogenesis. However, NMN did not exhibit direct inhibitory activity against mushroom tyrosinase. Molecular docking analysis further revealed that NMN did not directly interact with the catalytic copper-binding site of tyrosinase. Furthermore, tyrosinase zymography and Western blot analyses demonstrated that NMN suppressed melanogenesis primarily through downregulation of tyrosinase protein expression rather than direct inhibition of tyrosinase catalytic activity. Collectively, these findings suggest that NMN suppresses melanogenesis through regulation of melanogenic signaling pathways, indicating its potential utility for hyperpigmentation-related applications. Full article

Excessive melanin accumulation induced by UV exposure and hormonal changes poses significant challenges to skin health, necessitating safe and effective tyrosinase inhibitors. Pearl and nacre powder have long been utilized in traditional Chinese medicine for skin whitening. Our previous study identified a tyrosinase inhibitory peptide (Ala-His-Tyr-Tyr-Asp) from Pinctada martensii nacre in silico; however, chemical modification strategies for enhancing bioactive peptide efficacy remain underexplored. The present study investigated the structure-activity relationship of NP-TIP-1 (Tyrosinase Inhibitory Peptide of Nacre Powder-1) through three chemical modifications (C-terminal amidation, N-terminal acetylation, and N-terminal palmitoylation). C-terminal amidation significantly improved tyrosinase inhibitory potency, reducing the IC50 value from 2.012 ± 0.088 mM to 0.979 ± 0.028 mM, while retaining thermal stability and copper ion chelating capacity comparable to the native peptide. In B16F10 melanoma cells, NP-TIP-1-NH₂ (C-terminally amidated NP-TIP-1) exhibited no cytotoxicity at concentrations up to 600 μM and concentration-dependently suppressed intracellular tyrosinase activity and melanin content. Mechanistic investigation revealed that NP-TIP-1-NH₂ treatment downregulates the mRNA and protein expression of TYR and TRP-1 without affecting MITF (Microphthalmia-associated Transcription Factor) or TRP-2, suggesting a potential regulatory mechanism independent of MITF-mediated transcriptional control. Non-targeted metabolomics further identified nucleotide metabolism, purine metabolism, and glycine/serine/threonine metabolism as the most significantly perturbed pathways, with cytosine and GMP downregulated while guanosine and guanine were upregulated. This study establishes NP-TIP-1-NH₂ as a promising candidate for multifunctional food preservatives and nutraceuticals, providing a strategic framework for C-terminal amidation as a structure-activity optimization approach for marine-derived anti-melanogenic peptides. Full article

The field of cosmetic science is rapidly evolving due to advances in skin biology research and increasing demand for evidence-based, personalized skincare solutions. A key aspect of this progress is the targeted modulation of biological macromolecules involved in skin aging, pigmentation, inflammation, and tissue regeneration. This review highlights major molecular targets in modern cosmetic research, focusing on telomerase, histone deacetylases (particularly sirtuins), matrix metalloproteinases, antioxidant enzymes, CD44 receptor, tyrosinase, microphthalmia-associated transcription factor, and melanocortin receptors, all of which regulate processes such as DNA repair, gene expression, extracellular matrix remodeling, and melanogenesis. Recent findings indicate that natural and synthetic compounds can effectively modulate these targets, supporting anti-aging and depigmenting strategies. Telomerase activators and sirtuin modulators show potential in maintaining cellular homeostasis and delaying skin aging. In pigmentation research, the transition from mushroom to human tyrosinase assays has enabled development of more selective inhibitors, including thiamidol. The review also addresses molecular targets relevant to inflammatory skin disorders, scars, and skin atrophy. Advances in molecular and biotechnological methods are expected to improve mechanistic understanding and support the rational design of safer, more effective next-generation cosmetic ingredients and formulations. Full article

Skin aging is a major consideration regarding cosmetic skin care. The cosmetic field is seeking new active ingredients able to slow down the appearance of signs of age. Some lichens and more specifically the genus Cetraria s. str. presents an interest as a source of active molecules because it is already being used in traditional and modern medicines. To better evaluate the potential of C. islandica as anti-aging skin care, we investigated some key aspects to protect skin from external aggression and to avoid skin alteration, which would exacerbate signs of age. Among them, our results reveal (i) antioxidant capacities; (ii) anti-inflammatory properties on human keratinocytes once stimulated, as shown by a decrease in IL-6, IL-8, CXCL9, CXCL10, and CCL5; (iii) a downregulation of MT1-MMP, which corresponds to decreased tissue remodeling; and (iv) an inhibition of human tyrosinase, which could correct the appearance over time of age-related skin spots. Altogether, these results highlight the potential use of C. islandica in anti-aging skin care. Full article

Background/Objectives: Vitis vinifera is a rich source of polyphenolic compounds that are known for their benefits on skin health, including antioxidant, anti-inflammatory, and photoprotective effects. Red wines have shown a positive impact on cardiovascular disease, diabetes, and cancer prevention; however, evidence regarding their effects on skin biology remains scarce. This study evaluated red wine concentrates obtained from Cabernet Sauvignon and Merlot varieties, selected based on their previously demonstrated biological activities, to identify the samples with the highest potential for skin health applications by assessing their inhibitory activity against skin-related enzymes (tyrosinase, elastase, and collagenase), along with their effects on HaCaT cells, including cytotoxic, antioxidant, anti-inflammatory, and wound healing activities. Methods: Enzyme inhibition studies were based on spectrophotometric methods; the MTT and CV assays were carried out to test the cytotoxicity, and the DCFH-DA assay was employed to evaluate the antioxidant activity of the wine concentrates; wound healing potential was examined by the cell scratch assay, and anti-inflammatory activity was investigated using ELISA and qPCR analyses. PCA of the samples and their biological activity was performed as well. Results: Examined red wine concentrates exhibited significant enzyme inhibitory activity and showed no cytotoxicity on HaCaT cells up to the concentration of 50 μg/mL; the samples stimulated cell migration, inhibited intracellular ROS production in AAPH-stressed keratinocytes, and selectively modulated TNF-α-induced inflammatory responses, reducing IL-8 secretion while enhancing certain cytokine transcripts, underscoring the complexity of their bioactive effects. Conclusions: Red wine concentrates showed significant potential as skin-beneficial agents, demonstrating strong antiaging, marked cellular antioxidant effects and wound healing activity when applied at non-cytotoxic concentrations. Multivariate analysis revealed distinct bioactivity profiles among the wine concentrates. Full article

The development of effective cosmetic formulations containing L-ascorbic acid is hindered by its rapid degradation and poor skin permeation. To address these limitations, this study identified an optimal synergistic antioxidant combination to enhance L-ascorbic acid efficacy and encapsulated it within a niosomes to improve stability and skin retention. Among various ratios evaluated via DPPH assays, a 1:1:2:2 combination of L-ascorbic acid, alpha-tocopherol, ferulic acid, and ergothioneine (Mix D) exhibited the highest synergism. Subsequent FRAP, anti-tyrosinase, and anti-aging inhibition assays confirmed that Mix D contributed to skin-brightening and anti-aging efficacy. Consequently, Mix D was encapsulated into niosomes (NI3-3A), initially showing a vesicle size of 130.67 nm and a PDI of 0.11, and an entrapment efficiency of 70.63%. NI3-3A provided exceptional chemical protection, limiting L-ascorbic acid degradation to 25.06% and maintaining an entrapment efficiency of 63.93% over 90 days due to its robust bilayer structure. Furthermore, it exhibited remarkable physicochemical stability, with a vesicle size of 140.27 nm and PDI of 0.09 after 90 days, while achieving a skin retention of 56.91% significantly higher than the unencapsulated solution (11.32%). In conclusion, this niosomal formulation successfully overcomes the stability limitations of L-ascorbic acid, offering a promising active ingredient for the development of advanced skin-brightening and anti-aging topical products. Full article

Nelumbo nucifera Gaertn. is a rich source of bioactive compounds, and has been extensively investigated for its antioxidant and anti-inflammatory properties. However, despite its broad pharmacological potential, detailed molecular-level insights into the interactions of its phenolic and flavonoid constituents with key skin-aging-related enzymes remain limited. Therefore, this study employed an integrated in silico and in vitro approach to systematically evaluate the anti-aging potential of phenolic and flavonoid compounds derived from N. nucifera. Molecular docking was performed to investigate their binding interactions with tyrosinase, elastase, and collagenase. Compounds exhibiting the most promising inhibitory profiles were further subjected to molecular dynamics (MD) simulations for 100 ns and density functional theory (DFT) analyses at the B3LYP/6-31G(d,p) level of theory to elucidate their structural stability and electronic properties. The computational results revealed favorable binding affinities, stable complex formation, and electrostatic features supporting hydrogen bond interactions. In vitro enzyme inhibition assays demonstrated that hesperidin exhibited inhibitory activity against tyrosinase, collagenase, and elastase, with IC₅₀ values of 3.43 mM, 2.26 mM, and 0.55 mM, respectively. Kojic acid was used as a positive control for tyrosinase, while epigallocatechin gallate (EGCG) was used as a positive control for both collagenase and elastase. Additionally, hesperidin exhibited enzyme-inhibitory activity and preliminary intrinsic UV absorption. This compound warrants further investigation, specifically regarding its stability and performance within standardized cosmeceutical formulations. Full article

Ganoderma lucidum is a medicinal mushroom widely recognized as a source of bioactive metabolites, particularly triterpenoids. Although most studies have focused on fruiting bodies and spores, the potential of cultured mycelial biomass as a source of functional secondary metabolites remains less explored. In this study, we isolated and characterized polycarpol from the mycelia of G. lucidum and evaluated its anti-melanogenic activity in B16F10 murine melanoma cells. Dried mycelia obtained after liquid culture were extracted with 70% ethanol, partitioned with ethyl acetate, and purified by repeated chromatographic separation. The isolated compound was identified as polycarpol by LC–ESI–MS, HR-MS/MS, and NMR spectroscopy, together with comparison with previously reported spectroscopic data. The anti-melanogenic activity of polycarpol was evaluated in α-MSH-stimulated B16F10 murine melanoma cells, a commonly used cellular model of melanogenesis. Polycarpol reduced α-melanocyte-stimulating hormone-induced cellular tyrosinase activity and melanin production at concentrations that did not markedly affect cell viability. Notably, 2 μg/mL (4.54 μM) polycarpol showed a melanin-inhibitory effect comparable to that of arbutin. Western blot analysis showed that polycarpol decreased the expression of microphthalmia-associated transcription factor, tyrosinase, and tyrosinase-related protein-1. In addition, polycarpol suppressed CREB phosphorylation and modulated the MAPK signaling pathways. These findings suggest that polycarpol inhibits melanogenesis through regulation of MITF-associated melanogenic signaling. Overall, this study demonstrates that cultured G. lucidum mycelia can produce anti-melanogenic triterpenoids and highlights cultured mycelial biomass as a controllable fungal material for exploring anti-melanogenic triterpenoids, although further optimization is required to improve production efficiency. Full article

The genus Dalea (Fabaceae) comprises approximately 188 recognized species distributed mainly in arid and semi-arid regions of the American continent, where several species have been traditionally used in folk medicine for the treatment of gastrointestinal disorders, infections, inflammation, and other ailments. In recent years, Dalea species have attracted considerable scientific interest due to their remarkable diversity of secondary metabolites, particularly prenylated flavonoids, isoflavonoids, rotenoids, chalcones, stilbenes, and terpenoid-rich essential oils. Among these compounds, prenylated and geranylated flavonoids represent some of the most characteristic metabolites of the genus and are strongly associated with its reported biological activities. This review summarizes current knowledge regarding the taxonomy, distribution, traditional uses, phytochemical profile, pharmacological activities, and toxicological aspects of the genus Dalea. Although only about 19 species (approximately 10% of currently recognized species) have been subjected to phytochemical investigation, substantial knowledge gaps remain within the genus. Special emphasis is placed on prenylated phenolic compounds because of their structural diversity and broad spectrum of biological activities, including antibacterial, antifungal, antiparasitic, anti-inflammatory, neuroprotective, anticancer, anti-tyrosinase, and xanthine-oxidase-inhibitory effects. Despite promising pharmacological findings, most available evidence remains limited to in vitro evaluations, with relatively few studies including in vivo validation or mechanistic investigations. Furthermore, important challenges remain regarding toxicity, pharmacokinetics, metabolomic characterization, and sustainable production of bioactive metabolites. Overall, the available evidence highlights Dalea as a valuable source of bioactive compounds with potential pharmaceutical applications and supports the need for further interdisciplinary research focused on drug discovery and development. Full article

Despite the well-established bioactivity of Salvia verticillata L. aerial parts, their roots represent an unexplored plant matrix. In this study, root extracts obtained by ethnopharmacological (EE), maceration (ME), and ultrasound-assisted (UE) extraction were examined. Ultrasound-assisted extraction was optimized using response surface methodology (RSM, CCD) to maximize total phenolic content (TPC) and rosmarinic acid (RA), and the optimized extract was compared with EE and ME. All extracts exhibited high levels of total phenolics, flavonoids, and phenolic acids, while RA was the dominant compound according to HPLC analysis (96.67–137.47 mg g⁻¹ d.e.). UE yielded the highest TPC and exhibited the strongest antioxidant activity in most of the applied assays. All extracts exhibited concentration-dependent tyrosinase inhibitory activity, with UE and EE showing the strongest effects. Moderate antibacterial activity, particularly against Gram-positive strains, and limited antifungal effects were observed. Strong COX-1 inhibition (>70% at 50 μg/mL) confirmed the anti-inflammatory potential of the extracts, whereas slight COX-2 inhibition was observed. UE exhibited moderate cytotoxic activity against A431, SVT2, and HaCaT cells. These findings identify S. verticillata roots as a promising source of rosmarinic acid-rich extracts and point out the importance of the extraction procedure to tailor the biological activity of the extract. Full article

Skin photoaging is primarily induced by ultraviolet (UV) radiation and is accompanied by extracellular matrix (ECM) degradation, abnormal pigmentation, and loss of skin elasticity. Excessive melanin synthesis represents a key cause of pigmentary skin disorders. Natural polyphenols with dual skin-whitening and anti-photoaging activities have attracted increasing attention as cosmetic ingredients. This study examined the effects of polyphenol-enriched fraction from the brown alga Sargassum fusiforme (SFP). Zebrafish embryos and human melanoma A375 cells were used to evaluate the depigmenting efficacy of SFP, while UVA-induced human dermal fibroblasts (HDFs) were employed to assess its anti-photoaging activity. SFP significantly decreased melanin levels in both models in a dose-dependent and reversible manner by suppressing tyrosinase activity. In terms of anti-photoaging effects, SFP markedly suppressed UVA-induced matrix metalloproteinases (MMPs) expression and elevated key ECM components, including type I collagen, elastin, and hyaluronic acid. In conclusion, SFP exerts dual beneficial effects by attenuating melanogenesis via tyrosinase inhibition and alleviating photoaging damage by suppressing MMPs to protect ECM. These results provide a scientific foundation for the use of SFP as a dual-purpose natural cosmetic ingredient with significant potential in the cosmetics sector. Full article

A key factor that regulates melanogenesis is the activity of tyrosinase, and inhibitors of this enzyme are used as skin-whitening and lightening agents in the skincare and cosmetics industries. The methanolic extract from male inflorescences of Artocarpus altilis (Parkinson) Fosberg (breadfruit) was investigated for its bioactivities which are important for the skincare industry, including anti-tyrosinase activity. Bioassay-guided fractionation led to the isolation of a geranylated dihydrochalcone, 2-Geranyl-2’,3,4,4’-tetrahydroxydihydrochalcone (hereinafter referred to as Artochalcone), present at 1.64% of the inflorescence dry weight. Its structure was determined by a combination of 1D and 2D-NMR and HR-ESI-MS analysis. Artochalcone was found to inhibit tyrosinase with an IC₅₀ value of 28.4 μM, making it sixteen times more effective than the leading commercial skin-whitening agent, arbutin. In addition, Artochalcone displayed significant antioxidant activity determined by 2,2-diphenyl-1-picrylhydrazyl (IC₅₀ = 20.4 μM) and nitric oxide scavenging assays (IC₅₀ = 20.7 μM). Full article

Valorizing agricultural byproducts into functional ingredients is highly desirable. Herein, plant-derived nanovesicles (PDNVs) from Paris polyphylla stems/leaves (SL-EXO) exhibited potent anti-melanogenic properties, whereas root-derived PDNVs were ineffective. In vitro, SL-EXO achieved 92.66% cell-free tyrosinase inhibition, while α-arbutin was 49.78%. In vivo, SL-EXO ameliorated the pigmentation-driving oxidative/senescent microenvironment in zebrafish and reduced macroscopic melanin by ~66%. Crucially, SL-EXO reversed α-MSH-induced hyperpigmentation in B16F10 cells while maintaining excellent biocompatibility up to 0.15 mg/mL, displaying a vastly superior safety margin compared to α-arbutin (which induced cytotoxicity at 0.075 mg/mL). To decode this, multi-omics profiling revealed that SL-EXO utilizes a chloroplast-derived biomimetic lipid architecture (enriched in MGDG/DGDG) to efficiently deliver potent flavonoid payloads. Molecular docking demonstrated exceptional predictive structural affinities (binding energies up to −10.9 kcal/mol) between these phytochemicals and AKT1. Finally, pharmacological rescue assays validated that SL-EXO arrests melanogenesis by targeting the AKT1 pathway, thereby downregulating the p-AKT/p-GSK3/MITF signaling cascade and silencing melanogenic genes. This study establishes a rigorous multi-omics paradigm for upcycling botanical wastes into exceptionally safe and efficacious natural anti-melanogenic nanotherapeutics. Full article

Hypericum perforatum L. olive-oil macerate is a traditional topical remedy whose wound-healing efficacy is well documented, yet the phytochemical and mechanistic basis of its cosmetic-relevant activity remains poorly defined. This study provides an integrated experimental and in silico characterization of a traditionally prepared macerate of defined origin. The fatty acid composition, oxidative-stability indices, total phenolic and flavonoid contents, naphthodianthrone level, antioxidant capacity, and tyrosinase inhibition were determined, and the principal constituents were examined by molecular docking and in silico skin-permeation and toxicity profiling. The olive-oil matrix was oleic acid-dominated (73.9%) and oxidatively stable (iodine value 86.0; oxidizability index, COX, 1.84), while the macerate showed modest phenolic ($36.84 \mathsf{\mu }$g pyrocatechol equivalents, PCE/mg) and naphthodianthrone (0.044 mg/mL hypericin equivalents) contents. It showed limited antioxidant activity but moderate tyrosinase inhibition (38.75% at $200 \mathsf{\mu }$g/mL). Docking revealed that, despite high affinity scores, the naphthodianthrones lay 7–9 Å from the catalytic copper centre (an artefact of the scoring function), whereas fatty acids accessed the active site more closely, implicating the matrix in the observed activity. In silico profiling indicated that the photoactive naphthodianthrones are largely retained at the skin surface. These findings link this centuries-old preparation to a mechanistically informed understanding of its cosmetic potential. Full article

Background/Objectives: Dysregulated melanogenesis underpins numerous hyperpigmentation disorders. Gancidin W, a naturally occurring diketopiperazine with diverse biological activities, has attracted interest as a potential bioactive compound; however, its role in melanogenesis remains largely unexplored. This study aimed to evaluate the anti-melanogenic potential of Gancidin W through an integrated experimental and computational approach. Methods: Network pharmacology analysis was performed to investigate the potential molecular mechanisms of Gancidin W against hyperpigmentation. The cellular effects of Gancidin W were evaluated in α-MSH-stimulated B16F10 melanoma cells by assessing intracellular tyrosinase activity, melanin content, and cytotoxicity. Furthermore, density functional theory (DFT) calculations, molecular dynamics (MD) simulations, MM/GBSA binding free-energy analysis, and relative binding free-energy (RBFE) calculations were conducted to investigate the molecular interactions of Gancidin W and its structurally related analogue Maculosin with human tyrosinase-related protein 1 (hTYRP1). Results: Network pharmacology analysis predicted potential targets and signaling pathways involved in melanogenesis regulation. Gancidin W reduced intracellular tyrosinase activity by 34.54% and melanin content by 25.09% without cytotoxic effects. Multiscale computational analyses demonstrated stable interactions of Gancidin W within the hTYRP1 active site and favorable binding energetics (ΔG_bind = −28.77 ± 0.75 kcal/mol). Compared with Maculosin, Gancidin W exhibited a more favorable binding profile, as supported by MM/GBSA and RBFE analyses, consistent with the inhibitory effects observed in the cellular assays. Conclusions: Gancidin W exhibits anti-melanogenic potential, and multiscale computational analyses provide molecular insights into its interaction with hTYRP1. These findings support further investigation of Gancidin W as a potential natural depigmenting agent for hyperpigmentation-related disorders. Full article