Search Results (376)

Ultraviolet B (UVB) radiation is a key factor in the overproduction of melanin in the skin. Melanocytes produce melanin through melanogenesis to protect the skin from UVB radiation-induced damage. However, excessive melanogenesis can lead to hyperpigmentation and increase the risk of malignant melanoma. Tyrosinase is the rate-limiting enzyme in melanogenesis; it catalyzes the oxidation of tyrosine to 3,4-dihydroxy-L-phenylalanine and subsequently to dopaquinone. Thus, inhibiting tyrosinase is a promising strategy for preventing melanogenesis and skin hyperpigmentation. White mulberry (Morus alba L.) is rich in antioxidants, and mulberry fruit extracts have been used as cosmetic skin-lightening agents. However, data on the capacity of mulberry fruit extracts to inhibit tyrosinase under UVB radiation-induced melanogenic conditions remain scarce, especially in an in vivo model. In this study, we evaluated the effects of a mulberry crude extract (MCE) on UVB radiation-induced melanogenesis in B16F10 melanoma cells and zebrafish embryos. The MCE significantly reduced tyrosinase activity and melanogenesis in a dose-dependent manner without inducing cytotoxicity. These effects are likely attributable to the antioxidant constituents of the extract. Our findings highlight the potential of this MCE as an effective tyrosinase inhibitor for the prevention of UVB radiation-induced skin hyperpigmentation. Full article

Skin aging is a natural biological process that can be accelerated by free radical induction, leading to a reduction in skin elasticity and the formation of wrinkles due to the depletion of elastin. Eugenia uniflora (dewandaru) is a promising plant believed to possess anti-aging properties, primarily attributed to its major constituents, myricitrin and quercetin. This study aimed to investigate the anti-elastase and antioxidant properties of Eugenia uniflora stem bark, ripe fruit, and seed extracts. Extracts were obtained using an ultrasound-assisted extraction (UAE) method with 70% ethanol. Quantitative phytochemical analysis involved measuring the total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity. Bioactive constituents were identified using LC-MS analysis, and their interactions with target enzymes were further evaluated through in silico molecular docking. The results demonstrated that the E. uniflora seed extract exhibited the highest antioxidant activity, with an IC₅₀ of 5.23 µg/mL (DPPH assay) and a FRAP value of 3233.32 µmol FeSO₄/g. Furthermore, the ethanolic seed extract showed significant anti-elastase activity with an IC₅₀ of 114.14 µg/mL. Molecular docking predicted strong potential for several compounds as pancreatic elastase inhibitors, including 5-phenylvaleric acid, 2-(3-phenylpropyl)phenol, n-amylbenzene, 2-aminoadipic acid, and traumatin, each showing a prediction activity (PA) value exceeding 0.6. Notably, these compounds also exhibited inhibitory activity against tyrosinase. These findings collectively underscore the significant promise of E. uniflora seed extract as a novel and natural candidate for pharmacocosmeceutical product development, particularly for anti-aging applications. Full article

The current study investigates the chemical profiling, antioxidant activities, and enzyme inhibitory and cytotoxic potential of the water and methanolic extracts of different parts (flower, leaf, and bulb) of Muscari armeniacum. Chemical profiling was performed using UHPLC-MS/MS. At the same time, different in vitro assays were employed to support the results for antioxidant potential, such as DPPH, ABTS, FRAP, CUPRAC, metal chelation, and PBD, along with the measurement of total phenolic and flavonoid contents. Enzyme inhibition was investigated for cholinesterase (AChE and BChE), α-amylase, α-glucosidase, and tyrosinase enzymes. Additionally, the relative expression of NRF2, HMOX1, and YGS was evaluated by qPCR. LC-MS/MS analysis indicated the presence of some significant compounds, including apigenin, muscaroside, hyacinthacine A, B, and C, and luteolin. According to the results, the highest TPC and TFC were obtained with both extracts of the leaves, followed by the water extract (flower) and methanolic extract of the bulb. In contrast, the methanolic extract from the bulb exhibited the highest antioxidant potential using DPPH, ABTS, CUPRAC, and FRAP, followed by the extracts of leaves. In contrast, the leaf extracts had the highest values for the PBD assay and maximum chelation ability compared to other tested extracts. According to the enzyme inhibition studies, the methanolic extract from the bulb appeared to be the most potent inhibitor for all the tested enzymes, with the highest values obtained for AChE (1.96 ± 0.05), BChE (2.19 ± 0.33), α-amylase (0.56 ± 0.02), α-glucosidase (2.32 ± 0.01), and tyrosinase (57.19 ± 0.87). Interestingly, the water extract from the bulb did not inhibit most of the tested enzymes. The relative expression of NRF2 based on qPCR analysis was considerably greater in the flower methanol extract compared to the other extracts (p < 0.05). The relative expression of HMOX1 was stable in all the extracts, whereas YGS expression remained stable in all the treatments and had no statistical differences. The current results indicate that the components of M. armeniacum (leaves, flowers, and bulb) may be a useful source of natural bioactive compounds that are effective against oxidative stress-related conditions, including hyperglycemia, skin disorders, and neurodegenerative diseases. Complementary in silico approaches, including molecular docking, dynamics simulations, and transcription factor (TF) network analysis for NFE2L2, supported the experimental findings and suggested possible multi-target interactions for the selected compounds. Full article

Tetrastigma erubescens, a native medicinal plant of Vietnam, has long been used in folk medicine to manage various diseases, including skin-related issues. However, limited research has been conducted on this herb’s bioactivities and chemical composition. This study aims to investigate the chemical constituents and evaluate the anti-tyrosinase activity and UV-A/UV-B absorption capacity of T. erubescens extracts, highlighting their potential as natural sources for skin-whitening and sun protection agents. In vitro assays demonstrated that the ethyl acetate (EA) extract of T. erubescens exhibited a significant UV-A and UV-B absorption capacity. Notably, this extract showed a strong anti-tyrosinase activity for the first time, with a maximum inhibition rate of 99.2% and an IC₅₀ value of 70.3 µg/mL. Based on the UHPLC and GCMS analysis, phenolic compounds (1–9) and ten volatile constituents (10–19) were identified in the EA extract of T. erubescens. Of these, almost all volatiles and some phenolics were reported for the first time in this genus. The molecular docking analysis revealed that all identified phytochemicals showed a comparable or greater binding affinity to both mushroom tyrosinase (docking scores: from −7.5 to −14.1 kcal/mol) and human tyrosinase (from −6.7 to −14.8 kcal/mol) than kojic acid (−8.7 and −8.6 kcal/mol, respectively). In addition, these identified compounds showed favorable drug-like properties and low toxicity risks via ADMET prediction and Lipinski’s Rule of Five analyses. The results obtained in this work suggest that the EA extract of T. erubescens is a promising natural source of bioactive compounds for cosmetic applications, particularly in whitening and sun protection formulations. Full article

This study investigated the potential cosmetic properties of the ethyl acetate (EtOAc) fraction obtained from the roots of Astilboides tabularis (Hemsl.) Engl., focusing on skin-whitening, antiwrinkle, and moisturizing effects using cell-based assays and three-dimensional (3D) artificial skin models (Neoderm-ED and Neoderm-ME). The EtOAc fraction showed significant dose-dependent inhibitory activity against tyrosinase (TYR) (72.0% inhibition at 50 µg/mL), comparable to that of kojic acid. In α-melanocyte-stimulating hormone (α-MSH)-stimulated Neoderm-ME artificial skin containing melanocytes, the EtOAc fraction reduced melanin synthesis at concentrations of 50 and 75 µg/mL and decreased melanogenesis-related gene expression, including TYR, microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1) and TRP-2. In the antiwrinkle assays, the EtOAc fraction effectively inhibited elastase activity (41.5% inhibition at 10 µg/mL), exceeding the efficacy of ursolic acid. In the Neoderm-ED artificial skin model, the EtOAc fraction reversed structural damage induced by particulate matter (PM10), restoring epidermal thickness and dermal density. This improvement was supported by the increased expression of skin barrier and antiwrinkle genes, including filaggrin, hyaluronic acid synthase-1 (HAS-1), HAS-2, aquaporin-3 (AQP-3), collagen type I alpha 1 chain (COL1A1), elastin, tissue inhibitor of metalloproteinases-1 (TIMP-1), and TIMP-2, as well as decreased expression of matrix metalloproteinases (MMP-1, MMP-3, and MMP-9). Our results indicate that the EtOAc fraction from A. tabularis root has considerable potential as a multifunctional cosmetic. Full article

The growing demand for natural anti-aging ingredients necessitates scientific validation of traditional cosmetic materials. Multani Mitti (MM), a clay widely used in South Asian traditional skincare, lacks comprehensive chemical and biological characterization. This study employed a multi-analytical approach to investigate MM’s anti-aging potential through chemical analysis, enzyme inhibition studies, and in silico evaluations. Five commercial MM samples were pooled and analyzed using instrumental neutron activation analysis (INAA) and Gas Chromatography–Mass Spectrometry (GC-MS). INAA revealed silicon as the predominant inorganic constituent (169.3742 mg/g), while GC-MS identified 13 bioactive compounds, with Beta-sitosterol (15.45% area), Docosanamide (12.36% area), and Cyclohexasiloxane (9.80% area) being the most abundant. MM demonstrated significant enzyme inhibition against key aging-related enzymes, with notably strong effects on hyaluronidase (IC₅₀: 18 μg/mL) and tyrosinase (IC₅₀: 27 μg/mL), outperforming standard inhibitors. The antioxidant activity showed moderate effectiveness (IC₅₀: 31.938 μg/mL) compared to ascorbic acid (IC₅₀: 8.5 μg/mL). Molecular docking studies of identified compounds against hyaluronidase (PDB: 1FCV) and tyrosinase (PDB: 3NQ1) revealed Beta-sitosterol and Benzyl-piperazine-carboxamide as the most promising candidates, showing strong binding affinities (−8.5 and −8.6 kcal/mol, respectively) and favorable ADMET profiles. This comprehensive characterization provides the first scientific evidence supporting MM’s traditional use in skincare and identifies specific compounds that may contribute to its anti-aging properties, warranting further investigation for modern cosmetic applications. Full article

Modern dermocosmetics combine the effectiveness of active substances with the benefits of percutaneous penetration enhancers to address skin issues such as hyperpigmentation. In this study, three bioactive tripeptides (with amino acid sequences CSF, CVL, and CSN) with previously confirmed tyrosinase inhibition activity were synthesized using the solid-phase synthesis method. The structures of the obtained peptides were determined. In addition, elastase in silico and in vitro inhibition assays were carried out. The tripeptides were subsequently encapsulated into liposomes, for which key physicochemical parameters were determined, including size, zeta potential, and encapsulation efficiency. The average diameter of the prepared liposomes was approximately 100 nm across all samples. The prepared carriers were found to be stable and exhibited no cytotoxicity toward reconstructed human epidermis cells. The peptides achieved an encapsulation efficiency of approximately 20–30%, with no significant differences observed between the cationic and anionic vesicles. Liposomes containing the CSF tripeptide, which showed the strongest tyrosinase-inhibiting effect, did not transport the peptide through the human skin in an ex vivo assay to permit quantification in the receptor solution, but facilitated penetration and retention of the tripeptide within the epidermis (4.65 ± 1.81 μg/cm²). These findings suggest that the prepared liposomes may serve as valuable carriers of bioactive tripeptides in anti-aging cosmetics. Full article

Pentagalloylglucose (PGG) is a powerful antioxidant and a naturally derived polyphenolic compound present in tannins. In this study, we investigated the ability of PGG to selectively inhibit hyperpigmentation through the regulation of melanogenesis in melanocytes. PGG inhibited melanin production in α-melanocyte-stimulating hormone (α-MSH)-induced B16F10 melanoma cells. Furthermore, PGG suppressed the expression of melanin synthesis enzymes, such as tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. The mRNA and protein expression of the microphthalmia-associated transcription factor, which is involved in the mechanism of melanogenesis, was also reduced by PGG, and this effect was induced via PKA/CREB and MAPK phosphorylation. These results suggest that PGG inhibits α-MSH-induced melanin production by regulating the PKA/CREB/MAPK signaling pathway, indicating that natural compounds can serve as inhibitors of melanogenesis. Full article

Skin hyperpigmentation disorders, such as melasma, are linked to excessive melanin production, primarily regulated by the enzyme tyrosinase (TYR). While current inhibitors like kojic acid (KA) are effective, they often cause adverse side effects, driving the search for safer andnatural alternatives. This study evaluated the TYR inhibitory potential of bioactive-rich extracts from acorn, cocoa, cork, and eucalyptus, extracted using hydroethanolic (HE) and natural deep eutectic solvents (NADES), and explored the enhancement of their bioactivity through laccase-assisted polymerization. NADES significantly improved extraction yields and preserved bioactive compounds, with cocoa extracts showing the highest TYR inhibition. Laccase-mediated polymerization further enhanced TYR inhibitory activity, particularly of NADES extracts, suggesting a more effective and sustainable approach for skincare applications. The results highlight the potential of combining green chemistry principles with enzymatic catalysis to develop eco-friendly and efficient treatments for hyperpigmentation disorders, offering a promising alternative to conventional methods. Full article

Azelaic acid (AZA), an aliphatic dicarboxylic acid (HOOC-(CH2)₇-COOH), is widely used in dermatology. It functions as an inhibitor of tyrosinase, mitochondrial respiratory chain enzymes, and DNA synthesis, while also scavenging free radicals and reducing reactive oxygen species (ROS) production by neutrophils. AZA has demonstrated anti-proliferative and cytotoxic effects on various cancer cells. However, its therapeutic potential in acute myeloid leukemia (AML) remains largely unexplored. AML is a complex hematologic malignancy characterized by the clonal transformation of hematopoietic precursor cells, involving chromosomal rearrangements and multiple gene mutations. The disease is associated with poor prognosis and high relapse rates, primarily due to its propensity to develop resistance to treatment. Recent studies indicate that AZA suppresses AML cell proliferation by inducing apoptosis and arresting the cell cycle at the G1 phase, with minimal cytotoxic effects on healthy cells. Additionally, AZA exerts antileukemic activity by modulating the ROS signaling pathway, enhancing the total antioxidant capacity in both AML cell lines and patient-derived cells. AZA also sensitizes AML cells to Ara-C chemotherapy. In vivo, AZA has been shown to reduce leukemic spleen infiltration and extend survival. As our understanding of AML biology progresses, the development of new molecularly targeted agents, in combination with traditional chemotherapy, offers the potential for improved treatment outcomes. This review aims to provide a comprehensive synthesis of preclinical evidence on the therapeutic potential of AZA in AML, consolidating current knowledge and identifying future directions for its clinical application. Full article

The whitening potential of natural products is commonly assessed through spectrophotometric assays that colorimetrically measure the inhibitory effects on tyrosinase, a key enzyme in pigment formation. However, these assays fail to provide evidence about the input of individual components into the total activity of a mixture like plant extracts. This study introduced chromatographic methods to identify active natural products without isolating them from their mixtures. In this study, various plant extracts of differing polarities (EtOH, 50% EtOH, and HOH) from species growing in the Lubelskie region of Poland were evaluated for their ability to inhibit tyrosinase. The most active extract identified through spectrophotometric assays was a 50% EtOH extract from Matricaria recutita L. (Chamomilla recutita (L.) Rauschert). Subsequent HPLC-MS analysis allowed for the identification of several active compounds from different classes, including organic acids, glycosylated phenolics, and phenolic acids that interacted with the enzyme. The bioactivity of individual components was confirmed through classical spectrophotometric assays, highlighting ferulic acid (IC₅₀ = 0.484 µM), quinic acid (IC₅₀ = 22.90 µM), and citric acid (IC₅₀ = 24.18 µM) as three representatives of different classes of molecules with inhibitory potential. Furthermore, the whitening capacity of the chamomile extract was investigated in a zebrafish model, demonstrating effective pigmentation inhibition in Danio rerio larvae and validating the proposed chromatographic approach. Full article

Hyperpigmentation can be prevented by regulating melanin synthesis through tyrosinase inhibition. As such, tyrosinase inhibitors like arbutin, kojic acid, and hydroquinone are commonly used for skin lightening. Recent studies suggest that certain pyrazole derivatives with tyrosinase activity may also have anticancer potential by influencing melanocyte transformation and tumor progression, positioning them as promising candidates for both cosmetic and therapeutic uses. The aim of this study was to evaluate the tyrosinase inhibitory activity of carbothioamidopyrazole derivatives. Inhibition was determined using the Dixon method, leveraging in silico molecular docking and circular dichroism (CD) spectroscopy to analyze fluorescence quenching. Carbothioamidopyrazole derivatives at the C-3 and C-5 positions in the pyrazole ring may be effective alternatives to traditional skin-lightening agents. These derivatives can induce structural changes in tyrosinase, thus altering its activity, and influence melanocyte transformation. Their dual action as tyrosinase inhibitors and potential anticancer agents makes them valuable for future research. Two compounds exhibited stronger inhibitory activity than kojic acid. Molecular docking suggests that these derivatives may block tyrosinase activity by preventing substrate access to its active site. These results underscore the potential of pyrazole derivatives for both cosmetic and therapeutic applications. Full article

The 2,4-dihydroxyphenyl group is commonly present in the chemical structures of potent tyrosinase inhibitors. Based on this observation, a series of 6-(substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole compounds 1–13 were designed and synthesized as potential tyrosinase inhibitors. Among these, compounds 5 and 9 strongly inhibited mushroom tyrosinase activity. Particularly, compound 9 exhibited nanomolar IC₅₀ values regardless of the substrate used, whereas kojic acid yielded IC₅₀ values of 15.99–26.18 μM. Kinetic studies on mushroom tyrosinase revealed that compounds 5 and 9 competitively inhibited tyrosinase activity, findings further corroborated by in silico docking analysis. In B16F10 cell-based experiments, both compounds effectively inhibited the cellular tyrosinase activity and melanin formation. These inhibitory effects were confirmed through in situ cellular tyrosinase activity assays. Compound 9 exhibited strong antioxidant activity by scavenging radicals, suggesting that its ability to reduce melanin production may be attributed to a combination of its antioxidant and tyrosinase inhibitory properties. Additionally, five compounds, including compound 5, demonstrated effective depigmentation activity in vivo in zebrafish embryos, and their depigmentation efficacy was similar to that of kojic acid, even at concentrations hundreds of times lower. These findings suggest that 6-(substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole compounds may be promising anti-melanogenic agents. Full article

Background: Skin aging is a complex biological process affected by internal and external factors that disrupt the skin structure, especially in sun-exposed areas. Elastin and collagen in the dermis layer, responsible for the skin’s resistance and elasticity, have been the main subject of research. Since tyrosinase (TYR) is an enzyme found in different organisms and plays an essential role in melanogenesis, inhibitors of this enzyme have been the target mechanism for skin-bleaching product research. Methods: We selected the plant species Cotinus coggygria Scop., Garcinia mangostana L., Pistacia vera L., Vitis vinifera L., and propolis, which exhibited activity against a minimum of three target enzymes—elastase, collagenase, and TYR—in our previous screening study to find the suitable raw material for a cosmetic product. In the current research, the extracts from these samples were tested through a cell-free enzyme assay using validated elastase, collagenase, and TYR inhibition kits. We also performed the safety and efficacy tests of the selected extracts with 2D/3D cell culture methods. Results: Our data revealed the propolis extract among the tested ones displayed remarkable anti-inflammatory activity in the 2D (NF-κB induction: 10.81%) and 3D assays. Cotinus coggygria leaf and Garcinia mangostana shell extracts exhibited anti-inflammatory activity in the 2D luciferase reporter assay via TNFα addition. C. coggygria leaf, V. vinifera (grape) seed, and propolis extracts were selected for testing in 3D cell culture methods based on the 2D cytotoxicity results with cell viability values of 54.75%, 93.19%, and 98.64% at 34.25 µg/mL, respectively. The general phytochemical profiles of these three extracts were examined in terms of 53 phenolic compounds with LC-MS/MS, revealing that quinic acid, epicatechin, and acacetin were the dominant phenolics among the tested ones. Conclusions: It is the first study conducted to evaluate the use of the extracts indicated above in cosmetics by employing procedures involving 3D cell culture. Full article

Background/Objectives: This study was used in silico modelling to search for potential tyrosinase protein inhibitors from a database of different core structures for IC₅₀ prediction. Methods: Four machine learning algorithms and topographical descriptors were tested for model construction. Results: A model based on multiple linear regression was the most robust, with only six descriptors, and validated by the Tropsha test with statistical parameters R² = 0.8687, Q²_LOO = 0.8030, and Q²_ext = 0.9151. From the screening of FDA-approved drugs and natural products, the pIC₅₀ values for 15,424 structures were calculated. The applicability domain analysis covered 100% of the external dataset and 71.22% and 73.26% of the two screening datasets. Fifteen candidates with pIC₅₀ above 7.6 were identified, with five structures proposed as potential tyrosinase enzyme inhibitors, which underwent ADME analysis. Conclusions: The molecular docking analysis was performed for the dataset used in the training-test process and for the fifteen structures from the screening dataset with potential pharmaceutical tyrosinase inhibition, followed by molecular dynamics studies for the top five candidates with the highest predicted pIC₅₀ values. The new use of these five candidates in tyrosinase inhibition is highlighted based on their promising application in melanoma treatment. Full article