This study aims to compare six commercial adult toothpaste (labeled as A, B, C, D, E, and F) for cytotoxicity and melanocyte function alterations in vitro using primary human epidermal melanocytes from a Caucasian donor (HEMn-LP cells) as a model of oral melanocytes. Cells were incubated with toothpaste extracts (50% w/v) in culture media at dilutions (1:25, 1:50, 1:100, 1:200, 1:500, 1:800, and 1:1000) for 24 h. MTS and LDH assays were used to assess cytotoxicity. The effects of noncytotoxic toothpaste concentrations on melanocyte functional endpoints were then examined using spectrophotometric methods. All toothpaste showed concentration-dependent cytotoxicity that was heterogeneous across toothpaste containing SLS detergent. IC50 values of cytotoxicity followed the order: A = E > C > B > D > F. To compare toothpaste, they were tested at 1:800 and 1:1000 dilutions that were noncytotoxic after 24 h. None of the toothpaste affected cellular melanin production. However, toothpaste A, C, and D suppressed tyrosinase activity at both dilutions, while toothpaste B suppressed tyrosinase activity only at 1:800 dilution. Toothpaste A, C, E, and F elevated ROS production at 1:800 dilution, with no change at 1:1000 dilution. Toothpaste has a heterogeneous effect on melanocytes. Toothpaste B, E, and F at 1:1000 dilution were the safest as they did not alter melanocyte functions at this dilution, although toothpaste F is the least cytotoxic of these. Future studies are necessary to expand these results in a physiological environment of oral tissue. The findings of this study provide novel insight into the biocompatibility studies of toothpaste on oral melanocytes. They can aid dental practitioners and consumers in selecting noncytotoxic toothpaste that do not contribute to ROS generation by melanocytes in the oral cavity or lead to cytotoxicity and impaired cellular function.

Guava (Psidium guajava) is a plant widely distributed in tropical and subtropical regions. Its leaves contain a large amount of physiological molecules such as flavonoid, sesquiterpene, triterpenoid, coumarin, alkaloid, and tannin molecules with antioxidative and anti-inflammatory effects. In this study, the use of concentrated P. guajava leaf extract molecules as a functional natural material was evaluated by confirming the extract\'s antioxidative, antibacterial, tyrosinase activity inhibition, and collagenase activity inhibition effects and its trans-2-nonenal removal ability. As a result of the analysis of the antioxidant and antibacterial components of concentrated P. guajava leaf extract molecules through GC-MS, a large amount of aromatic hydrocarbon molecules were detected. When different concentrations of ethanol were used for extraction, the leaf extract concentrated with 70% ethanol showed the most effective active molecules. As a result of measuring DPPH radical scavenging activity, a concentration-dependent antioxidant activity was confirmed. The antioxidant activity tended to increase when the ethanol content used for extraction was increased. Molecules such as 2,4-di-tert-butylphenol, caryophyllene oxide, and γ-muurolene in P. guajava leaf extract concentrate appeared to have antibacterial activities against S. aureus bacteria known to cause atopy. As ethanol content increased, the inhibitory effect on tyrosinase activity was increased. In addition, when ethanol content was 50%, the concentrated leaf extract was able to remove trans-2-nonenal by 52.4%. As a result of determining the concentrated leaf extract\'s collagenase inhibition activity, an inhibition rate close to that of ascorbic acid, a positive control, was confirmed. The concentrated guajava leaf extract molecules were confirmed to have whitening and wrinkle-improving functionality. Thus, the P. guajava leaf extract has high potential as a food and natural cosmetic material.

Cyanidin, peonidin and cyanidin-3-galactoside are the common anthocyanins with a variety of biological activities. Tyrosinase is a speed-limiting enzyme associated with melanin production. The inhibition of tyrosinase activity can prevent melanin disease while contributing to whitening. The interaction behaviors of the three anthocyanins against tyrosinase have been discussed in this paper. Cyanidin has strongest inhibitory effect on tyrosinase, and then peonidin, cyanidin-3-galactoside. Furthermore, the inhibition of tyrosinase by the three anthocyanins is mixed modes. The three anthocyanins can induce the static fluorescence quenching of tyrosinase. Cyanidin exhibits strongest binding affinity on tyrosinase, and then peonidin, cyanidin-3-galactoside based on Ka values obtain by fluorescence analysis. The binding of all anthocyanin to tyrosinase induce its conformation changes. According to molecular docking and fluorescence studies, they bind to tyrosinase by hydrogen bond and van der Waals force. In addition, the optimal modes of the three anthocyanins with tyrosinase are predicated by molecular docking. This work emphasizes that cyanidin, peonidin and cyanidin-3-galactoside may be potential drugs for the treatment of diseases caused by melanin.

Currently, there is an increased interest from both scientists and consumers in the application of cannabis/hemp/phytocannabinoids in skin-related disorders. However, most previous investigations assessed the pharmacological properties of hemp extracts, cannabidiol (CBD), or tetrahydrocannabinol (THC), with very few studies focusing on minor phytocannabinoids from hemp. In this context, the current work explored the in vitro anti-melanoma, anti-melanogenic, and anti-tyrosinase effects of cannabidiol (CBD) and three minor phytocannabinoids, namely cannabigerol (CBG), cannabinol (CBN), and cannabichromene (CBC). Among the tested human malignant melanoma cells (A375, SH4, and G361), only A375 cells were highly susceptible to the 48 h treatment with the four phytocannabinoids (IC50 values between 12.02 and 25.13 μg/mL). When melanogenesis was induced in murine melanoma B16F10 cells by α-melanocyte stimulating hormone (αMSH), CBD, CBG, and CBN significantly decreased the extracellular (29.76-45.14% of αMSH+ cells) and intracellular (60.59-67.87% of αMSH+ cells) melanin content at 5 μg/mL. Lastly, CBN (50-200 μg/mL) inhibited both mushroom and murine tyrosinase, whereas CBG (50-200 μg/mL) and CBC (100-200 μg/mL) down-regulated only the mushroom tyrosinase activity; in contrast, CBD was practically inactive. The current data show that tyrosinase inhibition might not be responsible for reducing the melanin biosynthesis in α-MSH-treated B16F10 cells. By evaluating for the first time the preliminary anti-melanoma, anti-melanogenic, and anti-tyrosinase properties of CBN and CBC and confirming similar effects for CBD and CBG, this study can expand the utilization of CBD and, in particular, of minor phytocannabinoids to novel cosmeceutical products for skin care.

In the field of biocatalysis, the implementation of sustainable processes such as enzyme immobilization or employment of environmentally friendly solvents, like Deep Eutectic Solvents (DESs) are of paramount importance. In this work, tyrosinase was extracted from fresh mushrooms and used in a carrier-free immobilization towards the preparation of both non-magnetic and magnetic cross-linked enzyme aggregates (CLEAs). The prepared biocatalyst was characterized and the biocatalytic and structural traits of free tyrosinase and tyrosinase magnetic CLEAs (mCLEAs) were evaluated in numerous DES aqueous solutions. The results showed that the nature and the concentration of the DESs used as co-solvents significantly affected the catalytic activity and stability of tyrosinase, while the immobilization enhanced the activity of the enzyme in comparison with the non-immobilized enzyme up to 3.6-fold. The biocatalyst retained the 100% of its initial activity after storage at -20 °C for 1 year and the 90% of its activity after 5 repeated cycles. Tyrosinase mCLEAs were further applied in the homogeneous modification of chitosan with caffeic acid in the presence of DES. The biocatalyst demonstrated great ability in the functionalization of chitosan with caffeic acid in the presence of 10% v/v DES [Bet:Gly (1:3)], enhancing the antioxidant activity of the films.

The presence of phenobarbital and formaldehyde in drugs, food, and beverages can lead to various health issues, including inflammation, oncogenesis, and neurological distress. Psychological stress leads to mood fluctuations and the onset of skin inflammation. Skin inflammation has a range of causes, including chemicals, heavy metals, infection, immune-related disorders, genetics, and stress. The various treatments for skin inflammation include medical and cosmetic creams, diet changes, and herbal therapy. In this study, we investigated the effects of Avocom-M and pomegranate seed oil extract (PSOE) against phenobarbital- and formaldehyde-induced skin biochemical changes in rats. We analyzed the constituents of PSOE using gas chromatography-mass spectrometry and inductively coupled plasma-mass spectrometry. We also observed biochemical changes in the skin of human volunteers with and without TROSYD and PSOE as a skin cream. We compared the biochemical changes in human volunteers\' skin before treatment and 21 days after the treatment stopped. The outcomes showed an improvement in the rats\' biochemical status, due to PSOE and Avocom-M treatment. The human volunteers treated with TROSYD and PSOE showed substantial amelioration of skin inflammation. PSOE, Avocom-M, and TROSYD produced beneficial effects by reducing the levels of cyclooxygenase-2, lipid peroxidation, tyrosinase, hyaluronidase, elastase, collagenase, and nitric oxide in the animals tested on and in human volunteers.

UNASSIGNED: Melanin is the predominant pigment responsible for the color of skin, hair, iris of eyes, and oral mucosa. Tyrosinase (TYR) is the key enzyme involved in melanin synthesis. Studies in dermatology have shown a positive correlation between TYR enzyme levels and melanin pigmentation of the skin. However, no study has been conducted to assess TYR levels in the gingiva. Hence the present study was conducted to assess TYR levels in gingival melanin hyperpigmentation.
UNASSIGNED: To assess the TYR gene expression in gingiva in individuals with moderate to severe gingival melanin hyperpigmentation.
UNASSIGNED: Subjects with a chief complaint of blackish appearance of gums with an unesthetic smile were included in the study. Informed consent was obtained. Scaling and root planning were done and subjects were recalled after 2 weeks. The gingival depigmentation procedure was performed using the conventional scalpel technique under adequate local anesthesia. The selected sites underwent conventional gingival depigmentation technique using Bard-Parker handle no: 3 and blade no: 11. The excised layer of epithelium along with a thin layer of underlying connective was sent to the laboratory to assess the TYR gene expression by real-time polymerase chain reaction technique.
UNASSIGNED: The levels of the TYR enzyme activity in the gingival tissues from the selected sites were assessed. Table 1 and Graph 1 show the levels of TYR enzyme gene expression in the gingival tissue.
UNASSIGNED: TYR gene expression and the degree of gingival melanin hyperpigmentation are positively correlated. Hence the assessment of TYR enzyme activity in gingiva could be of great value in today\'s cosmetologically conscious individuals.

Psidium guajava (Guava tree) is one of the most widely known species in the family Myrtaceae. The Guava tree has been reported for its potential antioxidant, anti-inflammatory, antimicrobial, and cytotoxic activities. In the current study, the chemical compositions of the n-hexane extract and the essential oil of P. guajava were investigated using the GC/MS analysis, along with an evaluation of their antioxidant potential, and an investigation into the enzyme inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BchE), tyrosinase, α-amylase, and α-glucosidase. Moreover, molecular docking of the major identified active sites of the target enzymes were investigated. The chemical characterization of the n-hexane extract and essential oil revealed that squalene (9.76%), α-tocopherol (8.53%), and γ-sitosterol (3.90%) are the major compounds in the n-hexane extract. In contrast, the major constituents of the essential oil are D-limonene (36.68%) and viridiflorol (9.68%). The n-hexane extract showed more antioxidant potential in the cupric reducing antioxidant capacity (CUPRAC), the ferric reducing power (FRAP), and the metal chelating ability (MCA) assays, equivalent to 70.80 ± 1.46 mg TE/g, 26.01 ± 0.97 mg TE/g, and 24.83 ± 0.35 mg EDTAE/g, respectively. In the phosphomolybdenum (PM) assay, the essential oil showed more antioxidant activity equivalent to 2.58 ± 0.14 mmol TE/g. The essential oil demonstrated a potent BChE and tyrosinase inhibitory ability at 6.85 ± 0.03 mg GALAE/g and 61.70 ± 3.21 mg KAE/g, respectively. The α-amylase, and α-glucosidase inhibitory activity of the n-hexane extract and the essential oil varied from 0.52 to 1.49 mmol ACAE/g. Additionally, the molecular docking study revealed that the major compounds achieved acceptable binding scores upon docking with the tested enzymes. Consequently, the P. guajava n-hexane extract and oil can be used as a promising candidate for the development of novel treatment strategies for oxidative stress, neurodegeneration, and diabetes mellitus diseases.

UNASSIGNED: The high prevalence of skin hyperpigmentation makes it necessary to search for remedies that could hinder this process. Among such substances, tyrosinase inhibitors can be distinguished, which may be pyrimidine derivatives.
UNASSIGNED: This study aimed to investigate new compounds with anti-tyrosinase activity in 2-substituted tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one by an in vitro analysis and investigating their molecular docking.
UNASSIGNED: A molecular docking was performed using AutoDock 4.0 with the 3-dimensional structure of tyrosinase of the fungus Agaricus bisporus from the Protein Data Bank (PDB; rcsb.org) with identification number 2Y9X. A synthesis of 2-substituted tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one was carried out during the heterocyclization reaction of azomethine derivatives of 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide in glacial acetic acid with the addition of dimethyl sulfoxide. Tyrosinase activity was determined in vitro by the spectrophotometric method.
UNASSIGNED: Molecular docking data suggest the feasibility of synthesizing 2-substituted tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one as possible tyrosinase inhibitors. Of particular interest are compounds with hydroxy groups in the radical. Next, pharmacological screening showed that the leading compound is 4g. It is likely that metal-ligand interactions are the main interactions in the active site of tyrosinase because kojic acid, hydroquinone, and lactic acid (reference compounds), as well as compounds with only hydroxy groups in phenyl substituents (4b, 4c, and 4g), have the greatest anti-tyrosinase activity.
UNASSIGNED: As a result of molecular docking studies, the feasibility of synthesizing 2-substituted tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one as potential tyrosinase inhibitors was justified. 2-Substituted tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one was obtained using new synthesis conditions. The leading compound is 4g containing a fragment of 2,4-dihydroxybenzene.

Tyrosinase is a copper-containing key substance in the pigmentation of mammalian hair and skin. Melanin synthesis is influenced by a variety of extrinsic and internal variables, including hormone fluctuations, inflammation, ageing, and subsequent ultraviolet light exposure. Melasma, senile lentigines, freckles, and diminished colour are all undesirable side effects of excessive melanin production. The current review provides the pursuit of effective and safe tyrosinase inhibitors derived from medicinal plants and ascribes updated inferences on current practices. Commercially available tyrosinase inhibitors provide an even skin tone and are used clinically to treat hyperpigmentation and related disorders. This review focuses on the mechanism of melanogenesis and on experimentally verified potent and natural tyrosinase inhibitors. Bioactive compounds such as phenols, flavonoids, stilbenes, and few traditional herbal formulations from the Indian system of medicine, have been used for long in India and subcontinents for the effective management of melanogenesis and related problems. Scientific information was gathered from different sources of databases such as PubMed, Google Scholar, Springer, Scopus, and Science Direct, as well as the literature found in medicinal plant books. This critically summarized review ensures to aid researchers and enterprises working on tyrosinase inhibitors and on conditions associated with melanogenesis, to get one-step solutions for identifying more safe and effective natural remedies.