Tyrosinase Inhibitory Activity Research Articles

Investigating the potential mechanisms of Litsea cubeba essential oil for anti-melanoma through experimental validation, network pharmacology, and molecular docking analysis

Abstract Objectives Melanoma remains a challenge due to the lack of effective and low-toxicity treatments. Litsea cubeba essential oil (LEO), known for its tyrosinase inhibitory activity, has shown promise as an anti-melanoma compound, although robust scientific evidence is lacking. Methods We conducted GC-MS analysis to identify the major components of LEO and screened for effective components were further evaluated on A375 and HaCaT cells using the CCK-8 assay. Network pharmacology was employed to predict potential targets using PharmMapper and SwissTarget Prediction databases, with melanoma-related targets sourced from the GeneCards database. Protein–protein interaction (PPI) network was created using STRING and Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed through the DAVI database. Additionally, we constructed a natural product-main components-core targets-pathways-disease (NMCPD) network in Cytoscape and conducted molecular docking using PyMOL and Autodock Vina. Results GC-MS analysis revealed neral (cis-citral) and geranial (trans-citral) as the primary active components of LEO. Cell assays demonstrated that a citral mixture, in combination with LEO, effectively inhibited A375 cell growth with IC50 values of 35.94 ± 1.23 μM and 12.00 ± 0.96 μg/mL, while exhibiting minimal toxicity to HaCaT cells with IC50 values of 67.72 ± 2.96 μM and 22.32 ± 2.53 μg/mL. Screening identified10 hub targets among 190 common targets between drug and disease-related targets. KEGG pathway enrichment analysis suggested therapeutic effects of citral on melanoma by modulating signaling pathways. Molecular docking revealed strong binding affinity of neral and geranial with RXRA and ESR1, suggesting that citral, the principal LEO component, regulates multiple pathways for potential melanoma therapy. Conclusions These findings support the potential utility of LEO as a treatment for melanoma and highlight the importance of exploring tyrosinase inhibitors for the development of novel anti-melanoma drugs.

Ultrasonic-Assisted Biphasic Aqueous Extraction of Polyphenols from Vaccinium Dunalianum Leaves: Optimization, Antioxidant, and Tyrosinase Inhibition Activities.

To optimize the ultrasonic-assisted biphasic aqueous extraction conditions for polyphenolic compounds from Vaccinium dunalianum Wight leaves and investigate their antioxidant and tyrosinase inhibition activities, single-factor experiments were conducted to investigate the effects of ethanol volume fraction (%), ammonium sulfate mass fraction (%), solid-liquid ratio (g/mL), ultrasonic temperature (°C), and ultrasonic time (min) on polyphenolic content during extraction. Based on these experiments, three key factors influencing extraction were selected for response surface methodology (RSM) optimization. The results indicated that under conditions of 26% ethanol, 20% ammonium sulfate, a solid-liquid ratio of 1:30, and extraction for 35 minutes at 50°C, the polyphenol content reached 61.62 mg/g. The relative contents of 6'-O-caffeoylarbutin, β-arbutin, and chlorogenic acid were 34.45%, 4.56%, and 31.06%, respectively. The DPPH· and ABTS+· scavenging rates were above 95% and 96%, respectively, and the ferric reducing ability exhibited a significant dose-effect relationship. The inhibition rates of monophenolase and diphenolase activities of tyrosinase were 43.84% and 35.73%, respectively. The optimized process for ultrasonic-assisted biphasic aqueous extraction of polyphenols from Vaccinium dunalianum Wight leaves demonstrated significant antioxidant and tyrosinase inhibition activities.

Comparative study on metabolite variations of two rose teas by plant metabolomics and revealing their skin-whitening candidates by spectrum-effect relationship analysis.

Rosa rugosa var. plena Rehd (CBR) and Rosa chinensis cv. "JinBian" (JBR) are two common species used in rose tea among different original species. CBR, the officially documented original plant of the rose species for food and medicinal purposes, is more costly than JBR. With increasing demand for different rose teas, it is meaningful to compare the chemical constituents for their quality control and reveal their skin-whitening components that will provide in-depth insights for the expansion of the rose tea industry. This study aims to reveal the chemical variances between CBR and JBR and determine their skin-whitening components. A strategy obtained by combining MS-based plant-metabolomics with spectrum-effect relationship analysis has been proposed for unveiling chemical differences between CBR and JBR and further exploring their potential skin-whitening components. A total of 2030 metabolites were found that revealed considerable differences between CBR and JBR. The results of bioactivity assay demonstrated that JBR exhibited stronger tyrosinase inhibition activity than CBR. Six potential skin-whitening compounds (di-O-galloyl-HHDP-glucoside, tri-O-galloyl-HHDP-glucoside, spiraeoside, quinic acid, rugosin A, and 1,2,3,6-tetra-O-galloyl-glucose) were discovered as potential tyrosinase inhibitors, via spectrum-effect relationship analysis. This is the first time that di-O-galloyl-HHDP-glucoside, tri-O-galloyl-HHDP-glucoside, rugosin A, and 1,2,3,6-tetra-O-galloyl-glucose have been reported with tyrosinase inhibitory activity. Additionally, molecular docking analysis was used to reveal the inhibition mechanism of these compounds toward tyrosinase. The finding of this study will be of great importance for the quality control of the two types of rose teas, and the revealed active ingredients will provide in-depth insights for the expansion of the rose tea industry.

Inhibitive Mechanism of Loquat Flower Isolate on Tyrosinase Activity and Melanin Synthesis in Mouse Melanoma B16 Cells

Melanin naturally exists in organisms and is synthetized by tyrosinase (TYR); however, its over-production may lead to aberrant pigmentation and skin conditions. Loquat (Eriobotrya japonica (Thunb.) Lindl.) flowers contain a variety of bioactive compounds, while studies on their suppressive capabilities against melanin synthesis are limited. Loquat flower isolate product (LFP) was obtained by ethanol extraction and resin purification, and its inhibitory efficiency against TYR activity was investigated by enzyme kinetics and multiple spectroscopy analyses. In addition, the impact of LFP on melanin synthesis-related proteins’ expression in mouse melanoma B16 cells was analyzed using Western blotting. HPLC-MS/MS analysis indicated that LFP was composed of 137 compounds, of which 12 compounds, including flavonoids (quercetin, isorhamnoin, p-coumaric acid, etc.) and cinnamic acid and its derivatives, as well as benzene and its derivatives, might have TYR inhibitory activities. LFP inhibited TYR activity in a concentration-dependent manner with its IC50 value being 2.8 mg/mL. The inhibition was an anti-competitive one through altering the enzyme’s conformation rather than chelating copper ions at the active center. LFP reduced the expression of TYR, tyrosinase-related protein (TRP) 1, and TRP2 in melanoma B16 cells, hence inhibiting the synthesis of melanin. The research suggested that LFP had the potential to reduce the risks of hyperpigmentation caused by tyrosinase and provided a foundation for the utilization of loquat flower as a natural resource in the development of beauty and aging-related functional products.

Exploring the bioactive potential of Mentha longifolia from Northeast India: an inclusive study on phytochemical composition and biological activities

Mentha longifolia (Lamiaceae) is regarded as highly valuable aromatic medicinal species with wide range of pharmaceutical application. In the present work, leaf essential oil of M. longifolia was applied for the assessment of in vitro pharmacological potentials and compositional analysis. A sum of 15 compounds were detected by GC-FID and GC-MS analysis of M. longifolia essential oil with total area of 99.98% where major compounds were carvone (59.56%), D-limonene (20.81%), eucalyptol (10.08%). The anti-oxidant potency of M. longifolia was estimated using two methods viz., ABTS (2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid) and DPPH (2,2-diphenyl-1-picrylhydrazyl) assay where M. longifolia essential oil showed moderate anti-oxidant potency. M. longifolia essential oil revealed high anti-inflammatory and tyrosinase inhibitory activity with an IC50 value 3.68 μL/mL and 1.22 μL/mL respectively compared to standard sodium diclofenac (5.33 μL/mL) and kojic acid (2.28 μL/mL). The acetylcholinesterase (AchE) inhibitory and genotoxic assay was performed, where M. longifolia essential oil revealed strong anti-acetylcholinesterase and anti-genotoxic activity. Anti-microbial potential of M. longifolia essential oil was also where strong anti-bacterial activity was shown against Salmonella typhimurium, Bacillus cereus, Staphylococcus aureus, Micrococcus luteus. For anti-fungal activity, M. longifolia essential oil showed no zone of inhibition against any used strains except Aspergillus flavus. From the present research it was established that M. longifolia essential oil possesses pharmaceutical potential with strong AchE inhibitory, anti-inflammatory, anti-microbial, anti-tyrosinase, anti-genotoxic and anti-oxidant activity which can be used for plant-based drug development in future endeavor.

Study of the Effects of Novel Analogs of Calebin-A on Melanogenesis

In our previous study, we documented the anti-melanogenic efficacy of calebin-A (CBA), which is a curcuminoid analog. The effects of its newly synthesized analogs, i.e., bisdemethoxy calebin (BD), demethoxycalebin-1 (DA1), demethoxycalebin-2 (DA2), and tetrahydrocalebin-A (THCBA), on melanogenesis have not been examined yet. Herein, we evaluated these four CBA analogs to determine their impacts on the enzymatic activity of mushroom tyrosinase. Additionally, we examined their effects on melanogenesis and the tyrosinase activity in B16F10 mouse and MNT-1 human melanoma cells. The antioxidant activity of the analogs was also assessed. Our results revealed that BD was ineffective, while DA1 and DA2 showed similar antioxidant activities, with THCBA exhibiting the greatest antioxidant activity. Next, the diphenolase activity assay results revealed that DA1 showed the most excellent inhibitory efficacy, DA2 and BD showed similar inhibition profiles, and THCBA was ineffective. In addition, the results of the monophenolase activity showed a similar pattern, except that THCBA suppressed the activity. The four analogs were evaluated for any cytotoxicity over a 48 h duration in B16F10 and HaCaT keratinocytes, where DA1 exerted cytotoxicity at the concentration of 50 µM. Based on this, the analogs were evaluated over a 10–50 µM concentration range, while DA1 was evaluated over 10–35 µM. BD showed the greatest efficacy at multiple concentrations in significantly diminishing melanogenesis in hormone-stimulated B16F10 cells, while DA1 and DA2 suppressed melanin at 35 and 50 µM, respectively, and THCBA stimulated melanogenesis at 50 µM. In addition, BD and DA1 suppressed tyrosinase activity in B16F10 cells, with no effect in the case of DA2 and THCBA analogs. However, in MNT-1 cells, only DA1 showed efficacy in suppressing melanin production while the other three analogs were ineffective. Interestingly, BD and DA1 suppressed MNT-1 cell tyrosinase activity. Collectively, our results indicate that of the four analogs, DA1 merits further investigation as a potential compound for hyperpigmentation skin disorders. Additional research is necessary to delineate the molecular mechanisms underlying the melanogenesis-inhibitory effect of CBA analogs and examine their efficacy in diminishing melanogenesis in normal human melanocytes.

Elucidating bis-pyrimidines as new and efficient mushroom tyrosinase inhibitors: synthesis, SAR, kinetics and computational studies.

In this study, a series of novel bis-pyrimidine derivatives (1P-8P) were designed, synthesized, characterized, and investigated for their in vitro inhibitory activity against mushroom tyrosinase, an enzyme critical in melanin biosynthesis and implicated in various hyperpigmentation disorders. To the best of our knowledge, the bispyrimidine scaffold has been evaluated for the first time for its tyrosinase inhibitory activity. Their inhibitory activities were assessed, revealing inhibition with IC50 values in the micromolar range. Additionally, this series of compounds were found to inhibit tyrosinase activity in a mixed-type manner, with IC50 values ranging from 12.36 ± 1.24 to 86.67 ± 3.08 μM. To further elucidate the binding interactions, molecular docking simulations were performed, identifying key residues in the active site responsible for binding affinity. Furthermore, molecular dynamics (MD) simulations were conducted to assess the dynamic behavior, stability, and binding affinity of the most potent inhibitor, compound 6P. Quantitative Structure-Activity Relationship (QSAR) models were developed to correlate the structural features of the bis-pyrimidines with their inhibitory activity, providing insights into the structure-activity relationships (SAR) that govern their potency. The experimental and theoretical findings demonstrated excellent agreement. These findings pave the way for the development of novel bis-pyrimidine-based therapeutic agents for treating hyperpigmentation and related conditions.

Cyclo(l-Pro-l-Tyr) Isolated from the Human Skin Commensal Corynebacterium tuberculostearicum Inhibits Tyrosinase.

Melanin is produced by melanocytes to protect human skin from harmful ultraviolet radiation. During skin cell renewal, melanin and dead skin cells are disposed of. However, prolonged exposure to ultraviolet rays or aging can disturb this cycle, leading to skin hyperpigmentation due to melanin accumulation. Tyrosinase is a crucial enzyme involved in melanin biosynthesis. Although various compounds, including tyrosine inhibitors, that counteract melanin accumulation have been reported, some, such as hydroquinone, are toxic and can cause vitiligo. Meanwhile, the skin is the largest organ and the outermost layer of the immune system, containing a diverse range of bacteria that produce low-toxicity compounds. In the current study, we aim to identify metabolites produced by skin microbiota that inhibit tyrosinase. Specifically, mushroom tyrosinase served as the study model. Following commensal skin bacteria screening, Corynebacterium tuberculostearicum was found to inhibit tyrosinase activity. The active compound was cyclo(l-Pro-l-Tyr); commercially available cyclo(l-Pro-l-Tyr) also exhibited inhibitory activity. Docking simulations suggested that cyclo(l-Pro-l-Tyr) binds to the substrate-binding site of mushroom tyrosinase, obstructing the substrate pocket and preventing its activity. Hence, cyclo(l-Pro-l-Tyr) might have potential applications as a cosmetic agent and food additive.

Cyclo(l-Pro-l-Tyr) Isolated from the Human Skin Commensal Corynebacterium tuberculostearicum Inhibits Tyrosinase

Melanin is produced by melanocytes to protect human skin from harmful ultraviolet radiation. During skin cell renewal, melanin and dead skin cells are disposed of. However, prolonged exposure to ultraviolet rays or aging can disturb this cycle, leading to skin hyperpigmentation due to melanin accumulation. Tyrosinase is a crucial enzyme involved in melanin biosynthesis. Although various compounds, including tyrosine inhibitors, that counteract melanin accumulation have been reported, some, such as hydroquinone, are toxic and can cause vitiligo. Meanwhile, the skin is the largest organ and the outermost layer of the immune system, containing a diverse range of bacteria that produce low-toxicity compounds. In the current study, we aim to identify metabolites produced by skin microbiota that inhibit tyrosinase. Specifically, mushroom tyrosinase served as the study model. Following commensal skin bacteria screening, Corynebacterium tuberculostearicum was found to inhibit tyrosinase activity. The active compound was cyclo(l-Pro-l-Tyr); commercially available cyclo(l-Pro-l-Tyr) also exhibited inhibitory activity. Docking simulations suggested that cyclo(l-Pro-l-Tyr) binds to the substrate-binding site of mushroom tyrosinase, obstructing the substrate pocket and preventing its activity. Hence, cyclo(l-Pro-l-Tyr) might have potential applications as a cosmetic agent and food additive.

Phytochemistry, Anti-Tyrosinase, and Anti-Diabetes Studies of Extracts and Chemical Constituents of Dicerothamnus rhinocerotis Leaves

Dicerothamnus rhinocerotis (L.f.) Koekemoer, also known as rhinoceros bush and previously called Elytropappus rhinocerotis (L.f.) Less., is from the Asteraceae plant family. The plant is traditionally used to treat indigestion, stomach ulcers, influenza, and diarrhea. This study was aimed at investigating the phytochemistry, anti-glucosidase, anti-amylase, and anti-tyrosinase effects of D. rhinocerotis as research in this area is limited. The air-dried plant materials were macerated in 80% methanol (MeOH) and fractionated between hexane, dichloromethane (DCM), ethyl acetate (EtOAc), and butanol (BuOH). Column chromatography on silica gel was employed for the isolation of the compounds. A total of six compounds (1–6) were isolated from the fractions viz. acacetin (1), 15-hydroxy-cis-clerodan-3-ene-18-oic-acid (2), acacetin-7-glucoside (3), pinitol (4), apigenin (5), and β-sitosterol-3-O-glycoside (6). Compounds 2–4 and 6 are reported for the first time from this plant. Among the different fractions, the BuOH and EtOAc fractions had strong tyrosinase inhibitory activities with IC50 values of 13.7 ± 1.71 and 11.6 ± 2.68 µg/mL, respectively, while among the isolated compounds, apigenin (5) had the strongest inhibitory activity, with an IC50 of 14.58 µM, which competes favorably with Kojic acid (17.26 µM). The anti-glucosidase assay showed good activity in three of the fractions and compound 5, while the anti-amylase assays did not show significant inhibition activity.

Design, synthesis, and anti-melanogenic efficacy of 2-mercaptobenzoxazoles with nanomolar tyrosinase activity inhibition

Tyrosinase is a metalloenzyme that contains copper(II) ions. We designed and synthesized eight known low-molecular-weight 2-mercaptobenzoxazole (2-MBO) analogs as tyrosinase inhibitors. Our focus was on the mercapto functional group, which interacts with copper ions. Analogs 1–3 exhibited mushroom tyrosinase inhibitory activity at the nanomolar level and demonstrated strong potency with extremely low half-maximal inhibitory concentration (IC50) values of 80–90 nM for l-dopa and 100–240 nM for l-tyrosine. Analogs 2, 4, and 5 showed the most potent anti-melanogenic effects in B16F10 cells, and their mode of action was demonstrated by kinetic analysis. Their anti-melanogenic effects were similar to the tyrosinase inhibition results, suggesting that their anti-melanogenic effects could be attributed to their tyrosinase inhibitory ability. Experiments using copper-chelating activity assays and changes in tyrosinase inhibitory activity with and without CuSO4 demonstrated that 2-MBO analogs inhibit tyrosinase activity by chelating the copper ions of tyrosinase. In conclusion, the 2-MBO analogs show potential as anti-melanogenic agents with potent tyrosinase inhibitory activity.

Mechanism of the wine pomace tannin in hyperpigmentation inhibition: Impact on signaling pathways, cell proliferation, and tyrosinase activity

After winemaking, tannins with high polymerization remain in the pomace. Utilizing these tannin fractions is a concern for the wine industry. While tannins show potential in treating hyperpigmentation, their mechanisms in vivo and at the cellular level are unclear. Herein, pomace tannin fractions (PTFs) were isolated post-winemaking. Nuclear magnetic resonance spectroscopy and mass spectrometry analysis showed PTFs were composed of (epi)catechin gallate and (epi)catechin as terminal and extensional units, with polymerization degrees of 10, 16, and 35. In vivo studies demonstrated that PTFs removed ~76 % of skin melanin, comparable to hydroquinone. The inhibition by PTFs is due to: (1) Inhibition of the Wnt and melanogenesis pathways, downregulating key melanin synthesis proteins (TYR, TYRP1, TYRP2); (2) Inducing cell cycle arrest at the G1/S checkpoint, disrupting DNA, decreasing mitochondrial membrane potential and integrity, and slowing melanocyte proliferation; (3) Superior tyrosinase inhibitory activity by binding to tyrosinase, chelating copper ions, and demonstrating antioxidant properties. These findings suggest that PTFs inhibit melanin synthesis by the combination of the above mentioned ways, supporting the medical use of winemaking tannins.

Synthesis, Characterization, Enzyme Inhibition and Molecular Docking Studies of Benzothiazole Derivatives Bearing Alkyl Phenyl Ether Fragments

Novel benzothiazole derivatives containing alkyl/benzyl phenyl ether fragments have been synthesized through two step reaction process. Initially, 2-hydroxybenzaldehyde was refluxed with 2-aminothiophenol in the presence of sodium metabisulfite (Na2S2O5) in DMF solvent followed by treating it with alkyl and aromatic halides in the presence of triethylamine in dry acetone to get the product derivatives (1-11) in better yields. These products were characterized by means of modern spectroscopic (1H, 13C-NMR and HR-ESI-MS) techniques and screened for in vitro tyrosinase inhibitory activity. In the series, three compounds 13 (IC50 = 8.6 ± 0.2 µM), 3 (IC50 = 11.1 ± 0.5 µM), and 12 (IC50 = 18.2 ± 0.1 µM) showed excellent inhibition comparing with the standard kojic acid (IC50 = 17.8 ± 0.6 µM). Likewise, six compounds 9, 10, 11, 2, 4, and 5 attributed significant activity ranging from IC50 22.6 ± 0.8 to 29.2 ± 0.3 µM. Besides, compound 6 (IC50 = 40.6 ± 0.5 µM) was found least active while two compounds 7 and 8 were found inactive. The molecular docking study on molecules and their interaction with tyrosinase protein revealed a consistent pattern in the activity of kojic acid. The electronic characteristics of active derivatives 2, 3, 9-12, and kojic acid were examined using the TD-DFT approach. The study found that the HOMO and LUMO were concentrated on the π-conjugated system of the benzothiazole rings moiety, indicating a significant delocalization of electrons. The study also found that compounds compared to kojic acid, possess chemical hardness and stability properties, with lower electrophilicity index indicating higher bioactivity and lower toxicity. The study also highlighted the importance of comprehensive ADMET profiling in early drug development to ensure safety and efficacy.

Effects of Vitamin C and SH-Polypeptide-10 Cosmetic Ingredients on Wrinkle Improvement and Skin Whitening

In this study, 20 female subjects in their 30s to 50s used cosmetics containing the main ingredients vitamin C and SH-Polypeptide-10 in an environment exposed to ultraviolet rays, and underwent clinical trials to determine the effects of improving wrinkles, brightness, and whitening of the skin. Efficacy evaluation was performed. Wrinkles around the eyes significantly decreased from 0.0592 to 0.0507(p<0.001), and the wrinkle improvement effect decreased by 16.78%(p<0.05). Skin brightness significantly decreased from 65.44 to 67.04 in the experimental group(p<0.001), and skin brightness increased by 2.45%(p<0.05). Additionally, the skin whitening effect significantly decreased from 66.38 to 55.51(p<0.001), and melanin pigment decreased by 19.57%(p<0.05). The cosmetics used in this experiment were shown to have antioxidant effects that protect cells from oxidative stress, increase transdermal permeability, promote epidermal cell growth and cell regeneration, inhibit tyrosinase activity and promote collagen formation. Overall, the use of cosmetics containing vitamin C and SH-Polypeptide-10 as main ingredients resulted in significant improvement in the experimental group, which can be seen as having a positive effect on improving wrinkles around the eyes and skin whitening.

Efficiency of freeze- and spray-dried microbial preparation as active dried starter culture in kombucha fermentation.

Kombucha is a widely consumed fermented beverage produced by fermenting sweet tea with a symbiotic culture of bacteria and yeast (SCOBY). The dynamic nature of microbial communities in SCOBY may pose challenges to production scale-up due to unpredictable variations in microbial composition. Using identified starter strains is a novel strategy to control microorganism composition, thereby ensuring uniform fermentation quality across diverse batches. However, challenges persist in the cultivation and maintenance of these microbial strains. This study examined the potential of microencapsulated kombucha fermentation starter cultures, specifically Komagataeibacter saccharivorans, Levilactobacillus brevis and Saccharomyces cerevisiae, through spray-drying and freeze-drying. Maltodextrin and gum arabic-maltodextrin were employed as carrier agents. Our results revealed that both spray-dried and freeze-dried samples adhered to physicochemical criteria, with low moisture content (2.18-7.75%) and relatively high solubility (65.75-87.03%) which are appropriate for food application. Freeze-drying demonstrated greater effectiveness in preserving bacterial strain viability (88.30-90.21%) compared to spray drying (74.92-78.66%). Additionally, the freeze-dried starter strains demonstrated similar efficacy in facilitating kombucha fermentation, compared to the SCOBY group. The observations included pH reduction, acetic acid production, α-amylase inhibition and elevated total polyphenol and flavonoid content. Moreover, the biological activity, including antioxidant potential and in vitro tyrosinase inhibition activity, was enhanced in the same pattern. The freeze-dried strains exhibited consistent kombucha fermentation capabilities over a three-month preservation, regardless of storage temperature at 30 or 4 °C. These findings highlight the suitability of freeze-dried starter cultures for kombucha production, enable microbial composition control, mitigate contamination risks and ensure consistent product quality. © 2024 Society of Chemical Industry.

Anti-Melanogenic Activity of Ethanolic Extract from Garcinia atroviridis Fruits Using In Vitro Experiments, Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Melanin, the pigment responsible for human skin color, increases susceptibility to UV radiation, leading to excessive melanin production and hyperpigmentation disorders. This study investigated the ethanolic extract of Garcinia atroviridis fruits for its phenolic and flavonoid contents, antioxidant activity, and impact on melanogenesis pathways using qRT-PCR and Western blot analysis. Utilizing network pharmacology, molecular docking, and dynamics simulations, researchers explored G. atroviridis fruit extract's active compounds, targets, and pharmacological effects on hyperpigmentation. G. atroviridis fruit extract exhibited antioxidant properties, scavenging DPPH• and ABTS•+ radicals radicals and chelating copper. It inhibited cellular tyrosinase activity and melanin content in stimulated B16F10 cells, downregulating TYR, TRP-1, phosphorylated CREB, CREB, and MITF proteins along with transcription levels of MITF, TYR, and TRP-2. LC-MS analysis identified thirty-three metabolites, with seventeen compounds selected for further investigation. Network pharmacology revealed 41 hyperpigmentation-associated genes and identified significant GO terms and KEGG pathways, including cancer-related pathways. Kaempferol-3-O-α-L-rhamnoside exhibited high binding affinity against MAPK3/ERK1, potentially regulating melanogenesis by inhibiting tyrosinase activity. Stable ligand-protein interactions in molecular dynamics simulations supported these findings. Overall, this study suggests that the ethanolic extract of G. atroviridis fruits possesses significant antioxidant, tyrosinase inhibitory, and anti-melanogenic properties mediated through key molecular targets and pathways.

Comparative evaluation of six commercial adult toothpaste formulations reveals cytotoxicity and altered functions in a human oral melanocyte model: an in vitro study.

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 24h. 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 24h. 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.

Phytochemical study, antioxidant and tyrosinase inhibitory activities of Pentzia monodiana Maire

Chemical investigation of the aerial parts of Pentzia monodiana Maire led to the isolation and identification of one sesquiterpene lactone glucoside of the guaianolide type (dihydropseudoivalin-4-O-β-d-glucopyranoside), along with nine known compounds including one diterpenoid, two sesquiterpenoids, three lignanes and three flavonoids. Their structures were established on the basis of spectroscopic analysis. All these compounds were evaluated for their DPPH radical scavenging and tyrosinase inhibitory activities. Only lignanes and flavonoids showed good to moderate DPPH radical scavenging activity with EC50 ranging from 10.6 to 47.5 μM. The new sesquiterpene lactone glucoside showed low tyrosinase inhibitory activity whereas the isolated lignanes and flavonoids exhibited a moderate activity with IC50 ranging from 45.4 to 97.2 μM).

Phytochemical profiling, antioxidant, and tyrosinase inhibitory potential of the Acacia cyclops trunk bark: in vitro combined with in silico approach.

The aim of this study was to analyze the phytochemical profile of Acacia cyclops trunk bark ethyl acetate extract using LC-tandem mass spectrometry for the first time, along with evaluating its antioxidant and anti-tyrosinase properties. Consequently, we determined the total phenolic and flavonoid contents of the extract under investigation and identified and quantified 19 compounds, including phenolic acids and flavonoids. In addition to assessing their antioxidant potential against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis-[3-ethylbenzothiazoline-6-sulfonic] acid) assays, in vitro and in silico studies were conducted to evaluate the tyrosinase inhibitory properties of the A. cyclops extract. The ethyl acetate trunk bark extract exhibited a substantial total phenolic content and demonstrated significant antioxidant activity in terms of free radical scavenging, as well as notable tyrosinase inhibitory action (half-maximal inhibitory concentration [IC50] = 14.08 ± 1.10 μg/mL). The substantial anti-tyrosinase activity of the examined extract was revealed through molecular docking analysis and druglikeness prediction of the main selected compounds. The findings suggest that A. cyclops extract holds promise as a potential treatment for skin hyperpigmentation disorders.

Unveiling the Potential of Ultrasonic-Assisted Ethanol Extract from Sargassum horneri in Inhibiting Tyrosinase Activity and Melanin Production in B16F10 Murine Melanocytes.

Melanogenesis, regulated by genetic, hormonal, and environmental factors, occurs in melanocytes in the basal layer of the epidermis. Dysregulation of this process can lead to various skin disorders, such as hyperpigmentation and hypopigmentation. Therefore, the present study investigated the effect of ultrasonic-assisted ethanol extract (SHUE) from Sargassum horneri (S. horneri), brown seaweed against melanogenesis in α-melanocyte-stimulating hormone (MSH)-stimulated B16F10 murine melanocytes. Firstly, yield and proximate compositional analysis of the samples were conducted. The effect of SHUE on cell viability has been evaluated by using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After that, the melanin content and cellular tyrosinase activity in α-MSH-stimulated B16F10 murine melanocytes were examined. Western blot analysis was carried out to investigate the protein expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2). In addition, the effect of extracellular signal-regulated kinase (ERK) on the melanogenesis process was assessed via Western blotting. As per the analysis, SHUE contained the highest average yield on a dry basis at 28.70 ± 3.21%. The findings showed that SHUE reduced the melanin content and cellular tyrosinase activity in α-MSH-stimulated B16F10 murine melanocytes. Additionally, the expression levels of MITF, TRP1, and TRP2 protein were significantly downregulated by SHUE treatment in α-MSH-stimulated B16F10 murine melanocytes. Moreover, SHUE upregulated the phosphorylation of ERK and AKT in α-MSH-stimulated B16F10 murine melanocytes. In addition, experiments conducted using the ERK inhibitor (PD98059) revealed that the activity of SHUE depends on the ERK signaling cascade. These results suggest that SHUE has an anti-melanogenic effect and can be used as a material in the formulation of cosmetics related to whitening and lightening.