Tyrosinase Inhibition Research Articles

Exploration of Compounds with 2-Phenylbenzo[d]oxazole Scaffold as Potential Skin-Lightening Agents through Inhibition of Melanin Biosynthesis and Tyrosinase Activity.

Inspired by the potent tyrosinase inhibitory activity of phenolic compounds with a 2-phenylbenzo[d]thiazole scaffold, we explored phenolic compounds 1-15 with 2-phenylbenzo[d]oxazole, which is isosterically related to 2-phenylbenzo[d]thiazole, as novel tyrosinase inhibitors. Among these, compounds 3, 8, and 13, featuring a resorcinol structure, exhibited significantly stronger mushroom tyrosinase inhibition than kojic acid, with compound 3 showing a nanomolar IC50 value of 0.51 μM. These results suggest that resorcinol plays an important role in tyrosinase inhibition. Kinetic studies using Lineweaver-Burk plots demonstrated the inhibition mechanisms of compounds 3, 8, and 13, while docking simulation results indicated that the resorcinol structure contributed to tyrosinase binding through hydrophobic and hydrogen bonding interactions. Additionally, these compounds effectively inhibited tyrosinase activity and melanin production in B16F10 cells and inhibited B16F10 tyrosinase activity in situ in a concentration-dependent manner. As these compounds showed no cytotoxicity to epidermal cells, melanocytes, or keratinocytes, they are appropriate for skin applications. Compounds 8 and 13 demonstrated substantially higher depigmentation effects on zebrafish larvae than kojic acid, even at 800- and 400-times lower concentrations than kojic acid, respectively. These findings suggest that 2-phenylbenzo[d]oxazole is a promising candidate for tyrosinase inhibition.

Effects of green extraction methods on the chemical profile of Schisandra chinensis fruit extracts and on their tyrosinase inhibitory activity

The fruits of Schisandra chinensis (Turcz.) Baill. are a well-known food with health benefits for the central nervous system. This study was aimed at comparing green extracts of the fruits to select an environmentally friendly process providing a product rich in bioactives.S. chinensis fruits were extracted by decoction, macerations, ultrasound-assisted (UAE), and dynamic solid-liquid (SLDE) extraction using EtOH/H2O mixtures. The extract's chemical profiles were established by an integrated LC-MS and NMR approach. The LC-MS analysis revealed the presence of 70 metabolites, some of which never reported before in S. chinensis fruits, and the NMR analysis highlighted the occurrence of both primary and specialized metabolites. LC-MS and NMR data were processed by multivariate statistical analysis to highlight differences in the extraction methods. The extracts obtained with 100% EtOH by UAE and SLDE resulted the richest ones in lignans. Furthermore, the tyrosinase inhibitory activity of the extracts was tested (IC50 range 122.6–181.4 μg/ml). The extracts obtained with 100% EtOH showed the highest tyrosinase inhibitory activity, suggesting how the activity could be ascribed both to lignans, reported as responsible for the biological properties of S. chinensis and compounds as coumaric acid, 3,4,5-trimethoxycinnamic acid, gallic acid, known as tyrosinase inhibitors.

Stability, release, and tyrosinase inhibition behaviors of kojic acid encapsulated in the interlayer space of layered yttrium hydroxide

Kojic acid (KA) is widely utilized in cosmetic formulations for skin brightening and as a food preservative to prevent oxidative browning in fruits and vegetables. However, its effectiveness is compromised by susceptibility to pH and temperature fluctuations, as well as oxidation after exposure to UV light. These limitations highlight the need for improvements to facilitate sustainable applications. In this study, KA was encapsulated within the interlayer space of layered yttrium hydroxide (LYH) through a two-step host-guest reaction involving dodecylsulfate and basic ethoxide anions. Examination of the X-ray diffraction (XRD) pattern of the resulting product (KA-LYH) revealed an expanded interlayer space from approximately 8.4 to 16.7 Å, conducive to a partially interdigitated bilayer arrangement of KA anions within the LYH interlayer. KA-LYH demonstrated significantly improved stability against light, heat, and oxygen compared to free KA, indicating effective confinement and protection of KA from photoreaction and oxidation in the interlayer space of LYH host. Minimal release of KA was observed in saline solution and simulated seawater, while sustained release occurred in a phosphate buffer solution even after 24 h. Notably, the KA released from the LYH interlayer space retained potent tyrosinase inhibition activity, showcasing the sustainable efficacy of KA-LYH under physiological conditions.

Rutin of Moringa oleifera as a potential inhibitor to Agaricus bisporus tyrosinase as revealed from the molecular dynamics of inhibition

Tyrosinase is a binuclear copper-containing enzyme that catalyzes the conversation of monophenols to diphenols via o-hydroxylation and then the oxidation of o-diphenols to o-quinones which is profoundly linked to eukaryotic melanin synthesis and fruits browning. The hyperpigmentation due to unusual tyrosinase activity has gained growing health concern. Plants and their metabolites are considered promising and effective sources for potent antityrosinase enzymes. Hence, searching for potent, specific tyrosinase inhibitor from different plant extracts is an alternative approach in regulating overproduction of tyrosinase. Among the tested extracts, the hydro-alcoholic extract of Moringa oleifera L. leaves displayed the potent anti-tyrosinase activity (IC50 = 98.93 µg/ml) in a dose-dependent manner using L-DOPA as substrate; however, the kojic acid showed IC50 of 88.92 µg/ml. The tyrosinase-diphenolase (TYR-Di) kinetic analysis revealed mixed inhibition type for the Ocimum basilicum L. and Artemisia annua L. extracts, while the Coriandrum sativum L. extract displayed a non-competitive type of inhibition. Interestingly, the extract of Moringa oleifera L. leaves exhibited a competitive inhibition, low inhibition constant of free enzyme (Kiiapp\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\ ext{K}}_{\ ext{ii}}^{\ ext{app}}$$\\end{document}) value and no Pan-Assay Interfering Substances, hinting the presence of strong potent inhibitors. The major putative antityrosinase compound in the extract was resolved, and chemically identified as rutin based on various spectroscopic analyses using UV–Vis, FTIR, mass spectrometry, and 1H NMR. The in silico computational molecular docking has been performed using rutin and A. bisporus tyrosinase (PDB code: 2Y9X). The binding energy of the predicted interaction between tropolone native ligand, kojic acid, and rutin against 2Y9X was respectively − 5.28, − 4.69, and − 7.75 kcal/mol. The docking simulation results revealed the reliable binding of rutin to the amino acid residues (ASN260, HIS259, SER282) in the tyrosinase catalytic site. Based on the developed results, rutin extracted from M. oleifera L. leaves has the capability to be powerful anti-pigment agent with a potential application in cosmeceutical area. In vivo studies are required to unravel the safety and efficiency of rutin as antityrosinase compound.

Anti-biofilm properties of Portuguese honeys against multi-drug resistant microorganisms: A promising strategy for chronic wounds healing

Honey is considered a promising strategy for chronic wound management, being a possible solution for bacterial resistance problem mostly due to its physical-chemical features. However, these properties might vary significantly depending on the honey floral source. Dark-colored honey, such as chestnut honey, is related to increased antioxidant and bactericidal properties. This study aims to assess biofilms of multidrug-resistant microorganisms in honey samples from the Natural Park of Montesinho, in Portugal, which is considered a region with predominant chestnut floral source. The minimum inhibition concentration (MIC) of honey was tested for Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans. The biofilm removal as well as the metabolic inactivation of the biofilms were evaluated using three honey concentrations: 1xMIC, 5xMIC, and 10xMIC. The biofilm viability was analyzed with fluorescent microscopy. Honey samples were characterized according to the pollen profile, phenolic composition, H2O2 levels, tyrosinase inhibition, and pH. The antioxidant capacity was determined through FRAP and ABTS assays. Most of the honey samples exhibited a MIC of 6.75%. Biofilm removal efficacy differs among samples. Regression analysis evidenced a positive correlation between the biofilm removal and concentrations of H2O2, vanillic acid, pinocembrin, Cytisus striatus and Corrigiola telephiifolia, and pH. The honey concentration of 10xMIC was the most effective to inhibit the biofilm metabolism and viability. The concentrations of C. sativa, H2O2, and the anti-tyrosinase and FRAP activities were also positively correlated. The honey samples had a dominant presence of Castanea sativa pollen and were effective against biofilms formed by multidrug-resistant microorganisms.

Chemometric assisted green extraction of tyrosinase inhibitor from Durio zibethinus rind for skin whitening agents in cosmetic products

Cosmetics typically contain artificial substances that could be harmful to people's health. Extended usage and exposure to these harmful substances are frequently linked to a number of negative impacts and illnesses. This study processed a Durio zibethinus rind, rich in natural antityrosinase properties, with a chemometric-assisted green extraction system. The TPC value was obtained at the optimum conditions (34.4 MPa, 62°C, and 86 min). GC-MS and FTIR spectroscopy were performed to identify the phenolic compounds and their functional group, respectively. The optimized extract contains 77 % of the mushroom tyrosinase activity. PCA shows that aspidospermidin-17-ol,1-acetyl-19,21-apoxy-15,16-dimethoxy- (AP) resembles the similar cluster with hydroquinone. COSMO-RS was used to investigate the extraction mechanism of CO2 and AP during the SFE process. DFT and molecular docking were used to calculate the chemical reactivity and explain the tyrosinase inhibition mechanism, respectively. ADME-Tox and OSIRIS Property Explorer showed no violation of Lipinski’s rule, and toxicity with AP. In conclusion, a high-value, natural and safe cosmetic ingredient (AP) for cosmetopea was discovered using an innovative green extraction system.

Fast Screening of Tyrosinase Inhibitors in Coreopsis tinctoria Nutt. by Ligand Fishing Based on Paper-Immobilized Tyrosinase.

Coreopsis tinctoria Nutt. is an important medicinal plant in traditional Uyghur medicine. The skin-lightening potential of the flower has been recognized recently; however, the active compounds responsible for that are not clear. In this work, tyrosinase, a target protein for regulating melanin synthesis, was immobilized on the Whatman paper for the first time to screen skin-lightening compounds present in the flower. Quercetagetin-7-O-glucoside (1), marein (2), and okanin (3) were found to be the enzyme inhibitors. The IC50 values of quercetagetin-7-O-glucoside (1) and okanin (3) were 79.06 ± 1.08 μM and 30.25 ± 1.11 μM, respectively, which is smaller than 100.21 ± 0.11 μM of the positive control kojic acid. Enzyme kinetic analysis and molecular docking were carried out to investigate their inhibition mechanism. Although marein (2) showed a weak inhibition effect in vitro, it inhibited the intracellular tyrosinase activity and diminished melanin production in melanoma B16 cells as did the other two inhibitors. The paper-based ligand fishing method developed in this work makes it effective to quickly screen tyrosinase inhibitors from natural products. This is the first report on the tyrosinase inhibitory effect of those three compounds, showing the promising potential of Coreopsis tinctoria for the development of herbal skin-lightening products.

Valorization of hydro-distillate of fruit peels of Citrus paradisi macfad. Cultivar. Foster: Chemical profiling, antioxidant evaluation and in vitro and in silico enzyme inhibition studies

The major commercial crops in Pakistan are citrus fruit trees, which are farmed extensively and serve as the country's principal source of foreign exchange. A local citrus plant, Citrus paradisi, variety Foster is famous for its valuable fruit and fruit juice, however, tons of peels of this fruit are thrown as waste, which otherwise can be utilized in formulating nutraceutical and cosmetics. In the present study, essential oil of fruit peels was obtained through hydro-distillation, which was then analyzed through GC-MS analysis and studied for its antioxidant and enzyme inhibition potential. GCMS analysis revealed the presence of several components; major were found to be limonene, α-terpineol, caryophyllene, δ-amorphene, elemol, γ-eudesoml, nootkatone and di-isooctyl phthalate. Although, the oil showed weak free radical inhibition, it was potentially active in CUPRAC, FRAP, phosphomolybdenum and metal chelating antioxidant assays. The oil also exhibited anti-glucosidase, anti-amylase activities and also exhibited potent inhibition of the enzyme tyrosinase, which makes it strong candidate for nutraceuticals and skin care products. The docking studies also substantiate our results and caryophyllene, γ-eudesoml and nootkatone showed good binding affinity α-glucosidase and α-amylase and all tested compounds showed the higher binding affinity towards the enzyme tyrosinase.

Hematoxylin, an Alternative Substrate of Tyrosinase.

Mushroom tyrosinase from Agaricus bisporus (abTYR) is often used during the development of tyrosinase inhibitors for medicinal and cosmetic purposes. In the search for novel tyrosinase inhibitors, this study identified hematoxylin as an alternative substrate for abTYR. The interaction of hematoxylin with abTYR was investigated through spectrophotometric and chromatographic analyses. The results showed that hematoxylin acted as an abTYR substrate and exhibited Michaelis-Menten kinetic behaviour at concentrations below 1.25 mM. The substrate properties of hematoxylin were similar to the natural tyrosinase substrate, L-3,4-dihydroxyphenylalanine (L-DOPA), with regards to Km, while Vmax was eightfold lower. The main oxidation product formed during the reaction of abTYR with hematoxylin was identified as hematein. This is the first report of the interaction of hematoxylin with abTYR.

ESSENTIAL OIL CONTENTS AND BIOLOGICAL ACTIVITIES OF THYMUS CANOVIRIDIS JALAS AND THYMUS SIPYLEUS BOISS.

Objective: Members of the Lamiaceae family are considered to be major sources of bioactive therapeutic agents. Many of them are important medicinal and aromatic plants used in traditional and modern medicine and in the food, cosmetic and pharmaceutical industries. The aim of this study was to investigate in detail the biological activities and chemical composition of the essential oils of Thymus canoviridis Jalas and Thymus sipyleus Boiss. species belonging to the genus Thymus, one of the most important genera of the Lamiaceae family. Material and Method: The essential oil content of the species was determined by GC-MS. Antioxidant activities of the essential oils were determined using lipid peroxidation, DPPH free radical, ABTS cation radical and CUPRAC methods. In addition, cytotoxic activities against breast cancer (MCF-7) and colon cancer (HT-29) cell lines and anticholinesterase (against AChE and BChE enzymes), urease, tyrosinase, elastase, collagenase and angiotensin converting enzyme inhibition activities were determined. Result and Discussion: When the essential oil composition of T. sipyleus was analyzed, the major compounds were 1,8-cineole (eucalyptol) (18.16%), camphor (15.08%) and endo-borneol (11.63%), while T. canoviridis was found to be rich in carvacrol (72.88%). T. canoviridis showed high antioxidant activity in lipid peroxidation (IC50: 45.72±0.12 μg/ml), ABTS (IC50: 6.12±0.03 μg/ml) and CUPRAC (IC50: 5.31±0.01 μg/ml) methods. The selectivities of T. canoviridis and T. sipyleus species against MCF-7 cell line were 4.39 and 6.81, respectively. In the enzyme inhibition studies, both Thymus species showed moderate inhibition activity against BChE enzyme (Inhibition%: 57.88±1.14, 39.21±0.89, respectively). In addition, T. sipyleus showed moderate inhibition of elastase enzyme (Inhibition%: 25.33±0.79). When the results are evaluated in general, it can be said that T. canoviridis essential oil with its rich carvacrol content and high cytotoxic and antioxidant activity can be preferred as a safer and natural option instead of synthetic preservatives in food, pharmaceutical and cosmetic industries to extend shelf life and ensure food safety.

Synthesis, in vitro, and in silico study of novel pyridine based 1,3-diphenylurea derivatives as tyrosinase inhibitors

Tyrosinase inhibitors are studied in the cosmetics and pharmaceutical sectors as tyrosinase enzyme is involved in the biosynthesis and regulation of melanin, hence these inhibitors are beneficial for the management of melanogenesis and hyperpigmentation-related disorders. In the current work, a novel series of diphenyl urea derivatives containing a halo-pyridine moiety (5a–t) was synthesized via a multi-step synthesis. In vitro, tyrosinase inhibitory assay results showed that, except for two compounds, the derivatives were excellent inhibitors of human tyrosinase. The average IC50 value of the inhibitors (15.78 μM) is lower than that of kojic acid (17.3 μM) used as the reference compound, indicating that, on average, these molecules are more potent than the reference. Derivative 5a was identified as the most potent human tyrosinase inhibitor of the series, with an IC50 value of 3.5 ± 1.2 μM, approximately 5 times more potent than kojic acid. To get further insights into the nature of binding site interactions, molecular docking and molecular dynamics simulation studies were carried out. Moreover, the evaluation of in silico ADME properties showed a highly favorable profile for the synthesized compounds. These findings suggested that the further development of this class of compounds could be useful to get potent drug-like compounds that can target hyperpigmentation-related disorders.

Kinetic studies, molecular docking, and antioxidant activity of novel 1,3-diphenyl pyrazole-thiosemicarbazone with anti-tyrosinase and anti-melanogenesis properties

This study reports the Design Hypothesis of a novel series of 1,3-diphenyl pyrazole-thiosemicarbazone as novel tyrosinase inhibitors (TYRI). The designed compounds were prepared and their TYRI activity and mechanisms were studied. The results showed that the selected compounds exhibited potent tyrosinase inhibitory activities greater than that of kojic acid (KA). Lead candidates, denoted as 6g and 6n, with a para-hydroxyphenyl group attached to the 3-position of the pyrazole ring demonstrated IC50 values of 2.09 and 3.18 µM, respectively. The potency of these compounds was approximately 5–8 times higher than that of KA. The in vitro melanin content of 6g or 6n-treated melanoma cells resulted in significant efficacy in melanin reduction. The DPPH assay result revealed that the tyrosinase inhibition mechanism for these derivatives was independent of a redox effect and corresponded to the interaction with tyrosinase. According to the Lineweaver-Burk plot, the most potent compounds, 6g and 6n, exhibit a mixed type of inhibition, primarily noncompetitive inhibition. In silico molecular docking studies were employed to determine the binding mode and explore the Design Hypothesis in detail. The results suggested that these compounds could be considered promising leads for the further development of novel inhibitors to treat disorders related to tyrosinase.

FORMULATION OF NANOSTRUCTURED LIPID CARRIER GEL FROM CALLUS EXTRACT OF MULBERRY LEAF (MORUS ALBA L.) WITH 2, 4-DICHLORO PHENOXY ACETIC ACID AND BENZYL AMINO PURINE AS CALLUS GROWTH FACTOR

Objective: This research aimed to formulate the callus extract of mulberry leaf in the form of a Nanostructured lipid Carrier (NLC) gel. Methods: Dichlorophenoxyacetic acid (2,4–D) and Benzyl Amino Purine (BAP) was used as a callus growth factor. Callus leaf extracted with ethanol 96% by maceration-sonication method. An amount of 0.5% callus leaf extract was formulated into NLC. The NLC is then evaluated for its particle size and polydispersity index. The NLC gel is evaluated for its organoleptic, homogeneity, viscosity, flow ability, and pH. The callus extract and the NLC gel were also evaluated for their tyrosinase inhibitor activity. Results: The best formulation of NLC showed a particle size of 189.8 nm and a polydispersity index of 0.578. The NLC is a semi-solid, yellowish, odorless, homogeneous gel, with viscosity of 26,666.67 cPs, plastic-thixotropic type, pH of 5.26. The evaluation of tyrosinase inhibitory activity of the callus extract and the NLC gel showed IC50 value of 217.64 and 248.12 ug/ml. Conclusion: It can be concluded that leaf callus extract of mulberry can be formulated into an NLC gel that is physically and chemically stable and has good skin-lightening activity.

Skin Health and Complexion Improvement Benefits of Selected Ayurvedic Medicinal Plants

Skin health and complexion improvement have become more prioritized and the need for natural remedies are more in demand than the synthetic options. Research in the area of skin care is growing with regular updation of facts and data. In Ayurveda, skin complexion improvement is comparable to the modern concepts such as tyrosinase inhibition and anti-oxidant activity. In this review, selected Ayurvedic medicinal plants are screened from classical Ayurvedic texts as well as the modern scientific literature to investigate their probable potential for skin health and skin lightening effects. All the plants reviewed are found to act as complexion promoters directly or indirectly by their interference in melanogenesis pathway or through antioxidant potentials. This efficiently confirms the goodness of these plants as potential skin care and whitening agents.

Anti-Skin Aging and Cytotoxic Effects of Methanol-Extracted Solanum betaceum Red Fruit Seed Extract on Ca9-22 Gingival Carcinoma Cells.

The tamarillo, or Solanum betaceum, recognized for its comprehensive nutritional profile, has long been valued for its diverse ethnobotanical uses. This study delves into the potential therapeutic applications of S. betaceum by analyzing its polyphenolic content (TPC), total flavonoid content (TFC), anti-skin aging activities against key enzymes like elastase, tyrosinase, and hyaluronidase, and its cytotoxic effects on oral carcinoma cells. Extracts from the seeds, pulp, and peel of red and yellow fruits were prepared using methanol, ethanol, and acetone. The highest TPC was found in the methanol extract from red fruit seeds (9.89 mg GAE/g), and the highest TFC was found in the methanol extract of yellow fruit peel (3.02 mg QUE/g). Some of these extracts significantly inhibited skin aging-associated enzymes with the red fruit seed extract (100 μg/mL) showing up to 50.4% inhibition of tyrosinase. Additionally, the red fruit seed extract obtained using methanol demonstrated potential anticancer effects against Ca9-22 oral carcinoma cells by inhibiting cell survival, migration, and proliferation as well as inducing apoptosis. These results underscore the potential of S. betaceum fruit extracts, especially from red fruit seeds, as promising agents for anti-skin aging and anticancer applications, meriting further exploration for therapeutic uses.

Melanin Synthesis Gene Inhibition Effect through Inhibition of Tyrosinase and TRPs Expression of Coriandrum sativum-derived Exosome

Purpose: This study investigated the skin-whitening effects achieved through suppressing melanin synthesis using exosomes derived from Coriandrum sativum (C. sativum). Methods: We examined the characteristics of C. sativum exosomes (CSEs) using nanoparticle tracking analysis, which revealed an average size of 152.3 nm and a concentration of 3.0×1010 particles/mL. A cytotoxicity evaluation was conducted on B16F0 cells to assess cellular safety of CSEs. We investigated the skin-whitening effects of CSEs by quantifying melanin synthesis gene expression using RT-PCR. Results: CSE concentrations less than 1.5 × 108 particles/mL did not negatively affect cellular activity. Furthermore, CSE treatment significantly decreased the expression of key genes involved in melanin synthesis such as tyrosinase, TRP-1, and TRP-2 by 75.6%, 89.1%, and 88.7%, respectively. Conclusion: CSEs hold promise as functional cosmetic ingredients that promote skin whitening by inhibiting key genes involved in melanin production.

Anti-Skin Aging Potential, Antibacterial Activity, Inhibition of Single-Stranded DNA-Binding Protein, and Cytotoxic Effects of Acetone-Extracted Passiflora edulis (Tainung No. 1) Rind Extract on Oral Carcinoma Cells.

The passion fruit, Passiflora edulis, recognized for its rich nutritional properties, has long been used for its varied ethnobotanical applications. This study investigates the therapeutic potential of P. edulis var. Tainung No. 1 rind extracts by examining their polyphenolic content (TPC), total flavonoid content (TFC), anti-skin aging activities against key enzymes such as elastase, tyrosinase, and hyaluronidase, and their ability to inhibit bacterial growth, single-stranded DNA-binding protein (SSB), and their cytotoxic effects on oral carcinoma cells. The acetone extract from the rind exhibited the highest levels of TPC, TFC, anti-SSB, and antibacterial activities. The antibacterial effectiveness of the acetone-extracted rind was ranked as follows: Escherichia coli > Pseudomonas aeruginosa > Staphylococcus aureus. A titration curve for SSB inhibition showed an IC50 value of 313.2 μg/mL, indicating the potency of the acetone extract in inhibiting SSB. It also significantly reduced the activity of enzymes associated with skin aging, particularly tyrosinase, with a 54.5% inhibition at a concentration of 100 μg/mL. Gas chromatography-mass spectrometry (GC-MS) analysis tentatively identified several major bioactive compounds in the acetone extract, including stigmast-5-en-3-ol, vitamin E, palmitic acid, stigmasterol, linoleic acid, campesterol, and octadecanoic acid. Molecular docking studies suggested some of these compounds as potential inhibitors of tyrosinase and SSB. Furthermore, the extract demonstrated anticancer potential against Ca9-22 oral carcinoma cells by inhibiting cell survival, migration, and proliferation and inducing apoptosis. These results underscore the potential of P. edulis (Tainung No. 1) rind as a promising candidate for anti-skin aging, antibacterial, and anticancer applications, meriting further therapeutic investigation.

In Silico Identification and Molecular Mechanism of Novel Tyrosinase Inhibitory Peptides Derived from Nacre of Pinctada martensii.

Pearl and nacre powders have been valuable traditional Chinese medicines with whitening properties for thousands of years. We utilized a high-temperature and high-pressure method along with compound enzyme digestion to prepare the enzymatic hydrolysates of nacre powder of Pinctada martensii (NP-PMH). The peptides were identified using LC-MS/MS and screened through molecular docking and molecular dynamics simulations. The interactions between peptides and tyrosinase were elucidated through enzyme kinetics, circular dichroism spectropolarimetry, and isothermal titration calorimetry. Additionally, their inhibitory effects on B16F10 cells were explored. The results showed that a tyrosinase-inhibitory peptide (Ala-His-Tyr-Tyr-Asp, AHYYD) was identified, which inhibited tyrosinase with an IC50 value of 2.012 ± 0.088 mM. The results of the in vitro interactions showed that AHYYD exhibited a mixed-type inhibition of tyrosinase and also led to a more compact enzyme structure. The binding reactions of AHYYD with tyrosinase were spontaneous, leading to the formation of a new set of binding sites on the tyrosinase. The B16F10 cell-whitening assay revealed that AHYYD could reduce the melanin content of the cells by directly inhibiting the activity of intracellular tyrosinase. Additionally, it indirectly affects melanin production by acting as an antioxidant. These results suggest that AHYYD could be widely used as a tyrosinase inhibitor in whitening foods and pharmaceuticals.

Inhibitory Effects, Fluorescence Studies, and Molecular Docking Analysis of Some Novel Pyridine-Based Compounds on Mushroom Tyrosinase.

Melanin biosynthesis in different organisms is performed by a tyrosinase action. Excessive enzyme activity and pigment accumulation result in different diseases and disorders including skin cancers, blemishes, and darkening. In fruits and vegetables, it causes unwanted browning of these products and reduces their appearance quality and economic value. Inhibiting enzyme activity and finding novel powerful and safe inhibitors are highly important in agriculture, food, medical, and pharmaceutical industries. In this regard, in the present study, some novel synthetic pyridine-based compounds including 2,6-bis (tosyloxymethyl) pyridine (compound 3), 2,6-bis (butylthiomethyl) pyridine (compound 4), and 2,6-bis (phenylthiomethyl) pyridine (compound 5) were synthesized for the first time, and their inhibitory potencies were assessed on mushroom tyrosinase diphenolase activity. The results showed that while all tested compounds significantly decreased the enzyme activity, compounds 4 and 5 had the highest inhibitory effects (respectively, 80 and 89% inhibition with the IC50 values of 17.0 and 9.0 μmol L-1), and the inhibition mechanism was mixed-type for both compounds. Ligand-binding studies were carried out by fluorescence quenching and molecular docking methods to investigate the enzyme-compound interactions. Fluorescence quenching results revealed that the compounds can form nonfluorescent complexes with the enzyme and result in quenching of its intrinsic emission by the static process. Molecular docking analyses predicted the binding positions and the amino acid residues involved in the interactions. These compounds appear to be suitable candidates for more studies on tyrosinase inhibition.

Chemical composition and bioactivity of essential oils from Cistus ladanifer L., Pistacia lentiscus L., and Matricaria chamomilla L

The objective of this study was to characterize the volatile compounds from the aerial part of Cistus ladanifer L., Pistacia lentiscus L., and Matricaria chamomilla L., members of Cistaceae, Anacardiaceae, and Asteraceae families, respectively; and assess their potential antioxidant, antimicrobial, and enzyme inhibitory properties. The essential oils were analyzed using gas chromatography-mass spectrometry (GC-MS-MS) analysis. The outcomes revealed distinct chemical profiles indicative of specific chemotypes within each species. Indeed, M. chamomilla essential oil (MCEO) contained sabinene (16.03 %), camphor (11.22 %), 3,6-dihydrochamazulene (14.22 %), and chamazulene (12.84 %) as its primary constituents. C. ladanifer essential oil (CLEO) prominently featured camphene (31.5 %), α-pinene (15.76%), and bornyl acetate (15.73 %), while P. lentiscus essential oil (PLEO) was rich in D-limonene (21 %), β-myrcene (14.89 %), α-pinene (13.93 %), and terpinen-4-ol (9.75 %). Remarkably, PLEO exhibited significant antioxidant activity across multiple assays, demonstrating inhibitory values of 72.07 ± 4.06 mg TE/g of extract (Cuprac), 45.74 ± 1.23 mg TE/g of extract (FRAP), 30.89 ± 1.69 mg EDTAE/g of extract (Chelating), 26.71 ± 1.84 mmol TE/g of extract (Phosphomolybdenum), 15.55 ± 0.84 mg TE/g of extract (ABTS), and 2.30 ± 0.22 mg TE/g of extract (DPPH). The results showed that the microorganisms under examination varied in their sensitivity to essential oils and the inhibitory zone ranged between 25 and 57 mm. The inhibitory effects of the essential oils were investigated against enzymes associated with human pathologies. As findings, CLEO demonstrated substantial inhibition of tyrosinase (10.22 ± 0.13 mg KAE/g of extract) and acetylcholinesterase (4.71 ± 0.97 mg GALAE/g of extract), outperforming other essential oils that displayed moderate activities. These important biological effects of the oils tested qualify these plants as an interesting source of phytochemicals with medicinal actions.