Strong Tyrosinase Inhibitory Activity Research Articles

Characterization, antibacterial, antioxidant, antidiabetic, anti-inflammatory and antityrosinase activity of green synthesized silver nanoparticles using Calophyllum tomentosum leaves extract

Abstract The current research study is to develop an easy and eco-friendly method for the synthesis of AgNPs using aqueous leaf extract of Calophyllum tomentosum (CtAgNPs) and evaluated the extract to know the effects of anti-bacterial, antioxidant, anti-diabetic, anti-inflammatory and anti-tyrosinase activity. Using UV–vis spectrophotometer, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX) characterized the Calophyllum tomentosum mediated silver nanoparticles. The leaf extract of C. tomentosum yielded flavonoids, saponins, tannins, alkaloids, glycosides, phenols, terpenoids and coumarins. AgNPs formation was confirmed by UV–vis spectra at 438 nm. Crystalline structure with a face centered cubic (fcc) of AgNPs was observed in XRD. FTIR had shown that the phytochemicals were responsible for the reduction and capping material of silver nanoparticles. The size and shape of the AgNPs were determined using SEM. From EDX study analysed the strong absorption property of AgNPs. The CtAgNPs have showed significant antibacterial activity on multi drug resistance bacteria. The CtAgNPs had shown strong antioxidant (DPPH, H2O2 scavenging, nitric oxide scavenging power, reducing power) activities. The CtAgNPs had strongly inhibited the α-glucosidase and DPPIV compared to α-amylase. The CtAgNPs exhibited strong anti-inflammatory activity (albumin denaturation, membrane stabilization, heat haemolytic, protein inhibitory, lipoxygenase, xanthine oxidase) and tyrosinase inhibitory activity. To our best knowledge, this is the first attempt on the synthesis of silver nanoparticles using Calophyllum tomentosum leaves extract. Hence, to validate our results the in vivo studies at molecular level are needed to develop an antioxidant, anti-diabetic and anti-inflammatory agent.

Isolation of proanthocyanidins from red wine, and their inhibitory effects on melanin synthesis in vitro

The red wines made from Vitis vinifera were identified as skin-whitening effectors by using in vitro assays. OPCs in the wine were evaluated for tyrosinase activity and melanogenesis. Strong tyrosinase inhibitory activity was observed in fractions with high oligomeric proanthocyanidin (OPC) content. Among OPC dimers, a strong inhibitory effect on tyrosinase was observed with OPCs which contain (+)-catechin as an upper unit. Melanogenesis inhibitory effect was observed with OPCs which have (-)-epicatechin as upper units. Also, OPC trimers, upper and middle units joined with 4 → 8 bonds, showed stronger effects compared to trimers with 4 → 6 linkages. Interestingly, (-)-epicatechin-(4β → 8)-(-)-epicatechin 3-O-gallate, which is a unique component of grapes has potent inhibitory effects on both tyrosinase and melanogenesis. Our data provide structural information about such active compounds. These results suggest that red wines containing OPC, have high melanogenesis inhibitory effect and are supposed to have skin-whitening effect.

Novel Multifunctional Hydroxypyridinone Derivatives as Potential Shrimp Preservatives

In order to develop a new efficient method for the prolongation of shrimp shelf life, two novel hydroxypyridinone derivatives ((S)-2-amino-N-((S)-1-(((5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl)amino)-1-oxo-3-phenylpropan-2-yl)-3-phenylpropanamide (2) and (S)-(5-hydroxy-4-oxo-1,4-dihydropyridin-2-yl)methyl 2-(benzyloxycarbonyl)-3- phenylpropanoate (3)) possessing strong tyrosinase inhibitory activity were investigated to explore their potential as shrimp preservatives. Their antimicrobial activities were evaluated by a disk diffusion method. Inhibition zone assays indicated that both 2 and 3 possess a stronger inhibitory effect than kojic acid. The minimum inhibition concentrations (MICs) of compound 3 against Bacillus subtilis, Staphylococcous aureus, Escherichia coli, Salmonella spp., and Pseudomonas aeruginosa were determined to be 32, 32, 32, 8, and 16 μg/mL. Both 2 and 3 were also found to possess antioxidant activity. The IC50 values of 2 and 3 for scavenging DPPH radical were measured to be 2.93 and 2.37 mg/mL, respectively. At 4 mg/mL, 2 and 3 were determined to have total antioxidant capacity of 2.43 and 2.72 U/mL, respectively. Compound 3 was further investigated for efficacy in shrimp preservation by sensory evaluation, determination of total volatile basic nitrogen (TVB-N), pH, and total bacterial count. The treatment with 3 was found to extend the shelf life of Penaeus vannamei Boone to 10 days at 4 °C, while the shelf life of shrimp treated with 4-hexylresorcinol, kojic acid, and the control group was 9, 6, and 4 days, respectively. Compound 3 could find application in the food industry, as a shrimp preservative, due to its protective properties.

Cellular Anti-Melanogenic Effects of a Euryale ferox Seed Extract Ethyl Acetate Fraction via the Lysosomal Degradation Machinery.

The aim of this study was to investigate the effect of ethyl acetate fraction of Euryale ferox seed extracts (Efse-EA) on melanogenesis in immortalized mouse melanocyte cell line, melan-a. Efse-EA showed strong dose-dependent mushroom tyrosinase inhibitory activity. Treatment of melan-a cells with 30 μg/mL Efse-EA produced strong inhibition of cellular tyrosinase and melanin synthesis. Efse-EA significantly reduced the levels of melanogenesis-related proteins, such as tyrosinase, tyrosinase-related proteins 1 and 2, and microphthalmia-associated transcription factor. Because Efse-EA treatment reduced tyrosinase protein levels without changing its mRNA expression, we investigated whether this decrease was related to proteasomal or lysosomal degradation of tyrosinase. We found that chloroquine, a lysosomal proteolysis inhibitor, almost completely abolished both the down-regulation of tyrosinase and the inhibition of melanin synthesis induced by Efse-EA. These results suggested that Efse-EA may contribute to the inhibition of melanogenesis by altering lysosomal degradation of tyrosinase, and that this extract may provide a new cosmetic skin-whitening agent.

Preparation, Characterization, and Preliminary Antibrowning Evaluations of Norartocarpetin Microemulsions

Norartocarpetin is a flavone widely distributed in Moraceae plants with strong tyrosinase inhibitory activity. However, its poor solubility in aqueous systems and in food grade solvents (oils) limits its extensive applications. The aim of this study was to improve the solubility of norartocarpetin by developing an oil-in-water (o/w) microemulsion with food grade components. A microemulsion was developed and characterized, and its chemical and physical stabilities were also evaluated within 8 weeks. Using the construction of pseudoternary phase diagrams, the optimized formulation of 2% w/w of ethyl oleate, 12% w/w of Tween 80, 6% w/w of polyethylene glycol 400, and 80% w/w of water was obtained, with a maximum solubility of norartocarpetin up to 1.73 ± 0.21 mg/mL, at least a 1000-fold increase in solubility. The microemulsion base and norartocarpetin-loaded microemulsion were demonstrated to be stable after accelerated and long-term conditions (8 weeks). The norartocarpetin microemulsion still showed strong tyrosinase inhibitory activity and antibrowning effect on fresh-cut apple slices. These combined results indicated that norartocarpetin microemulsion may be suitable as an antibrowning agent for fresh-cut fruits.

New tyrosinase inhibitors from Paecilomyces gunnii.

Through screening 50 strains of entomopathogenic fungi and rescreening of 7 strains of Paecilomyces gunnii, a methanol extract of liquid-cultivated mycelia of P. gunnii was found to have the strongest tyrosinase inhibitory activity. Preparative high-speed counter-current chromatography (HSCCC) guided by high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-high-resolution mass spectrometry (HRMS) was employed for the isolation and purification of the active components, and three new compounds with half inhibition concentration (IC50) of 0.11, 0.17, and 0.14 mM against diphenolase were obtained from the extract, respectively. Their chemical structures were identified by HRMS, one- and two-dimensional nuclear magnetic resonance (2D NMR) spectroscopy as paecilomycones A, B, and C. Structure and activity studies showed that the tyrosinase inhibition activities are positively related to the number of hydroxyl groups on the paecilomycones.

Tyrosinase inhibitory activity of supernatant and semi-purified extracts from squid pen fermented with Burkholderia cepacia TKU025

Reports of tyrosinase inhibitors from microorganisms are rare. The tyrosinase inhibitory activity was found from the culture supernatant of Burkholderia cepacia TKU025 with 1 % squid pen as the sole carbon/nitrogen source. The fourth-day supernatant showed the strongest tyrosinase inhibitory activity (500 U/ml) and the highest total phenolic content (789 μg/ml GAE). The supernatant was further purified by liquid–liquid partition, and it was found that the methanol extract exhibited the lowest IC50 value of 2 μg/ml in the tyrosinase inhibitory activity assay and was compared with the positive control kojic acid and vitamin C. Significant associations between the tyrosinase inhibitory potency and the total phenolic content were found for the supernatant, extract, and fractions. The tyrosinase inhibitory activity persisted even when it was treated with acidic or alkaline conditions of pH 2 or 12. The tyrosinase inhibitory activity remained at 100 %, even after treatment at 100 °C for 60 min. The tyrosinase inhibitor also showed antimicrobial activity against Escherichia coli, Bacillus cereus, Aspergillus fumigatus, and Fusarium oxysporum.

Characterization of tyrosinase inhibitors in the twigs of Cudrania tricuspidata and their structure–activity relationship study

The twigs of Cudrania tricuspidata were found to show strong tyrosinase inhibitory activity, and further detailed component analysis resulted in the isolation of a new flavanol glucoside, (2S,3S)-2,3-trans-dihydromorin-7-O-β-d-glucoside (1), plus twenty-seven known compounds (2–28). Their structures were elucidated on the basis of ESI-MS and NMR spectral data. Among the isolated compounds, trans-dihydromorin (8), oxyresveratrol (9), and steppogenin (12) were found to exhibit significant tyrosinase inhibition activities. Moreover, the structure–activity relationship of these isolated compounds was also discussed.

Dioscin: A synergistic tyrosinase inhibitor from the roots of Smilax china

In our study, we investigated the inhibition of mushroom tyrosinase in Smilax china. A methanol (MeOH) extract of S. china was partitioned into hexane, ethyl acetate (EtOAc) and water. Of the three fractions, EtOAc extract showed the strongest inhibition of tyrosinase activity with l-tyrosine or l-DOPA as a substrate. Two compounds were isolated from a final active fraction by activity-guided column chromatography. These compounds were identified as dioscin and oxyresveratrol by comparing their mass, (1)H- and (13)C-NMR spectral data with those reported in the literature. Dioscin showed little inhibition activity of tyrosinase, whereas oxyresveratrol, a known tyrosinase inhibitor, showed a strong tyrosinase inhibitory activity. We discovered that a mixture of oxyresveratrol and dioscin (IC(50)=5.1 and 5.7 μg/ml) highly increased the inhibition of tyrosinase activity with l-tyrosine or l-DOPA as the substrate as compared to either oxyresveratrol (IC(50)=7.8 and 10.9 μg/ml) or dioscin (IC(50)>100 and 100 μg/ml) alone.

Bioactive compounds, antioxidant, tyrosinase inhibition, xanthine oxidase inhibition, anticholinesterase and anti inflammatory activities of Prunus mahaleb L. seed

Prunus mahaleb L. plant is cultivated for its seeds which are known as a spice. There is lack of information about its biological activities although it has long history of ethnopharmacological application. Therefore, this research was conducted to evaluate the bioactive compounds, antioxidant, tyrosinase inhibition, xanthine oxidase (XO) inhibition, anticholinesterase and anti inflammatory activities of the P. mahaleb L. seeds. Results showed that the total phenolic and flavonoid compounds concentration in the methanolic extract were 75.7±0.18 and 28.5±0.37 mg/g dry weight (DW) whereas in the hexane extract were 34.6±0.24 and 16.2±0.31 mg/g dry weight, respectively. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity, ferric reducing antioxidant power (FRAP) activity and nitric oxide (NO) scavenging activity of the methanolic extract at the concentration of 100 µg/ml of crude extract were 44.3, 51.9 and 36.9% respectively, while for the hexane extract were 26.8, 32.8 and 21.8%, respectively. Both extracts showed antioxidant activity although they were lower than reference antioxidants (vitamin C, E and butylated hydroxyltoluene (BHT)). Ferric thiocyanate (FTC) and thiobarbituric acid (TBA) tests results showed the antioxidant activity of extracts. Methanolic extract in XO, tyrosinase, acetylthiocholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition assays showed the significant (p<0.05) lower IC50 with values of 59.8, 21.0, 52.1 and 86.2 µg/ml as compared to the hexane extract with the values of 94.1, 54.2, 85.2 and 110.7 µg/ml. Anti-inflammatory assay using LPS/IFN-γ stimulated RAW 264.7 cells indicated that methanolic extract is a potent source of anti-inflammatory agent. Consequently, the methanolic extracts of P. mahaleb seeds possess strong tyrosinase inhibitory activity and moderate antioxidant potential, XO inhibitory, anticholinesterase and anti inflammatory activities. Key words: Prunus mahaleb, phenolics, flavonoids, antioxidant, xanthine oxidase, tyrosinase, anticholinesterase, anti inflammatory.

Daedalin A, a Metabolite ofDaedalea dickinsii, Inhibits Melanin Synthesis in anin VitroHuman Skin Model

The culture broth of Daedalea dickinsii was found to predominantly contain the tyrosinase inhibitor, (2R)-6-hydroxy-2-hydroxymethyl-2-methyl-2H-chromene, daedalin A (1). Ongoing research into bioactive metabolites resulted in the identification of two new 2H-chromenes, 6-hydroxy-5,7-dimethoxy-2,2-dimethyl-2H-chromene (3) and 6-hydroxy-2-hydroxymethyl-5-methoxy-2-methyl-2H-chromene (4), together with 6-hydroxy-2,2-dimethyl-2H-chromene (2). Comparative studies of isolated compounds 1-4 and related compounds (+/-)-1 and 1a-1c showed 1 to have the strongest tyrosinase inhibitory activity. These results suggest that the hydroxyl groups at positions 6 and 9 of 1 were important for the potent activity. A Lineweaver-Burk plot for a kinetic analysis indicates that 1 competed with L-tyrosine for tyrosinase. Compound 1 also suppressed melanogenesis in a human skin model (up to 49% at 2.8 micromol/tissue application) without affecting the cell viability. Compounds 1, 1b and 1c also showed 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity comparable to that of alpha-tocopherol.

The Constituents and Their Bioactivities of Houttuynia cordata

Chemical investigation on the whole plant of Houttuynia cordata has resulted in the isolation of two new compounds, named as houttuynoside A (1) and houttuynamide A (2), together with thirty-eight known compounds. The structures of 1 and 2 were elucidated on the basis of spectroscopic analysis. In the inhibitory effects on herpes simplex virus type 1 (HSV-1) assay, norcepharadione B (10) showed good inhibitory activity against the replication of HSV-1. In addition, the antioxidant and antityrosinase activities of some isolated compounds were also evaluated. Among these compounds, quercitrin (25) and quercetin-3-O-beta-D-galactopyranoside (26) showed excellent 2,2-diphenyl-1-picrylhydrazyl radical-scavenging property with IC50 values of 31 and 63 microM, respectively. Cepharadione B (9) exhibited strong tyrosinase inhibitory activity with an IC50 value of 170 microM.

Isolation of tyrosinase inhibitors from Artocarpus heterophyllus and use of its extract as antibrowning agent

A new furanoflavone, 7-(2,4-dihydroxyphenyl)-4-hydroxy-2-(2-hydroxy propan-2-yl)-2, 3-dihydrofuro(3, 2-g)chromen-5-one (artocarpfuranol, 1), together with 14 known compounds, dihydromorin (2), steppogenin (3), norartocarpetin (4), artocarpanone (5), artocarpesin (6), artocarpin (7), cycloartocarpin (8), cycloartocarpesin (9), artocarpetin (10), brosimone I (11), cudraflavone B (12), carpachromene (13), isoartocarpesin (14), and cyanomaclurin (15) were isolated from the wood of Artocarpus heterophyllus. Their structures were identified by interpretation of MS,( 1)H-NMR,( 13)C-NMR, HMQC, and HMBC spectroscopic data. Among them, compounds 1-6 and 14 showed strong mushroom tyrosinase inhibitory activity with IC(50) values lower than 50 microM, more potent than kojic acid (IC(50) = 71.6 microM), a well-known tyrosinase inhibitor. In addition, extract of A. heterophyllus was evaluated for its antibrowning effect on fresh-cut apple slices. It was discovered that fresh-cut apple slices treated by dipping in solution of 0.03 or 0.05% of A. heterophyllus extract with 0.5% ascorbic acid did not undergo any substantial browning reaction after storage at room temperature for 24 h. The antibrowning effect was significantly better than samples treated with the extract (0.03 or 0.05%) or ascorbic acid (0.5%) alone. The results provide preliminary evidence supporting the potential of this natural extract as antibrowning agent in food systems.

Kurarinol, tyrosinase inhibitor isolated from the root of Sophora flavescens

It is well known that flavanones, sophoraflavanone G 1, kurarinone 2, and kurarinol 3, from the root of Sophora flavescens, have extremely strong tyrosinase inhibitory activity. This study delineates the principal pharmacological features of kurarinol 3 that lead to inhibition of the oxidation of l-tyrosine to melanin by mushroom tyrosinase (IC(50) of 100 nM). The inhibition kinetics analyses unveil that compounds 1 and 2 are noncompetitive inhibitors. However similar analysis shows kurarinol 3 to be a competitive inhibitor. Compounds 1 and 2 exhibited potent antibacterial activity with 10 microg/disk against Gram-positive bacteria, whereas kurarinol 3 did not ostend any antibacterial activity. Interestingly, kurarinol 3 inhibits production of melanin in S. bikiniensis without affecting the growth of microorganism. It is thus distinctly different from the other tyrosinase inhibitors 1 and 2. In addition, kurarinol 3 manifests relatively low cytotoxic activity (EC(50)>30 microM) compared to 1 and 2. To account for these observations, we conducted molecular modeling studies. These suggested that the lavandulyl group within 3 is instrumental in the interaction with the enzyme. More specifically, the terminal hydroxy function within the lavandulyl group is most important for optimal binding.

Isolation and Synthesis of Cosmetic Substances from African Dietary Leaves, Celosia argentea L. for Skin Depigmentation.

Six compounds were isolated from the leaves of Celosia argentea L.. Tyrosinase inhibitory and superoxide scavenging activity of the compounds was examined so as to obtain a skin depigmentation agent for cosmetic application. Eugenyl O-β-D-glucopyranoside (citrusin C, 1) showed strong tyrosinase inhibitory activity. Two-step inhibitory effects of successive tyrosine and DOPA oxidation for tyrosinase were stronger compared to arbutin used commercially at present (47.20% inhibition of tyrosine oxidation and 87.93%, DOPA oxidation, compared to 63.00% for tyrosine and 7.70% for DOPA oxidation in the case of arbutin). Moreover, we succeed in providing compound 1 abundantly in the synthetic study which used acetobromo-α-D-glucose and Sn(OTf)2.

Synthesis of Karahanaenone Derivatives and Their Inhibition Properties toward Tyrosinase and Superoxide Scavenging Activity†

Fourteen amides condensing with aminophenols, anisidines, or aniline were synthesized from karahanaenone 1 as the starting material. The tyrosinase inhibitory activity and superoxide scavenging activity of these derivatives were examined in order to develop whitening agents for cosmetics. Of the compounds, N-p-hydroxyphenyl-1,3,3,6-trimethyl-5-cyclohepten-2-on-1-carboxamide 9, 2-hydroxy-N-o-hydroxyphenyl-3,3,6-trimethyl-5-cyclohepten-1-carboxamide 13, and 2-hydroxy-N-p-hydroxyphenyl-3,3,6-trimethyl-5-cyclohepten-1-carboxamide 15 showed strong tyrosinase inhibitory activity. 13 and 5 possessed a hydroxy group in the karahana skeleton and on the aromatic ring, respectively. These inhibitory rates were higher than that of arbutin that is used for commercial cosmetics (77.4%, 73.6%, and 72.3% against 63.0% for arbutin). Furthermore, 13 indicated 51.0% for superoxide scavenging activity.