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1.
Langmuir ; 37(37): 10883-10889, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34498463

RESUMO

In living organisms, tyrosinase selectively produces l-DOPA from l-tyrosine. Here, a bicomponent hydrogel is used as a template for tyrosinase-catalyzed selective generation of l-DOPA from tyrosine. An amphiphilic molecule 1,5-diaminonaphthalene (DAN) coassembles with 1,3,5-benzenetricarboxylic acid (BTC) to form a self-supporting hydrogel. After alteration of complementary acids, DAN does not coassemble to form a hydrogel. The coassembly mechanism is investigated using spectroscopic techniques. The transmission electron microscopy and scanning electron microscopy images reveal the morphology details. The l-DOPA is kept from being oxidized when the hydrogel is used as a template. The enzymatically synthesized l-DOPA can also be separated from the mixture by easy tuning of the bicomponent coassembly.


Assuntos
Hidrogéis , Monofenol Mono-Oxigenase , Levodopa , Monofenol Mono-Oxigenase/metabolismo , Oxirredução , Tirosina
2.
Enzyme Microb Technol ; 150: 109884, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34489037

RESUMO

Tyrosinase plays an essential role in melanin biosynthesis and inherently exhibits both monophenolase and diphenolase activity. A first derivative synchronous fluorometric assay was established for directly monitoring monophenolase activity. The zero-crossing point at 322 nm for the first-derivative under synchronous fluorescence with Δλ = 67 nm was utilized to selectively quantify tyrosine in the presence of the reaction product dihydroxyphenylalanine (DOPA). The limit of detection (LOD) for tyrosine was 0.54 µM. The fluorescence intensity of tyrosine was monitored at intervals of 30 s to establish the time course of tyrosine consumption. The LOD for the monophenolase activity was 0.0706 U⋅ mL-1. The Michaelis-Menten e constant and maximum speed were 21.83 µM and 1.12 µM min-1, respectively. Zinc ions competitively inhibited the monophenolase activity, with an IC50 value of 14.36 µM. This assay is easily and rapidly executed and is of great significance for analyzing the kinetics of enzymatic reactions and in fundamental research on monophenolase. This approach has potential applications in the discovery of tyrosinase inhibitors for medicine and cosmetics, as well as in the industrial synthesis of substituted o-diphenol intermediates.


Assuntos
Monofenol Mono-Oxigenase , Oxirredutases , Monofenol Mono-Oxigenase/metabolismo , Oxirredução , Oxirredutases/metabolismo , Tirosina/metabolismo
3.
Life Sci ; 284: 119930, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34480938

RESUMO

AIMS: Silk fibroin (SF), a natural product from silkworms, has been used to promote anti-inflammation, induce wound healing, and reduce melanin production. However, the underlying regulatory mechanism of SF on melanin production remains unknown. The aim of this study was to investigate the distinct regulatory mechanism of SF in B16 melanoma cells by applying quantitative proteomic approach. MATERIALS AND METHODS: B16 melanoma cells were treated with PBS, KA or SF for 48 h, respectively. Cell viability, melanin content, and tyrosinase activity were examined. A label-free quantitative proteomic approach was utilized to investigate the regulatory mechanism of SF. The differentially expressed proteins and their related biological processes were subsequently identified by bioinformatics methods. Furthermore, the identified differentially expressed proteins were validated by western blot. KEY FINDINGS: Both SF and KA were able to suppress the melanin synthesis of B16 melanoma cells without appreciable toxicity; yet, SF had a distinct effect on mushroom tyrosinase activity in vitro. Moreover, quantitative proteomic approach identified 141 proteins differentially expressed only in SF/Con group. Bioinformatic analysis of these proteins revealed that oxidation-reduction process, RNA processing, fatty acid degradation, as well as melanin biosynthetic process were enriched with SF treatment. The proteins associated with melanin biosynthetic process, including microphthalmia-associated transcription factor (MITF) and tyrosinase, were down-regulated in SF group, which was confirmed by western blot. SIGNIFICANCE: SF inhibited melanin synthesis in B16 melanoma cells via down-regulation of MITF and tyrosinase expression, which provides a rationale for future utilization of SF.


Assuntos
Fibroínas/farmacologia , Melaninas/biossíntese , Melanoma Experimental/metabolismo , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Proteômica , Animais , Melanoma Experimental/patologia , Camundongos , Pironas/farmacologia , Reprodutibilidade dos Testes
4.
Int J Mol Sci ; 22(17)2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34502054

RESUMO

Equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman, EQ), one of the major intestinally derived metabolites of daidzein, the principal isoflavane found in soybeans and most soy foods, has recently attracted increased interest as a health-beneficial compound for estrogen-dependent diseases. However, based on its structure with two p-substituted phenols, this study aimed to examine whether EQ is a substrate for tyrosinase and whether it produces o-quinone metabolites that are highly cytotoxic to melanocyte. First, the tyrosinase-catalyzed oxidation of EQ was performed, which yielded three EQ-quinones. They were identified after being reduced to their corresponding catechols with NaBH4 or L-ascorbic acid. The binding of the EQ-quinones to N-acetyl-L-cysteine (NAC), glutathione (GSH), and bovine serum albumin via their cysteine residues was then examined. NAC and GSH afforded two mono-adducts and one di-adduct, which were identified by NMR and MS analysis. It was also found that EQ was oxidized to EQ-di-quinone in cells expressing human tyrosinase. Finally, it was confirmed that the EQ-oligomer, the EQ oxidation product, exerted potent pro-oxidant activity by oxidizing GSH to the oxidized GSSG and concomitantly producing H2O2. These results suggest that EQ-quinones could be cytotoxic to melanocytes due to their binding to cellular proteins.


Assuntos
Equol/metabolismo , Melanócitos/efeitos dos fármacos , Oxidantes/toxicidade , Quinonas/toxicidade , Cisteína/análogos & derivados , Cisteína/metabolismo , Glutationa/metabolismo , Células HEK293 , Humanos , Monofenol Mono-Oxigenase/metabolismo , Oxidantes/metabolismo , Ligação Proteica , Quinonas/metabolismo , Soroalbumina Bovina/metabolismo
5.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360871

RESUMO

The root of Pueraria lobata (Willd.) is a widely used herbal medicine worldwide, whereas the stem of the plant is discarded or used as feed for livestock. To reuse and exploit the stem of P. lobata as a resource, we investigated its potential as a skin-whitening agent. We found that the developed, enriched P. lobata stem (PLS) extract significantly inhibited melanin production in the 3-isobutyl-1-methylxanthine-induced B16/F10 cells at a concentration of 50 µg/mL. To further confirm the mechanism of the antimelanogenic effect of the enriched PLS extracts, we examined the mRNA expression of tyrosinase, which was suppressed by the extracts. To standardize and implement effective quality control of the enriched PLS extracts, its major chemical constituents were identified by high-performance liquid chromatography-photodiode array-electrospray ionization-mass spectrometry. In total, 12 constituents were identified. In silico analysis showed that the main constituents, puerarin and daidzin, had excellent binding affinities for human tyrosinase. Collectively, our results suggest that the PLS extracts could be used as anti-pigmentation agents.


Assuntos
Melaninas/biossíntese , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Caules de Planta/química , Pueraria/química , Preparações Clareadoras de Pele/farmacologia , Linhagem Celular Tumoral , Humanos , Isoflavonas/farmacologia , Melanoma Experimental , Monofenol Mono-Oxigenase/metabolismo
6.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361022

RESUMO

Gamma-aminobutyric acid (GABA) is considered the primary inhibitory neurotransmitter in the human cortex. However, whether GABA regulates melanogenesis has not been comprehensively elucidated. In this study, we reveal that GABA (20 mM) significantly inhibited α-melanocyte-stimulating hormone (α-MSH)-induced extracellular (from 354.9% ± 28.4% to 126.5% ± 16.0%) and intracellular melanin contents (from 236.7% ± 11.1% to 102.7% ± 23.1%) in B16F10 melanoma cells, without inducing cytotoxicity. In addition, α-MSH-induced hyperpigmentation in zebrafish larvae was inhibited from 246.3% ± 5.4% to 116.3% ± 3.1% at 40 mM GABA, displaying no apparent cardiotoxicity. We also clarify that the GABA-mediated antimelanogenic properties were related to the direct inhibition of microphthalmia-associated transcription factor (MITF) and tyrosinase expression by inhibiting cyclic adenosine monophosphate (cAMP) and cAMP response element-binding protein (CREB). Furthermore, under α-MSH stimulation, GABA-related antimelanogenic effects were mediated through the GABAA and GABAB receptors, with subsequent inhibition of Ca2+ accumulation. In B16F10 melanoma cells and zebrafish larvae, pretreatment with bicuculline, a GABAA receptor antagonist, and CGP 46381, a GABAB receptor antagonist, reversed the antimelanogenic effect of GABA following α-MSH treatment by upregulating Ca2+ accumulation. In conclusion, our results indicate that GABA inhibits α-MSH-induced melanogenesis. Hence, in addition to the health benefits of GABA in the central nervous system, it could ameliorate hyperpigmentation disorders.


Assuntos
Melaninas/biossíntese , Receptores de GABA-B/metabolismo , alfa-MSH/metabolismo , Ácido gama-Aminobutírico/metabolismo , Animais , Sinalização do Cálcio , Linhagem Celular Tumoral , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Humanos , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Receptores de GABA-A/metabolismo , Peixe-Zebra
7.
Molecules ; 26(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34443550

RESUMO

To confirm that the ß-phenyl-α,ß-unsaturated thiocarbonyl (PUSTC) scaffold, similar to the ß-phenyl-α,ß-unsaturated carbonyl (PUSC) scaffold, acts as a core inhibitory structure for tyrosinase, twelve (Z)-5-(substituted benzylidene)-4-thioxothiazolidin-2-one ((Z)-BTTZ) derivatives were designed and synthesized. Seven of the twelve derivatives showed stronger inhibitory activity than kojic acid against mushroom tyrosinase. Compound 2b (IC50 = 0.47 ± 0.97 µM) exerted a 141-fold higher inhibitory potency than kojic acid. Kinetic studies' results confirmed that compounds 2b and 2f are competitive tyrosinase inhibitors, which was supported by high binding affinities with the active site of tyrosinase by docking simulation. Docking results using a human tyrosinase homology model indicated that 2b and 2f might potently inhibit human tyrosinase. In vitro assays of 2b and 2f were conducted using B16F10 melanoma cells. Compounds 2b and 2f significantly and concentration-dependently inhibited intracellular melanin contents, and the anti-melanogenic effects of 2b at 10 µM and 2f at 25 µM were considerably greater than the inhibitory effect of kojic acid at 25 µM. Compounds 2b and 2f similarly inhibited cellular tyrosinase activity and melanin contents, indicating that the anti-melanogenic effects of both were due to tyrosinase inhibition. A strong binding affinity with the active site of tyrosinase and potent inhibitions of mushroom tyrosinase, cellular tyrosinase activity, and melanin generation in B16F10 cells indicates the PUSTC scaffold offers an attractive platform for the development of novel tyrosinase inhibitors.


Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Melaninas/biossíntese , Tiazóis/química , Tiazóis/farmacologia , Linhagem Celular Tumoral , Simulação por Computador , Inibidores Enzimáticos/metabolismo , Humanos , Cinética , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/química , Monofenol Mono-Oxigenase/metabolismo , Conformação Proteica , Relação Estrutura-Atividade , Tiazóis/metabolismo
8.
Int J Mol Sci ; 22(15)2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34360963

RESUMO

The insect immune response is initiated by the recognition of invading microorganisms. Peptidoglycan recognition proteins (PGRPs) function primarily as pattern recognition receptors by specifically binding to peptidoglycans expressed on microbial surfaces. We cloned a full-length cDNA for a PGRP from the Asian corn borer Ostrinia furnacalis (Guenée) and designated it as PGRP1. PGRP1 mRNA was mainly detected in the fat bodies and hemocytes. Its transcript levels increased significantly upon bacterial and fungal challenges. Purified recombinant PGRP1 exhibited binding activity to the gram-positive Micrococcus luteus, gram-negative Escherichia coli, entomopathogenic fungi Beauveria bassiana, and yeast Pichia pastoris. The binding further induced their agglutination. Additionally, PGRP1 preferred to bind to Lys-type peptidoglycans rather than DAP-type peptidoglycans. The addition of recombinant PGRP1 to O. furnacalis plasma resulted in a significant increase in phenoloxidase activity. The injection of recombinant PGRP1 into larvae led to a significantly increased expression of several antimicrobial peptide genes. Taken together, our results suggest that O. furnacalis PGRP1 potentially recognizes the invading microbes and is involved in the immune response in O. furnacalis.


Assuntos
Imunidade Inata , Proteínas de Insetos/metabolismo , Lepidópteros/genética , Peptidoglicano/metabolismo , Animais , Beauveria/patogenicidade , Corpo Adiposo/metabolismo , Hemócitos/metabolismo , Proteínas de Insetos/genética , Lepidópteros/imunologia , Lepidópteros/microbiologia , Micrococcus luteus/patogenicidade , Monofenol Mono-Oxigenase/metabolismo , Peptidoglicano/genética , Proteínas Citotóxicas Formadoras de Poros/genética , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Saccharomycetales/patogenicidade
9.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361043

RESUMO

Intravesicular pH plays a crucial role in melanosome maturation and function. Melanosomal pH changes during maturation from very acidic in the early stages to neutral in late stages. Neutral pH is critical for providing optimal conditions for the rate-limiting, pH-sensitive melanin-synthesizing enzyme tyrosinase (TYR). This dramatic change in pH is thought to result from the activity of several proteins that control melanosomal pH. Here, we computationally investigated the pH-dependent stability of several melanosomal membrane proteins and compared them to the pH dependence of the stability of TYR. We confirmed that the pH optimum of TYR is neutral, and we also found that proteins that are negative regulators of melanosomal pH are predicted to function optimally at neutral pH. In contrast, positive pH regulators were predicted to have an acidic pH optimum. We propose a competitive mechanism among positive and negative regulators that results in pH equilibrium. Our findings are consistent with previous work that demonstrated a correlation between the pH optima of stability and activity, and they are consistent with the expected activity of positive and negative regulators of melanosomal pH. Furthermore, our data suggest that disease-causing variants impact the pH dependence of melanosomal proteins; this is particularly prominent for the OCA2 protein. In conclusion, melanosomal pH appears to affect the activity of multiple melanosomal proteins.


Assuntos
Antígenos de Neoplasias/química , ATPases Transportadoras de Cobre/química , Melanossomas/metabolismo , Proteínas de Membrana Transportadoras/química , Simulação de Dinâmica Molecular , Monofenol Mono-Oxigenase/química , Prótons , Antígenos de Neoplasias/metabolismo , ATPases Transportadoras de Cobre/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Melanossomas/química , Proteínas de Membrana Transportadoras/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Estabilidade Proteica
10.
Fungal Biol ; 125(9): 667-678, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34420694

RESUMO

This study investigated the potential functions of Pleurotus florida (an edible mushroom) in the biodegradation of gas oil at concentrations of 0 (control), 2.5, 5, and 10% (V: V) for 30 days. The gas oil increased dry weight and protein concentration in all treatments (by an average of 19.5 and 108%, respectively). Moreover, the pH, surface tension (ST), and interfacial tension (IFT) were reduced by the mushroom supplementation. The lowest surface tension (31.9 mN m-1) and the highest biosurfactant production belonged to the 10% gas oil treatment (0.845 ± 0.03 mg mL-1). The results demonstrated that the adsorption isotherm agreed well with the Langmuir isotherm. The maximum Langmuir adsorption capacity was calculated at 0.743 mg g-1 wet biomass of P. florida. The fungal supplementation efficiently remedied the total petroleum hydrocarbons (TPHs) by an average of 55% after 30 days. Gas chromatography (GC) analysis revealed that P. florida effectively detoxified C13-C28 hydrocarbons, Pristane, and Phytane, implying its high mycoremediation function. The toxicity test showed that mycoremediation increased the germination by an average of 35.82% ± 8.89 after 30 days. Laccase activity increased significantly with increasing gas oil concentration in the treatments. The maximum laccase activity was obtained in the 10% gas oil treatment (142.25 ± 0.72 U L-1). The presence of pollutants was also associated with induction in the tyrosinase activity when compared to the control. These results underline the high mycoremediation capacity of P. florida through the involvement of biosurfactants, laccase, and tyrosinase.


Assuntos
Biodegradação Ambiental , Petróleo , Pleurotus , Poluentes Ambientais/metabolismo , Poluentes Ambientais/toxicidade , Lacase/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Petróleo/metabolismo , Petróleo/toxicidade , Pleurotus/efeitos dos fármacos , Pleurotus/enzimologia , Pleurotus/metabolismo
11.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360537

RESUMO

Human tyrosinase (Tyr) is a glycoenzyme that catalyzes the first and rate-limiting step in melanin production, and its gene (TYR) is mutated in many cases of oculocutaneous albinism type 1 (OCA1). The mechanisms by which individual mutations contribute to the diverse pigmentation phenotype in patients with OCA1 have only began to be examined and remain to be delineated. Here, we analyze the temperature-dependent kinetics of wild-type Tyr (WT) and two OCA1B mutant variants (R422Q and P406L) using Michaelis-Menten and Van't Hoff analyses. Recombinant truncated human Tyr proteins (residues 19-469) were produced in the whole insect Trichoplusia Ni larvae. Proteins were purified by a combination of affinity and size-exclusion chromatography. The temperature dependence of diphenol oxidase protein activities and kinetic parameters were measured by dopachrome absorption. Using the same experimental conditions, computational simulations were performed to assess the temperature-dependent association of L-DOPA and Tyr. Our results revealed, for the first time, that the association of L-DOPA with R422Q and P406L followed by dopachrome formation is a complex reaction supported by enthalpy and entropy forces. We show that the WT has a higher turnover number as compared with both R422Q and P406L. Elucidating the kinetics and thermodynamics of mutant variants of Tyr in OCA1B helps to understand the mechanisms by which they lower Tyr catalytic activity and to discover novel therapies for patients.


Assuntos
Albinismo Oculocutâneo/patologia , Monofenol Mono-Oxigenase/metabolismo , Mutação , Fenótipo , Temperatura , Albinismo Oculocutâneo/enzimologia , Albinismo Oculocutâneo/etiologia , Catálise , Humanos , Cinética , Monofenol Mono-Oxigenase/genética
12.
Arch Insect Biochem Physiol ; 108(1): e21764, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34272769

RESUMO

Melanization is mediated by the prophenoloxidase (proPO) activation cascade and plays an important role in the arthropods immune system. Previously, we found that the hemolymph of the p50 strain does not perform melanization after infection with Autographa californica multiple nucleopolyhedrovirus (AcMNPV). However, this mechanism is still unclear. In this study, the underlying mechanism of the inhibition of hemolymph melanization was investigated by analysing the AcMNPV-susceptible or -resistant silkworm strains after inoculation with AcMNPV. The results showed that the level of hemolymph melanization was higher in resistant strain C108 than in susceptible strain p50 at the late stage (72 to 120 h postinoculation). The PO activity decreased significantly at the late stage of infection (72 to 120 hpi), and the expression of BmPPO1 and BmPPO2 was downregulated in p50. However, the PO activity increased in the resistant strain C108, while the expression level of BmPPO1 and BmPPO2 displayed no significant changes. The expression of the BmPPAE gene was upregulated in two strains during viral infection. In addition, the hemolymph melanization can weaken the viral activity in vitro. Our results suggested that the silkworm hemolymph melanization response is related to defence against the AcMNPV infection.


Assuntos
Bombyx , Imunidade , Melaninas/metabolismo , Nucleopoliedrovírus/imunologia , Animais , Bombyx/imunologia , Bombyx/virologia , Hemolinfa/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Viroses/veterinária
13.
J Chem Ecol ; 47(7): 597-613, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34232439

RESUMO

Melanin is a heteropolymer formed by the polymerization of phenolic and indolic compounds. It occurs in organisms across all biological kingdoms and has a range different of functions, thus indicating its important evolutionary role. The presence of melanin offers several protective advantages, including against ultraviolet radiation, traumatic damage, oxidative stress, extreme temperatures, and pressure. For many species of fungi, melanin also participates directly in the process of virulence and pathogenicity. These organisms can synthesize melanin in two main ways: using a substrate of endogenous origin, involving 1,8-dihydroxynaphthalene (DHN); alternatively, in an exogenous manner with the addition of L-3, 4-dihydroxyphenylalanine (L-DOPA or levodopa). As melanin is an amorphous and complex substance, its study requires expensive and inaccessible technologies and analyses are often difficult to perform with conventional biochemical techniques. As such, details about its chemical structure are not yet fully understood, particularly for nematophagous fungi that remain poorly studied. Thus, this review presents an overview of the different types of melanin, with an emphasis on fungi, and discusses the role of melanin in the biology and ecology of nematophagous fungi.


Assuntos
Fungos/metabolismo , Melaninas/metabolismo , Fungos/patogenicidade , Lacase/metabolismo , Levodopa/química , Levodopa/metabolismo , Melaninas/química , Monofenol Mono-Oxigenase/metabolismo , Naftóis/química , Naftóis/metabolismo , Policetídeo Sintases/metabolismo
14.
Molecules ; 26(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208619

RESUMO

Skin pigment disorders are common cosmetic and medical problems. Many known compounds inhibit the key melanin-producing enzyme, tyrosinase, but their use is limited due to side effects. Natural-derived peptides also display tyrosinase inhibition. Abalone is a good source of peptides, and the abalone proteins have been used widely in pharmaceutical and cosmetic products, but not for melanin inhibition. This study aimed to predict putative tyrosinase inhibitory peptides (TIPs) from abalone, Haliotis diversicolor, using k-nearest neighbor (kNN) and random forest (RF) algorithms. The kNN and RF predictors were trained and tested against 133 peptides with known anti-tyrosinase properties with 97% and 99% accuracy. The kNN predictor suggested 1075 putative TIPs and six TIPs from the RF predictor. Two helical peptides were predicted by both methods and showed possible interaction with the predicted structure of mushroom tyrosinase, similar to those of the known TIPs. These two peptides had arginine and aromatic amino acids, which were common to the known TIPs, suggesting non-competitive inhibition on the tyrosinase. Therefore, the first version of the TIP predictors could suggest a reasonable number of the TIP candidates for further experiments. More experimental data will be important for improving the performance of these predictors, and they can be extended to discover more TIPs from other organisms. The confirmation of TIPs in abalone will be a new commercial opportunity for abalone farmers and industry.


Assuntos
Gastrópodes/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Algoritmos , Animais , Análise por Conglomerados , Biologia Computacional/métodos , Gastrópodes/química , Aprendizado de Máquina , Monofenol Mono-Oxigenase/farmacologia , Peptídeos/farmacologia
15.
Molecules ; 26(12)2021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34199192

RESUMO

The beneficial effects of coffee on human diseases are well documented, but the molecular mechanisms of its bioactive compounds on cancer are not completely elucidated. This is likely due to the large heterogeneity of coffee preparations and different coffee-based beverages, but also to the choice of experimental models where proliferation, differentiation and immune responses are differently affected. The aim of the present study was to investigate the effects of one of the most interesting bioactive compounds in coffee, i.e., caffeine, using a cellular model of melanoma at a defined differentiation level. A preliminary in silico analysis carried out on public gene-expression databases identified genes potentially involved in caffeine's effects and suggested some specific molecular targets, including tyrosinase. Proliferation was investigated in vitro on human melanoma initiating cells (MICs) and cytokine expression was measured in conditioned media. Tyrosinase was revealed as a key player in caffeine's mechanisms of action, suggesting a crucial role in immunomodulation through the reduction in IL-1ß, IP-10, MIP-1α, MIP-1ß and RANTES secretion onto MICs conditioned media. The potent antiproliferative effects of caffeine on MICs are likely to occur by promoting melanin production and reducing inflammatory signals' secretion. These data suggest tyrosinase as a key player mediating the effects of caffeine on melanoma.


Assuntos
Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Simulação por Computador/estatística & dados numéricos , Melaninas/metabolismo , Melanoma/tratamento farmacológico , Monofenol Mono-Oxigenase/metabolismo , Diferenciação Celular , Linhagem Celular Tumoral , Biologia Computacional/métodos , Bases de Dados Genéticas , Regulação da Expressão Gênica , Humanos , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia
16.
Molecules ; 26(14)2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34299485

RESUMO

Oxyresveratrol has recently attracted much research attention due to its simple chemical structure and diverse therapeutic potentials. Previous reviews describe the chemistry and biological activities of this phytoalexin, but additional coverage and greater accessibility are still needed. The current review provides a more comprehensive summary, covering research from 1955 to the present year. Oxyresveratrol occurs in both gymnosperms and angiosperms. However, it has never been reported in plants in the subclass Sympetalae, and this point might be of both chemotaxonomic and biosynthetic importance. Oxyresveratrol can be easily obtained from plant materials by conventional methods, and several systems for both qualitative and quantitative analysis of oxyresveratrol contents in plant materials and plant products are available. Oxyresveratrol possesses diverse biological and pharmacological activities such as the inhibition of tyrosinase and melanogenesis, antioxidant and anti-inflammatory activities, and protective effects against neurological disorders and digestive ailments. However, the unfavorable pharmacokinetic properties of oxyresveratrol, including low water solubility and poor oral availability and stability, have posed challenges to its development as a useful therapeutic agent. Recently, several delivery systems have emerged, with promising outcomes that may improve chances for the clinical study of oxyresveratrol.


Assuntos
Extratos Vegetais/farmacologia , Extratos Vegetais/farmacocinética , Estilbenos/farmacologia , Estilbenos/farmacocinética , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Humanos , Monofenol Mono-Oxigenase/metabolismo
17.
Chem Biodivers ; 18(8): e2100299, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34086421

RESUMO

The article reports the chemical composition, antioxidant, six key enzymes inhibitory and antimicrobial activities of two solvent extracts (water and methanol) of leaves and stem bark of Uapaca togoensis. For chemical composition, methanol extract of stem bark exhibited significant higher total phenolic (129.86 mg GAE/g) and flavanol (10.44 mg CE/g) contents. Methanol extract of leaves and water extract of stem bark showed high flavonoids (20.94 mg RE/g) and phenolic acid (90.40 mg CAE/g) content, respectively. In addition, HPLC-ESI-TOF-MS analysis revealed that U. togoensis was rich in procyanidins. The methanol and water extracts of stem bark had overall superior antioxidant activity; however, only methanol extract of stem bark showed higher inhibition of cholinesterase (AChE: 2.57 mg GALAE/g; BChE: 4.69 mg GALAE/g), tyrosinase (69.53 mg KAE/g) and elastase (2.73 mmol CE/g). Potent metal chelating ability was showed by water extract of leaves (18.94 mg EDTAE/g), higher inhibition of amylase was detected for water extracts of leaves (0.94 mmol ACAE/g) and stem bark (0.92 mmol ACAE/g). The tested extracts have shown wide-spectrum antibacterial properties and these effects have shown to be more effective against Aspergillus ochraceus, Penicillium funiculosum, Trichoderma viride, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The results revealed that the antioxidant, enzyme inhibitory and antimicrobial activities depended on the extraction solvents and the parts of plant. Bioinformatics analysis on the 17 major compounds showed modulation of pathway associated with cancer. In brief, U. togoensis might be valuable as potential source of natural agents for therapeutic application.


Assuntos
Biflavonoides/química , Catequina/química , Biologia Computacional/métodos , Inibidores Enzimáticos/química , Magnoliopsida/química , Extratos Vegetais/química , Proantocianidinas/química , Amilases/antagonistas & inibidores , Amilases/metabolismo , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antioxidantes/química , Biflavonoides/isolamento & purificação , Biflavonoides/metabolismo , Biflavonoides/farmacologia , Catequina/isolamento & purificação , Catequina/metabolismo , Catequina/farmacologia , Cromatografia Líquida de Alta Pressão , Análise por Conglomerados , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Fungos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Magnoliopsida/metabolismo , Testes de Sensibilidade Microbiana , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Casca de Planta/química , Casca de Planta/metabolismo , Folhas de Planta/química , Folhas de Planta/metabolismo , Proantocianidinas/isolamento & purificação , Proantocianidinas/metabolismo , Proantocianidinas/farmacologia , Espectrometria de Massas por Ionização por Electrospray
18.
Chem Biodivers ; 18(8): e2100207, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34096170

RESUMO

Gundelia species are known as "Kenger-kereng dikeni" in Anatolia, and their aerial parts are consumed as food. Also, roots and seeds (disseminules) of the Gundelia species are used to prepare gum and coffee. The chemical contents of ethanol and hexane extracts of disseminules of 17 Gundelia species, 13 of them are endemic, were studied using LC/MS/MS and GC/MS. Additionally, their antioxidant potential and enzyme inhibitory capacity against acetyl- and butyryl-cholinesterase, urease, and tyrosinase were determined. The unsaturated fatty acid ratios of Gundelia species were higher than their saturated fatty acid ratio. The highest sum of oleic and linoleic acid was detected in G. tournefortii var. tenuisecta (70.42 %). ß-Sitosterol, α-amyrin, 3-acetyllupeol were identified in 17 Gundelia species by GC/MS, while chlorogenic acid and luteolin by LC/MS/MS as major compounds. The ethanol and hexane extracts of G. siirtica, G. rosea, and G. mesopotamica indicated good cholinesterase inhibitory activity. Among all species, ethanol extract of G. colemerikensis exhibited the best activity in ABTS (IC50 : 32.30±0.98 µg/mL), DPPH (IC50 : 59.91±0.89 µg/mL), and CUPRAC (A0.5 : 57.41±1.03 µg/mL) assays. Ethanol extract of G. colemerikensis also displayed the highest inhibitory activity against butyrylcholinesterase (51.14±0.25 % at 200 µg/mL), urease (51.71±1.75 % at 200 µg/mL), and tyrosinase (39.50±0.85 % at 200 µg/mL) enzymes. According to the chemometric analysis of fatty acids, four groups were observed. Therefore, it is suggested that G. colemerikensis can be used in the pharmaceutical, food, and cosmetic industries due to its antioxidant and enzyme inhibition properties.


Assuntos
Asteraceae/química , Inibidores Enzimáticos/química , Compostos Fitoquímicos/química , Extratos Vegetais/química , Antioxidantes/química , Asteraceae/metabolismo , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Ácidos Graxos/química , Ácidos Graxos/isolamento & purificação , Frutas/química , Frutas/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/metabolismo , Análise de Componente Principal , Sementes/química , Sementes/metabolismo , Espectrometria de Massas em Tandem , Urease/antagonistas & inibidores , Urease/metabolismo
19.
Chem Biodivers ; 18(8): e2100316, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34114723

RESUMO

The genus Rhanterium (Asteraceae) is a widely distributed medicinal plant throughout western North Africa and some Rhanterium species are used in folk medicine. The aim of research was to investigate methanolic extracts from different parts (flowers, leaves, and stems) of Tunisian Rhanterium suaveolens as potential sources of bioactive products useful for healthy purposes. In particular, were analyzed the phenolic composition of these extracts and their antioxidant, anti-inflammatory, and anti-tyrosinase properties. The phytochemical analyses were performed using standard colorimetric procedures, HPLC-DAD and HPLC-DAD-ESI-MS. Then, several in vitro cell-free assays have been used to estimate the antioxidant/free radical scavenging capability of the extracts. Moreover, in vitro, and in vivo anti-melanogenesis activities of these extracts were tested, respectively, with the tyrosinase inhibition assay and the Zebrafish embryo model. Finally, the anti-inflammatory potential of these extracts in an in vitro model of acute intestinal inflammation in differentiated Caco-2 cells was evaluated. The R. suaveolens extracts under study appeared particularly rich in flavonols and hydroxycinnamic acids and all extracts appeared endowed with good antioxidant/free radical scavenging properties, being the flower extracts slightly more active than the others. Moreover, R. suaveolens flowers extract was able to inhibit in vitro tyrosinase activity and exhibited bleaching effects on the pigmentation of zebrafish embryos. Furthermore, all extracts showed good anti-inflammatory activity in intestinal epithelial cells as demonstrated by the inhibition of TNF-α-induced gene expression of IL-6 and IL-8. R. suaveolens aerial parts may be considered as a potential source of whitening agents, as well as of agents for the treatment of disorders related to oxidative stress and inflammation.


Assuntos
Anti-Inflamatórios/química , Asteraceae/química , Inibidores Enzimáticos/química , Monofenol Mono-Oxigenase/antagonistas & inibidores , Extratos Vegetais/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Asteraceae/metabolismo , Células CACO-2 , Diferenciação Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ácidos Cumáricos/química , Ácidos Cumáricos/isolamento & purificação , Ácidos Cumáricos/metabolismo , Ácidos Cumáricos/farmacologia , Embrião não Mamífero/citologia , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Flavonóis/química , Flavonóis/isolamento & purificação , Flavonóis/metabolismo , Flavonóis/farmacologia , Humanos , Melaninas/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Plantas Medicinais/química , Plantas Medicinais/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Tunísia , Peixe-Zebra/metabolismo
20.
Anal Chim Acta ; 1169: 338605, 2021 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-34088368

RESUMO

Melanoma, the skin cancer with the highest mortality rate, can be diagnosed at the early stage by detecting unique biomarkers. Over-expressed tyrosinase has been confirmed by dozens of clinical studies as an independent factor to evaluate the malignancy of melanoma. Using Enteromorpha Prolifera as the raw material, herein we develop a novel fluorescent probe, ECDY, which can sensitively detect the tyrosinase activity in different types of cells. More importantly, melanoma cells can be specifically distinguished through cell lysate measurements as well as the whole-cell imaging technique. Mechanically, the tyrosine groups on the surface of ECDY can be specifically recognized by tyrosinase and further converted into dopaquinone, which consequently causes the intramolecular fluorescence quenching of the probe through photoinduced electron transfer (PET). Tyrosinase can be detected within 20 min in the solution, and the detection limit is as low as 0.067 U mL-1. For the in vitro demonstration, we evaluate the fluorescence decay of ECDY in response to the intracellular tyrosinase activity within the lysate of various cell lines, including non-cancerous, non-melanoma cancerous, and mouse melanoma ones. The experimental results verify that ECDY can accurately measure the apparent tyrosinase activity in different cell lines and detect melanoma cell lysate specifically. The confocal fluorescence imaging experiments further demonstrate that ECDY can distinguish melanoma cells from others significantly. We believe that ECDY provides a new strategy for the efficient detection of tyrosinase and melanoma cells, and is expected to apply as a clinical diagnosis platform.


Assuntos
Melanoma , Monofenol Mono-Oxigenase , Animais , Transporte de Elétrons , Corantes Fluorescentes , Camundongos , Monofenol Mono-Oxigenase/metabolismo , Imagem Óptica
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