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1.
Phytochemistry ; 213: 113751, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37307887

RESUMO

Boswellia dalzielii is a resin-producing tree endemic to West and Central Africa, used by local populations for various medicinal purposes. In this study, B. dalzielii gum resin was analyzed by GC-MS and UHPLC-MS to identify and quantify volatile and non-volatile compounds. Its main volatile constituents were α-pinene (54.9%), followed by α-thujene (4.4%) and α-phellandren-8-ol (4.0%). Pentacyclic triterpenoids such as ß-boswellic acids and their derivatives were quantified by UHPLC-MS and their content was shown to reach around 22% of the gum resin. Since some of the volatile and non-volatile compounds identified in this work are known to possess biological effects, the bioactivities of B. dalzielii ethanolic extract, essential oil, as well as fractions of the oil and extract were evaluated. Some of these samples exhibited interesting anti-inflammatory properties, and their antioxidant, anti-ageing and skin-bleaching activities were also tested.


Assuntos
Boswellia , Compostos Fitoquímicos , Resinas Vegetais , Envelhecimento/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Boswellia/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Resinas Vegetais/química , Preparações Clareadoras de Pele/química , Preparações Clareadoras de Pele/farmacologia , Triterpenos/química , Triterpenos/farmacologia
2.
Int J Mol Sci ; 24(7)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37047130

RESUMO

Anti-pigmentation peptides have been developed as alternative skin-lightening agents to replace conventional chemicals that have adverse effects on the skin. However, the maximum size of these peptides is often limited by their low skin and cell penetration. To address this issue, we used our intra-dermal delivery technology (IDDT) platform to identify peptides with hypo-pigmenting and high cell-penetrating activity. Using our cell-penetrating peptides (CPPs) from the IDDT platform, we identified RMNE1 and its derivative RMNE3, "DualPep-Shine", which showed levels of α-Melanocyte stimulating hormone (α-MSH)-induced melanin inhibition comparable to the conventional tyrosinase inhibitor, Kojic acid. In addition, DualPep-Shine was delivered into the nucleus and regulated the gene expression levels of melanogenic enzymes by inhibiting the promoter activity of microphthalmia-associated transcription factor-M (MITF-M). Using a 3D human skin model, we found that DualPep-Shine penetrated the lower region of the epidermis and reduced the melanin content in a dose-dependent manner. Furthermore, DualPep-Shine showed high safety with little immunogenicity, indicating its potential as a novel cosmeceutical ingredient and anti-pigmentation therapeutic agent.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Peptídeos Penetradores de Células , Melaninas , Melanócitos , Fator de Transcrição Associado à Microftalmia , Proteínas do Tecido Nervoso , Preparações Clareadoras de Pele , Pigmentação da Pele , Transcrição Gênica , Melaninas/antagonistas & inibidores , Pigmentação da Pele/efeitos dos fármacos , Fator de Transcrição Associado à Microftalmia/genética , Transcrição Gênica/efeitos dos fármacos , alfa-MSH/antagonistas & inibidores , alfa-MSH/metabolismo , Humanos , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/farmacologia , Preparações Clareadoras de Pele/química , Preparações Clareadoras de Pele/farmacologia , Melanoma Experimental , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/farmacologia , Fatores de Transcrição Hélice-Alça-Hélice Básicos/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Melanócitos/efeitos dos fármacos , Melanócitos/metabolismo , Epiderme/efeitos dos fármacos , Epiderme/metabolismo
3.
Molecules ; 26(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33669031

RESUMO

Response surface methodology was employed to optimize the ultrasound-assisted extraction (UAE) conditions for simultaneous optimization of dependent variables, including DPPH radical scavenging activity (RSA), tyrosinase activity inhibition (TAI), and collagenase activity inhibition (CAI) of peanut shell extracts. The effects of the main variables including extraction time (5.0~55.0 min, X1), extraction temperature (26.0~94.0 °C, X2), and ethanol concentration (0.0%~99.5%, X3) were optimized. Based on experimental values from each condition, quadratic regression models were derived for the prediction of optimum conditions. The coefficient of determination (R2) of the independent variable was in the range of 0.89~0.96, which demonstrates that the regression model is suitable for the prediction. In predicting optimal UAE conditions based on the superimposing method, extraction time of 31.2 min, extraction temperature of 36.6 °C, and ethanol concentration of 93.2% were identified. Under these conditions, RSA of 74.9%, TAI of 50.6%, and CAI of 86.8% were predicted, showing good agreement with the experimental values. A reverse transcription polymerase chain reaction showed that peanut shell extract decreased mRNA levels of tyrosinase-related protein-1 and matrix metalloproteinase-3 genes in B16-F0 cell. Therefore, we identified the skin-whitening and anti-wrinkle effects of peanut shell extracts at protein as well as gene expression levels, and the results show that peanut shell is an effective cosmetic material for skin-whitening and anti-wrinkle effects. Based on this study, peanut shell, which was considered a byproduct, can be used for the development of healthy foods, medicines, and cosmetics.


Assuntos
Antioxidantes/farmacologia , Arachis/química , Extratos Vegetais/farmacologia , Preparações Clareadoras de Pele/farmacologia , Ondas Ultrassônicas , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , Oxirredutases/antagonistas & inibidores , Oxirredutases/genética , Oxirredutases/metabolismo , Picratos/antagonistas & inibidores , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Preparações Clareadoras de Pele/química , Preparações Clareadoras de Pele/isolamento & purificação , Células Tumorais Cultivadas
4.
Lipids ; 55(6): 649-659, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33128473

RESUMO

In the present study, we demonstrated that borage (Borago officinalis L.) seed oil subjected to immobilized lipase pretreatment are enriched with linoleic acid (LNA, 18:2n-6), γ-linolenic acid (GLA, 18:3n-6), and oleic acid (OLA, 18:1n-9). We further showed that lipase-treated borage oil (LT-BOL) regulates the activity and degradation of tyrosinase, an important enzyme implicated in the synthesis of melanin in murine melanocytes, B16F10. LT-BOL and its free fatty acid components reduced the levels of melanin and tyrosinase in melanocytes with GLA exerting similar or stronger effects compared with LNA and OLA. The brightening efficacy of LT-BOL on melanin metabolism in humans was tested by an 8-week, double-blind, randomized clinical trial, which enrolled 21 Korean female adults (mean age 48.57 ± 3.28). Visual evaluation showed that cream containing 1% LT-BOL significantly decreased (p < 0.05) melasma on the treated skin area after 6 and 8 weeks. The analysis of the skin brightness using Chromameter CR-400 confirmed that the brightness of the treated area was significantly increased (p < 0.01) after 4, 6, and 8 weeks. Together, our results suggest that LT-BOL may be suitable as a natural skin whitening cosmeceutical product.


Assuntos
Lipase/química , Melanócitos/efeitos dos fármacos , Óleos de Plantas/química , Óleos de Plantas/farmacologia , Preparações Clareadoras de Pele/farmacologia , Ácido gama-Linolênico/química , Ácido gama-Linolênico/farmacologia , Camellia/química , Método Duplo-Cego , Enzimas Imobilizadas/química , Ácidos Graxos não Esterificados/química , Ácidos Graxos não Esterificados/farmacologia , Feminino , Humanos , Melaninas/análise , Melaninas/metabolismo , Melanócitos/fisiologia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Pessoa de Meia-Idade , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Preparações Clareadoras de Pele/química
5.
J Med Chem ; 63(22): 13428-13443, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-32787103

RESUMO

Human tyrosinase (hsTYR) is the key enzyme ensuring the conversion of l-tyrosine to dopaquinone, thereby initiating melanin synthesis, i.e., melanogenesis. Although the protein has long been familiar, knowledge about its three-dimensional structure and efficient overexpression protocols emerged only recently. Consequently, for decades medicinal chemistry studies aiming at developing skin depigmenting agents relied almost exclusively on biological assays performed using mushroom tyrosinase (abTYR), producing a plethoric literature, often of little useful purpose. Indeed, several recent reports have pointed out spectacular differences in terms of interaction patterns and inhibition values between hsTYR and abTYR, including for widely used standard tyrosinase inhibitors. In this review, we summarize the last developments regarding the potential role of hsTYR in human pathologies, the advances in recombinant expression systems and structural data retrieving, and the pioneer generation of true hsTYR inhibitors. Finally, we present suggestions for the design of future inhibitors of this highly attractive target in pharmacology and dermocosmetics.


Assuntos
Agaricales , Sistemas de Liberação de Medicamentos/tendências , Inibidores Enzimáticos/administração & dosagem , Melaninas/antagonistas & inibidores , Monofenol Mono-Oxigenase/antagonistas & inibidores , Pigmentação/efeitos dos fármacos , Sequência de Aminoácidos , Fatores Biológicos/administração & dosagem , Fatores Biológicos/química , Fatores Biológicos/isolamento & purificação , Sistemas de Liberação de Medicamentos/métodos , Desenho de Fármacos , Inibidores Enzimáticos/química , Humanos , Melaninas/química , Melaninas/metabolismo , Melanócitos/efeitos dos fármacos , Melanócitos/enzimologia , Melanócitos/patologia , Melanoma/tratamento farmacológico , Melanoma/enzimologia , Melanoma/patologia , Monofenol Mono-Oxigenase/metabolismo , Pigmentação/fisiologia , Estrutura Secundária de Proteína , Preparações Clareadoras de Pele/administração & dosagem , Preparações Clareadoras de Pele/química
6.
Recent Pat Drug Deliv Formul ; 14(3): 223-232, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32479252

RESUMO

BACKGROUND: Many topical agents are available in the market, which interfere with the pigmentation process at different levels. They are often known to cause side effects ranging from irritation to tumor over chronic use. OBJECTIVE: The present study was designed to develop and characterize an anti blemish cream containing herbal oils. METHODS: A herbal cream was formulated using dill, nagarmotha and black cumin oil and subjected to evaluation of its anti blemish potential against stress augmented UV-B rays-induced hyperpigmentation. Topical oil in water type of creams containing 2%, 4% and 6% of each oil was formulated using herbal oils. The formulated cream was characterized for solubility, pH, particle size, grittiness, viscosity, stability, phase separation, shelf life and spreadability, and found to be stable. Acute dermal toxicity was carried out individually for dill, nagarmotha and black cumin oil according to the OECD guidelines 402. Hyperpigmentation was induced in all the experimental animals by stress-augmented UV-B irradiation method. The animals were treated for 30 days (twice daily) with standard and test formulations by topical administration, whereas the disease group was left untreated. The skin of the animals was subjected to photographical study as well as grading for pigmentation and irritation before and after treatment. After the treatment period, the serum antioxidant levels were estimated and histopathology, histochemical studies of skin were performed. RESULTS: The animals treated with test formulations containing 2%, 4%, and 6% of herbal oil showed significant improvement in pigmentation compared to disease control as it is evident in photographic biochemical, histopathological and histochemical studies. CONCLUSION: Thus, it was concluded that the developed anti-blemish cream containing herbal oils possesses significant anti-blemish potential. This study necessitates further evaluations in human subjects as it could have a high positive therapeutic value in the treatment of hyperpigmentation.


Assuntos
Hiperpigmentação/tratamento farmacológico , Óleos de Plantas/administração & dosagem , Preparações Clareadoras de Pele/administração & dosagem , Administração Cutânea , Anethum graveolens , Animais , Cyperus , Modelos Animais de Doenças , Composição de Medicamentos , Feminino , Hiperpigmentação/etiologia , Hiperpigmentação/patologia , Nigella sativa , Óleos de Plantas/química , Ratos Wistar , Creme para a Pele , Preparações Clareadoras de Pele/química , Pigmentação da Pele/efeitos da radiação , Estresse Psicológico/complicações , Raios Ultravioleta
7.
Mar Drugs ; 18(6)2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-32575468

RESUMO

Cosmetics are widely used by people around the world to protect the skin from external stimuli. Consumer preference towards natural cosmetic products has increased as the synthetic cosmetic products caused adverse side effects and resulted in low absorption rate due to the chemicals' larger molecular size. The cosmetic industry uses the term "cosmeceutical", referring to a cosmetic product that is claimed to have medicinal or drug-like benefits. Marine algae have gained tremendous attention in cosmeceuticals. They are one of the richest marine resources considered safe and possessed negligible cytotoxicity effects on humans. Marine algae are rich in bioactive substances that have shown to exhibit strong benefits to the skin, particularly in overcoming rashes, pigmentation, aging, and cancer. The current review provides a detailed survey of the literature on cosmeceutical potentials and applications of algae as skin whitening, anti-aging, anticancer, antioxidant, anti-inflammation, and antimicrobial agents. The biological functions of algae and the underlying mechanisms of all these activities are included in this review. In addition, the challenges of using algae in cosmeceutical applications, such as the effectiveness of different extraction methods and processing, quality assurance, and regulations concerning extracts of algae in this sector were also discussed.


Assuntos
Produtos Biológicos/farmacologia , Cosmecêuticos/farmacologia , Alga Marinha/química , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/uso terapêutico , Cosmecêuticos/química , Cosmecêuticos/isolamento & purificação , Cosmecêuticos/uso terapêutico , Exantema/tratamento farmacológico , Humanos , Estrutura Molecular , Neoplasias/tratamento farmacológico , Alga Marinha/metabolismo , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Preparações Clareadoras de Pele/química , Preparações Clareadoras de Pele/isolamento & purificação , Preparações Clareadoras de Pele/farmacologia , Preparações Clareadoras de Pele/uso terapêutico , Pigmentação da Pele/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos
8.
J Agric Food Chem ; 67(46): 12741-12751, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31659899

RESUMO

Tyrosinase inhibitors are important in cosmetic, medical, and food industries due to their regulation of melanin production. A tyrosinase inhibitor was purified from Camellia pollen using high-speed countercurrent chromatography and preparative high-performance liquid chromatography and was identified as caffeine by NMR and mass spectrometry. It showed strong mushroom tyrosinase inhibitory activity with an IC50 of 18.5 ± 2.31 µg/mL in a noncompetitive model. The caffeine did not interact with copper ions in the active center of the enzyme but could quench fluorescence intensity and change the secondary conformation of this tyrosinase. A molecular dynamics simulation showed that caffeine bound this tyrosinase via Lys379, Lys 376, Asp357, Glu356, Thr308, Gln307, Asp312, and Trp358, thus changing the binding sites of l-tyrosine and the loop conformation adjacent to the active center. In vitro cell model analysis revealed that caffeine exhibited significant inhibitory effects on both intracellular tyrosinase activity and melanin production of B16-F10 melanoma cells in a concentration-dependent manner. These comprehensive results suggest that caffeine is a strong tyrosinase inhibitor that has the potential to be developed as skin-whitening agents in the cosmetics and pharmaceutical industries or as antibrowning agents in the food industry.


Assuntos
Cafeína/química , Camellia/química , Inibidores Enzimáticos/química , Monofenol Mono-Oxigenase/antagonistas & inibidores , Extratos Vegetais/química , Pólen/química , Animais , Cafeína/isolamento & purificação , Linhagem Celular , Cobre , Melaninas/biossíntese , Camundongos , Simulação de Dinâmica Molecular , Preparações Clareadoras de Pele/química
9.
Carbohydr Polym ; 225: 115211, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521267

RESUMO

Fucoidan from Laminaria japonica is a kind of sulfate polysaccharide with high molecular weight (MW) and broad bioactivities. This study was performed to investigate the relationship between MW and whitening activity of fucoidan and to exploit a novel functional ingredient for whitening cosmetics. High sulfate content fucoidan was enzymic degraded by Flavobacterium RC2-3 produced fucoidanase. Two hours were enough for the enzyme degradation to achieve degraded fucoidan with favorable tyrosinase inhibitory ability. The whitening activity of different MW fucoidan fractions were evaluated by their tyrosinase inhibitory ability, antioxidant activity and cellular melanogenesis inhibitory ability. Results showed that in the MW range above 5 kDa, the smaller MW of fucoidan were related to the better whitening activity. The fucoidan fraction with the MW between 5-10 kDa, presented the best tyrosinase inhibitory activity (62.0%), antioxidant activity (48.3%) and excellent anti-melanogenesis ability in B16 cells, which could be applied as the whitening factor in cosmetics development.


Assuntos
Clareadores , Laminaria/metabolismo , Polissacarídeos , Preparações Clareadoras de Pele , Animais , Antioxidantes , Clareadores/química , Clareadores/farmacologia , Linhagem Celular Tumoral , Peso Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Polissacarídeos/química , Polissacarídeos/farmacologia , Preparações Clareadoras de Pele/química , Preparações Clareadoras de Pele/farmacologia , Sulfatos/metabolismo
10.
J Microencapsul ; 36(2): 130-139, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30982372

RESUMO

Phenylethyl resorcinol (PR) has been known to allow the whitening effect by inhibiting formation of tyrosinase. PR has solubility of 4.05 ± 0.02 mg/g for water and log P of 3.017, proposed an amphiphilic substance. Hybrid PLGA microspheres with oil (HPMSs) have been used to improve encapsulation efficiency (EE) of hydrophilic molecules and control the release of them. The solubility (618.3 ± 22.29 mg/g) of PR was the highest in CapryolTM 90. The formulations (F6 and F`6) were selected after evaluation with EE and the released % (w/w) at 8 h. HPMSs showed 40% (w/w) increase of EE compared to that in CPMSs. Retention study on rat skin at 12 h resulted in that PR of HPMSs was remained more than that of CPMSs in dermal layer forming the melanin. HPMSs showed 1.4-fold increase of tyrosinase inhibition significantly in melanoma cells than that of the PR solution at 24 h.


Assuntos
Compostos Benzidrílicos/administração & dosagem , Portadores de Fármacos/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Resorcinóis/administração & dosagem , Preparações Clareadoras de Pele/administração & dosagem , Animais , Compostos Benzidrílicos/química , Compostos Benzidrílicos/farmacocinética , Linhagem Celular , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Óleos/química , Ratos , Resorcinóis/química , Resorcinóis/farmacocinética , Pele/metabolismo , Absorção Cutânea , Preparações Clareadoras de Pele/química , Preparações Clareadoras de Pele/farmacocinética , Solubilidade
11.
Int J Mol Sci ; 19(12)2018 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-30545008

RESUMO

The rhizoma of Ligusticum sinense, a Chinese medicinal plant, has long been used as a cosmetic for the whitening and hydrating of the skin in ancient China. In order to investigate the antimelanogenic components of the rhizoma of L. sinense, we performed an antimelanogenesis assay-guided purification using semi-preparative HPLC accompanied with spectroscopic analysis to determine the active components. Based on the bioassay-guided method, 24 compounds were isolated and identified from the ethyl acetate layer of methanolic extracts of L. sinense, and among these, 5-[3-(4-hydroxy-3-methoxyphenyl)allyl]ferulic acid (1) and cis-4-pentylcyclohex-3-ene-1,2-diol (2) were new compounds. All the pure isolates were subjected to antimelanogenesis assay using murine melanoma B16-F10 cells. Compound 1 and (3S,3aR)-neocnidilide (8) exhibited antimelanogenesis activities with IC50 values of 78.9 and 31.1 µM, respectively, without obvious cytotoxicity. Further investigation showed that compound 8 demonstrated significant anti-pigmentation activity on zebrafish embryos (10‒20 µM) compared to arbutin (20 µM), and without any cytotoxicity against normal human epidermal keratinocytes. These findings suggest that (3S,3aR)-neocnidilide (8) is a potent antimelanogenic and non-cytotoxic natural compound and may be developed potentially as a skin-whitening agent for cosmetic uses.


Assuntos
Ligusticum/química , Preparações Clareadoras de Pele/química , Animais , Arbutina , Humanos , Queratinócitos/efeitos dos fármacos , Melanoma Experimental , Camundongos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Rizoma/química , Preparações Clareadoras de Pele/efeitos adversos , Preparações Clareadoras de Pele/farmacologia , Peixe-Zebra
12.
Bioorg Med Chem ; 26(21): 5672-5681, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30366788

RESUMO

Pigmentation disorders are attributed to excessive melanin which can be produced by tyrosinase. Therefore, tyrosinase is supposed to be a vital target for the treatment of disorders associated with overpigmentation. Based on our previous findings that an (E)-ß-phenyl-α,ß-unsaturated carbonyl scaffold can play a key role in the inhibition of tyrosinase activity, and the fact that cinnamic acid is a safe natural substance with a scaffolded structure, it was speculated that appropriate cinnamic acid derivatives may exhibit potent tyrosinase inhibitory activity. Thus, ten cinnamamides were designed, and synthesized by using a Horner-Emmons olefination as the key step. Cinnamamides 4 (93.72% inhibition), 9 (78.97% inhibition), and 10 (59.09% inhibition) with either a 2,4-dihydroxyphenyl, or 4-hydroxy-3-methoxyphenyl substituent showed much higher mushroom tyrosinase inhibition at 25 µM than kojic acid (18.81% inhibition), used as a positive control. Especially, the two cinnamamides 4 and 9 having a 2,4-dihydroxyphenyl group showed the strongest inhibition. Docking simulation with tyrosinase revealed that these three cinnamamides, 4, 9, and 10, bind to the active site of tyrosinase more strongly than kojic acid. Cell-based experiments carried out using B16F10 murine skin melanoma cells demonstrated that all three cinnamamides effectively inhibited cellular tyrosinase activity and melanin production in the cells without cytotoxicity. There was a close correlation between cellular tyrosinase activity and melanin content, indicating that the inhibitory effect of the three cinnamamides on melanin production is mainly attributed to their capability for cellular tyrosinase inhibition. These results imply that cinnamamides having the (E)-ß-phenyl-α,ß-unsaturated carbonyl scaffolds are promising candidates for skin-lighting agents.


Assuntos
Amidas/farmacologia , Cinamatos/farmacologia , Inibidores Enzimáticos/farmacologia , Melaninas/antagonistas & inibidores , Preparações Clareadoras de Pele/farmacologia , Agaricales/enzimologia , Amidas/síntese química , Amidas/química , Amidas/toxicidade , Animais , Linhagem Celular Tumoral , Cinamatos/síntese química , Cinamatos/química , Cinamatos/toxicidade , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/toxicidade , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/toxicidade , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/química , Pironas/química , Preparações Clareadoras de Pele/síntese química , Preparações Clareadoras de Pele/química , Preparações Clareadoras de Pele/toxicidade , Relação Estrutura-Atividade
13.
Molecules ; 23(9)2018 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-30216986

RESUMO

Skin-whitening ingredients are a very important part of the development of functional cosmetics and a wide variety of raw materials are used. Tyrosinase is a key enzyme in the animal melanogenic pathway that is the rate-limiting step for the production of melanin. Several synthetic and naturally occurring tyrosinase inhibitors have been studied for skin-whitening. The development of natural agents is becoming more important due to the disadvantages of synthetics such as high cytotoxicity, insufficient penetration power, and low activity. The purpose of this study was to evaluate the total phenol content (TPC), antioxidant, and tyrosinase inhibition activity of mealworm (Tenebrio molitor larvae) extract, and the subsequent optimization of the extraction condition using statistically-based optimization. The major extraction variables extraction temperature, time, and ethanol concentration were optimized using response surface methodology (RSM). The results showed that optimum extraction temperature of 88.1 °C, extraction time of 43.7 min, and ethanol concentration of 72.0 v/v%, provided the predicted maximum levels of total phenolic compounds (TPC) of 5.41 mg GAE/g dry weight (DW) and tyrosinase inhibition activity (TIA) of 82.4%. From the validation experiment, 5.61 ± 0.2 mg GAE/g dry weight (DW), tyrosinase inhibition of 79.6 ± 3.3%, and radical scavenging activity of 91.8 ± 5.1 µg/mL were found and showed to be very similar to the predicted values. These results suggest that mealworm has great potential as a source of bioactive compounds which could be used as cosmetics, food, and pharmaceutical agents.


Assuntos
Antioxidantes/isolamento & purificação , Produtos Biológicos/isolamento & purificação , Preparações Clareadoras de Pele/isolamento & purificação , Tenebrio/química , Animais , Antioxidantes/química , Produtos Biológicos/química , Larva/química , Monofenol Mono-Oxigenase/antagonistas & inibidores , Fenóis/química , Fenóis/isolamento & purificação , Preparações Clareadoras de Pele/química , Temperatura , Tempo
14.
BMC Complement Altern Med ; 18(1): 256, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30223806

RESUMO

BACKGROUND: Euphorbia supina (ES) has been widely used in folk medicine owing to its antibacterial, hemostatic, and anti-inflammatory properties. The aim of this study was to evaluate the antioxidant and skin-whitening effects of a 70% ethanol extract of ES. METHODS: The aerial parts of ES plant were extracted with 70% ethanol. The viability of B16F10 cells was evaluated by MTT assay to determine the non-toxic doses for further experiments. The tyrosinase and cellular tyrosinase activities were then measured using an enzyme-substrate assay. In addition, the expression of whitening-related proteins was measured using western blot. RESULTS: The antioxidant activity of the ES samples increased in a dose-dependent manner, as confirmed by their radical scavenging activities in the 2,2-diphenyl-1-1-picrylhydrazyl and 2,2-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) assays. The ES extract significantly reduced tyrosinase activity and melanin content in a dose-dependent manner. Furthermore, it decreased α-melanocyte stimulating hormone (MSH)-induced protein expression of tyrosinase and microphthalmia-associated transcription factor (MITF). CONCLUSIONS: Our results indicate that the ES extract attenuated α-MSH-stimulated melanin synthesis by modulating tyrosinase and MITF expression. Therefore, the ES extract could be a promising therapeutic agent to treat hyperpigmentation and as an ingredient for skin-whitening cosmetics.


Assuntos
Antioxidantes/farmacologia , Euphorbia/química , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacologia , Preparações Clareadoras de Pele/farmacologia , Animais , Antioxidantes/química , Linhagem Celular Tumoral , Melaninas/metabolismo , Camundongos , Fator de Transcrição Associado à Microftalmia/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Extratos Vegetais/química , Biossíntese de Proteínas/efeitos dos fármacos , Preparações Clareadoras de Pele/química , alfa-MSH/metabolismo
15.
Food Funct ; 9(10): 5139-5149, 2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30206602

RESUMO

Edible bird's nest (EBN), an Asian health food, contains insoluble proteins and conjugated N-acetylneuraminic acid (NANA) that are difficult to be absorbed by humans. In order to increase the nutritional value of EBN, we developed methods to digest EBN targeting the release of proteins and NANA. By using simulated gastric fluid under acidic conditions, the complex proteins were fully digested into smaller peptides, and in parallel, NANA was fully released from the conjugated form. The completely digested EBN showed better nutraceutical properties. In a skin whitening test, the EBN digest showed stronger inhibition of melanogenesis of cultured B16 cells and enzymatic activity of tyrosinase, as compared to that of undigested EBN. In addition, the EBN digest exhibited stronger osteogenic activity in cultured osteoblasts. Thus, the complete digestion of EBN could be applied to the development of a new generation of EBN health food products, including EBN drinks and skincare products.


Assuntos
Ácido N-Acetilneuramínico/química , Peptídeos/química , Saliva/química , Animais , Aves , Linhagem Celular , Digestão , Humanos , Melaninas/metabolismo , Camundongos , Ácido N-Acetilneuramínico/farmacologia , Valor Nutritivo , Osteoblastos/citologia , Osteogênese/efeitos dos fármacos , Peptídeos/farmacologia , Proteínas/química , Pele/efeitos dos fármacos , Pele/metabolismo , Preparações Clareadoras de Pele/química , Preparações Clareadoras de Pele/farmacologia
16.
Int J Mol Sci ; 19(8)2018 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-30042336

RESUMO

Caffeic acid derivatives represent promising lead compounds in the search for tyrosinase inhibitors to be used in the treatment of skin local hyperpigmentation associated to an overproduction or accumulation of melanin. We recently reported the marked inhibitory activity of a conjugate of caffeic acid with dihydrolipoic acid, 2-S-lipoylcaffeic acid (LCA), on the tyrosine hydroxylase (TH) and dopa oxidase (DO) activities of mushroom tyrosinase. In the present study, we evaluated a more lipophilic derivative, 2-S-lipoyl caffeic acid methyl ester (LCAME), as an inhibitor of tyrosinase from human melanoma cells. Preliminary analysis of the effects of LCAME on mushroom tyrosinase indicated more potent inhibitory effects on either enzyme activities (IC50 = 0.05 ± 0.01 µM for DO and 0.83 ± 0.09 µM for TH) compared with LCA and the reference compound kojic acid. The inhibition of DO of human tyrosinase was effective (Ki = 34.7 ± 1.1 µM) as well, while the action on TH was weaker. Lineweaver⁻Burk analyses indicated a competitive inhibitor mechanism. LCAME was not substrate of tyrosinase and proved nontoxic at concentrations up to 50 µM. No alteration of basal tyrosinase expression was observed after 24 h treatment of human melanoma cells with the inhibitor, but preliminary evidence suggested LCAME might impair the induction of tyrosinase expression in cells stimulated with α-melanocyte-stimulating hormone. All these data point to this compound as a valuable candidate for further trials toward its use as a skin depigmenting agent. They also highlight the differential effects of tyrosinase inhibitors on the human and mushroom enzymes.


Assuntos
Ácidos Cafeicos/química , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Preparações Clareadoras de Pele/farmacologia , Ácido Tióctico/análogos & derivados , Agaricales/enzimologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Humanos , Concentração Inibidora 50 , Melaninas/metabolismo , Melanoma/enzimologia , Pironas/farmacologia , Preparações Clareadoras de Pele/química , Ácido Tióctico/química , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores
17.
Int J Mol Sci ; 19(4)2018 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-29642633

RESUMO

l-Ascorbic acid has multifunctional benefits on skin aesthetics, including inhibition of melanin production, and is widely used in cosmetics. It, however, has low stability and poor skin penetration. We hypothesize that alkylglyceryl-l-ascorbic acid derivatives, highly stable vitamin C-alkylglycerol conjugates, would have similar anti-melanogenic activity with better stability and penetration. We test 28 alkylglyceryl-l-ascorbic acid derivatives (1-28) on theophylline-stimulated B16 melanoma 4A5 cells to determine if they inhibit melanogenesis and establish any structure-function relationships. Although not the most potent inhibitors, 3-O-(2,3-dihydroxypropyl)-2-O-hexyl-l-ascorbic acid (6, IC50 = 81.4 µM) and 2-O-(2,3-dihydroxypropyl)-3-O-hexyl-l-ascorbic acid (20, IC50 = 117 µM) are deemed the best candidate derivatives based on their inhibitory activities and low toxicities. These derivatives are also found to be more stable than l-ascorbic acid and to have favorable characteristics for skin penetration. The following structural requirements for inhibitory activity of alkylglyceryl-l-ascorbic acid derivatives are also determined: (i) alkylation of glyceryl-l-ascorbic acid is essential for inhibitory activity; (ii) the 3-O-alkyl-derivatives (2-14) exhibit stronger inhibitory activity than the corresponding 2-O-alkyl-derivatives (16-28); and (iii) derivatives with longer alkyl chains have stronger inhibitory activities. Mechanistically, our studies suggest that l-ascorbic acid derivatives exert their effects by suppressing the mRNA expression of tyrosinase and tyrosine-related protein-1.


Assuntos
Ácido Ascórbico/análogos & derivados , Melaninas/biossíntese , Melanócitos/efeitos dos fármacos , Preparações Clareadoras de Pele/síntese química , Animais , Linhagem Celular , Linhagem Celular Tumoral , Humanos , Melanócitos/metabolismo , Camundongos , Relação Quantitativa Estrutura-Atividade , Preparações Clareadoras de Pele/química , Preparações Clareadoras de Pele/farmacologia
19.
J Dermatol Sci ; 89(2): 165-171, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29191393

RESUMO

BACKGROUND: The demand for anti-melanogenic agents is increasing due to the unwanted side effects of current treatments. To find an effective anti-melanogenic agent, we used zebrafish as a whole animal model for phenotype-based drug and cosmetic discovery screening. OBJECTIVES: The aim of this study was to identify and explore a small molecule that could be used for skin-whitening cosmetics. METHODS: Using zebrafish embryos, we examined the effects of 1000 compounds on zebrafish development and pigmentation. Pigmentation production was assessed by tyrosinase (TYR) enzymatic activity and melanin contents. Pigmentation marker expression in the human melanoma cell line HMV-II was analyzed by western blot. We also tested reconstituted human skin tissue and analyzed KDZ-001 with computational molecular modeling. RESULTS: We identified three compounds that affected the pigmentation of developing melanophores in zebrafish. Among them, we identified KDZ-001, a novel anti-melanogenic agent, which strongly inhibits melanin synthesis in the developing melanophores of zebrafish, HMV-II cells, and reconstituted human skin with no toxicity. We found that KDZ-001 directly inhibits TYR enzymatic activity. Notably, computational molecular modeling of KDZ-001 suggested that its interaction with copper ions in the active site of TYR is essential for melanin synthesis, further demonstrating that KDZ-001 mainly acts as a TYR inhibitor to synthesize melanin. CONCLUSION: KDZ-001 inhibits melanin synthesis and has a potential for use in skin-whitening cosmetics.


Assuntos
Melaninas/antagonistas & inibidores , Melanócitos/efeitos dos fármacos , Monofenol Mono-Oxigenase/antagonistas & inibidores , Preparações Clareadoras de Pele/farmacologia , Pigmentação da Pele/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Humanos , Melanócitos/metabolismo , Melanóforos/efeitos dos fármacos , Melanóforos/metabolismo , Modelos Animais , Simulação de Acoplamento Molecular , Pele/citologia , Pele/efeitos dos fármacos , Pele/metabolismo , Preparações Clareadoras de Pele/química , Técnicas de Cultura de Tecidos , Peixe-Zebra
20.
Artif Cells Nanomed Biotechnol ; 46(2): 333-340, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28393568

RESUMO

Panax ginseng berry extract possess remarkable pharmacological effects on skin treatment such as anti-aging, antioxidant, promotor of collagen synthesis and alleviation against atopic dermatitis. In recent years, gold nanoparticles have gained much attention due to their extensive range of applications in particular in the field of drug delivery as a result of their biological compatibility and low toxicity. In a previous study, we designed and developed biocompatible gold and silver nanoparticles based on phytochemical profile and pharmacological efficacy of P. ginseng berry extract, we were able to reduce gold ions to nanoparticles through the process of green synthesis. However, its potential as a cosmetic ingredient is still unexplored. The aim of the present study is to investigate the moisture retention, in-vitro scavenging and whitening properties of gold nanoparticles synthesized from P. ginseng berry in cosmetic applications. Our findings confirm that P. ginseng berry mediated gold nanoparticles exhibited moisture retention capacity. In addition, MTT assay results confirmed that P. ginseng berry mediated gold nanoparticles are non-toxic to human dermal fibroblast and murine melanoma skin cells, possess scavenging activity, protect and provide alleviation against injured caused by H2O2-induced damage. In addition, P. ginseng berry mediated gold nanoparticles, significantly reduced melanin content and suppress tyrosinase activity in α-MSH-stimulated B16BL6 cells. We conclude that P. ginseng berry mediated gold nanoparticles are biocompatible and environmental affable materials and can be a potential novel cosmetic ingredient.


Assuntos
Frutas/química , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas , Panax/química , Extratos Vegetais/química , Segurança , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Sequestradores de Radicais Livres/efeitos adversos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Ouro/efeitos adversos , Humanos , Peróxido de Hidrogênio/farmacologia , Melaninas/metabolismo , Monofenol Mono-Oxigenase/metabolismo , Preparações Clareadoras de Pele/efeitos adversos , Preparações Clareadoras de Pele/química , Preparações Clareadoras de Pele/farmacologia
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