The synthesis of a water-soluble derivative of rutin as an antiradical agent

The purpose of this study was to synthesize a water-soluble derivative of rutin (compound 2) by introducing carboxylate groups on rutin's sugar moiety. The rutin derivative showed an almost 100-fold solubility increase in water. The antiradical capacity of compound 2 was evaluated using the luminol/AAPH system, and the derivative's activity was 1.5 times greater than that of Trolox®. Despite the derivative's high solubility in water (log P = -1.13), lipid peroxidation of brain homogenate membranes was very efficiently inhibited (inhibition values were only 19% lower than the inhibition values of rutin)

UVA I-protection effectiveness of bioactive compound and organic UV filters: an in vitro assessment

This research work aimed at determining the UVA effectiveness (UVA I/UV ratio), by diffuse transmittance analysis, of sunscreens developed with a bioactive substance, the rutin, associating or not with organic UVB-UVA filters incorporated at a phosphate-base O/W emulsion. Sunscreens provided conflicting and unpredictable results concerning the anti-UVA protection, specially, at the UVA I region. Possible interactions among the organic UV filters and the polyphenolic bioactive substance may have accounted with improvement or reduction of UV protection by a complex and not yet elucidated mechanism, probably regarding wavelength delocalization to superior or inferior values, by resonant molecule stabilization or destabilization

Atividade antioxidante, cito- e fototoxicidade do extrato das sementes de romã (Punica granatum L.)

In the present work, a hydroethanolic extract was prepared from the entire seeds of pomegranate [Punica granatum L. (Punicaceae)] with Cachaça, a distilled Brazilian alcoholic beverage, protected from light for an 80-hour period. The desorption curve of the seeds, presented an optimal time extraction of approximately 24 hours. The extract was divided into two samples: protected from light, (Extract 1), or not, (Extract 2). The extracts were characterized by UV-Visible absorption spectroscopy, quantification of total phenolics by the Folin-Ciocalteu method, and the antioxidant activity was determined by the DPPH quenching method. Extract 2 presented 9.8% less total polyphenols than Extract 1. The pomegranate seeds extract lost 79% of its antioxidant activity during light exposure. Extract 1 up to 3% (w/v) showed neither cyto nor phototoxicity in the Hela cells. In conclusion, Punica granatum L. seeds contain a significant total polyphenol and TEAC amount and they can be used in simple extractive process, by direct contact with Cachaça in up to 80 hours in the darkness, which gives it good coloration, taste, and smell. This extract showed neither cytotoxicity nor post-irradiation phototoxicity with solar simulator even though the extract proved photoinstable.Neste trabalho, foi realizada a extração de sementes inteiras de romã (Punica granatum L. - Punicaceae) com cachaça durante 80 horas no escuro. A curva de dessorção do extrato apresentou um tempo ótimo de extração das sementes de aproximadamente 24 horas. O extrato obtido foi dividido em duas amostras, uma delas foi mantida protegida da luz ambiente (extrato 1) e a outra não (extrato 2). As amostras foram caracterizadas por espectroscopia Ultravioleta-Visível, quantificação de polifenóis totais pelo método de Folin-Ciocalteu e pela atividade antioxidante utilizando o ensaio de inibição do radical DPPH. A exposição do extrato à luz ambiente, o fez perder 9,8% do seu teor de polifenóis totais (de 0,353 para 0,322 g.L-1). Por outro lado, a atividade antioxidante caiu a 20,7% (de 3,4 para 0,7 mM de trolox). A adição de até 3% do extrato 1 de sementes de romã não afetou significativamente a viabilidade de células epiteliais in vitro. As mesmas células tratadas com o extrato 1 e irradiadas com um simulador solar não apresentaram fototoxicidade na mesma faixa de concentração. Assim, foi possível concluir que os componentes das sementes de Punica granatum L. (romã) podem ser extraídos por contato direto com cachaça por um período de 80 horas no escuro, conferindo-lhe uma boa coloração e também propriedades organolépticas agradáveis. Tal extrato não apresenta citotoxicidade e nem fototoxicidade, embora o extrato tenha se mostrado fotoinstável.Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

The chemical synthesis of water-soluble derivatives of rutin: determination of its physico-chemical properties and evaluation of its antioxidants activities.

A rutina é um flavonol glicosídico pertencente a uma importante classe de flavonóides, sendo extensamente encontrados na natureza. Ela apresenta uma importância terapêutica em virtude de determinar a normalização da resistência e permeabilidade das paredes dos vasos capilares, além de inibir o processo de formação de radicais livres em vários estágios. O fruto do faveiro (Dimorphandra mollis Benth., uma espécie nativa brasileira) é uma das fontes para a extração em escala industrial da rutina. A sua aplicação em formas farmacêuticas para o uso externo é muito limitada devido a sua baixa solubilidade em água. Com esta finalidade, foi realizada a síntese química através da introdução de grupos carboxilatos nas hidroxilas dos grupamentos glicosídicos da molécula de rutina, utilizando-se piridina e diferentes anidridos, sendo eles: o succínico, o ftálico e o 2-fenil-glutárico à temperatura de 70 ºC por 24 horas. Estes três derivados sintetizados foram purificados em papel cromatográfico e caracterizados em 2 sistemas de proporções diferentes de eluentes. Além disso, foi feito um estudo comparativo entre as suas propriedades físico-químicas e as da rutina pela determinação da solubilidade e do coeficiente de extinção molar. Desta forma, avaliou-se a atividade antioxidante destes derivados com relação a rutina utilizando 2 ensaios diferentes, como a determinação de malondialdeído pela autoxidação do tecido cerebral e produção de radicais peroxilas pela termólise de um azo-iniciador, com os seus respectivos padrões de referência, o α-tocoferol e o Trolox. O resultado do ensaio de solubilidade indicou que a rutina succinil, a ftaloil e a fenil-glutaroil foram cerca de 800, 85 e 5,5 vezes mais solúvel em água que a rutina. Já em relação aos outros ensaios verificou-se que os derivados sintetizados continuaram apresentando atividade antioxidante e absorvendo luz em seu pico máximo próximo de 392nm, o que mostrou pouca modificação química no núcleo flavonóide. No ensaio de anti-radicais, a rutina ftaloil foi entre os derivados hidrossolúveis a que apresentou um melhor resultado devido a sinergia do anel aromático com o núcleo flavonóide em seqüestrar radicais livres.Rutin is a glycoside flavonol which belongs to an important class of flavonoids, being extensively found in the nature. It presents a therapeutical importance due to improve the resistance and permeability of capillaries vessels, and is able to suppress free radical processes in some stages. The fruit of the faveiro (Dimorphandra mollis Benth., a Brazilian native species) is one of the sources for the extration in industrial scale of the rutin. Its application in pharmaceutical forms for external use very is limited because it has low solubility in water. With this purpose, it was done the chemical synthesis introducing carboxylate groups on sugar moiety of rutin using pyridin and different anhydrides, such as: succinic, phtalic and the 2-phenyl glutaric at 70 ºC for 24 hours. These three synthesized derivatives had been purificated in chromatographic paper and characterized in 2 systems of different ratios of eluents. Moreover, a comparative study among their physico-chemical properties and of the rutin for the determination of the solubility and the molar extinction coefficient. With this in mind, it was evaluated antioxidant activity of these derivatives with regard to rutin using 2 different assays, as the determination of malondialdehyde by the brain homogenate autoxidation and generation of peroxyl radicals by the thermolysis of a azo compound, with its respective reference standards: α-tocopherol and Trolox. The result of the solubility assay indicated that the succinyl, the phtaloyl and the phenyl glutaroyl rutin had been about 800, 85 and 5,5 times, respective, more soluble in water that the rutin. In respect to relationship to the other assays it was verified that the synthesized derivatives had continued presenting antioxidant activity and absorbing light in its maximum peak next to 392nm, showing that chemical modifications in the flavonoid nucleus had not been made significant. In the assay of anti-radicals, the phtaloyl rutin was the water-soluble derivative what it presented one better result, due one the presence of the aromatic ring that can enhanced the radical-scavenging efficiencies together to the flavonoid nucleus

Synthesis and in vitro safety evaluation of rutin and rutin succinate aiming their incorporation into effective sunscreens associated with chemical and physical filters

A tendência atual do mercado cosmético é desenvolver produtos que contenham insumos de origem vegetal. O objetivo deste trabalho foi a aplicação da Tecnologia da Química Verde na síntese da rutina visando o aumento da estabilidade dessa em formulações cosméticas com sua eficácia antioxidante e fotoprotetora. Realizou-se a síntese química por meio da introdução de grupos carboxilatos às hidroxilas do dissacarídeo na molécula de rutina, gerando como produto final o succinato de rutina. Este derivado e/ou a rutina foram incorporados em 74 formulações-teste e, selecionadas 12 (sistemas emulsionados O/A), após serem submetidas à Avaliação Preliminar de Estabilidade (APE) e ao Teste de Estabilidade Acelerada (TEA), sob variações de temperatura e umidade. Utilizou-se agentes emolientes e silicones para facilitar a solubilização e/ou dispersão dos filtros químicos e físicos. A segunda etapa deste trabalho foi a avaliação da segurança do succinato de rutina, tendo como padrão a rutina, por meio do método alternativo de toxicidade in vitro, o XTT. Após o screening das concentrações ensaiadas, as que apresentaram menor nível de morte celular foram respectivamente, 0,1% ou 1 mg/mL (rutina) e 0,4% ou 4 mg/mL (succinato de rutina). Segundo os resultados do TEA, as formulações contendo succinato de rutina associada ou não aos filtros solares em ambas as bases cosméticas (A - Crodafos®CES + Uniox®C e B - Hostacerin®SAF) foram selecionadas para a continuidade do Teste de Estabilidade Normal (TEN). Neste teste, as emulsões fotoprotetoras foram avaliadas frente aos parâmetros: propriedades organolépticas (aspecto, cor e odor), aspectos físico-químicos (medição de pH e de viscosidade) e funcionais (atividade antirradicalar e eficácia fotoprotetora in vitro). Os resultados apresentados pela formulação MS (succinato de rutina associado aos filtros químicos e físico) foram: homogeneidade, a não modificação de cor e odor em temperatura ambiente, a não alterações significativas de valores de pH, de área de histerese, de atividade antirradicalar e de FPS. Esta estabilidade ocorreu principalmente quando incorporada à base cosmética A num período de 90 dias em 45ºC e 75% de umidade, 5ºC e 25ºC. Concluiu-se que a funcionalidade desta associação MS mostrou-se mais estável, mantendo a eficácia quanto à proteção solar e dentro de suas características reológicas poderia ser a mais bem aceita pelo consumidor.The current cosmetic market trend is to develop products containing vegetables raw materials. This work proposed to use the Technology of Green Chemical to increase the rutin stability in cosmetic formulas as regards of its antioxidant and photoprotective properties. The chemical synthesis was realized by the introduction of carboxylate groups on sugar moiety of rutin producing in rutin succinate. This derivative and/or rutin were incorporated into 74 test formulas. After the undergoing to preliminary and accelerated stabilities under different temperature and humidity conditions were selected 12 formulas (O/W emulsions). Emollient agents and silicones were used to improve the solubility and/or dispersion of the chemical and physical filters. The second stage of this work was to evaluate the safety of rutin succinate, rutin used as an internal standard, using the alternative method of in vitro toxicity, the XTT. After the screening of tested concentrations, the concentrations of the samples with the lowest level of cell death were 0.1% or 1 mg/mL (rutin) and 0.4% or 4 mg/mL (rutin succinate), respectively. According to results obtained in accelerated stability testing, the formulations containing rutin succinate in combination or not with UV filters in both O/W emulsions (A - Crodafos®CES + Uniox®C and B - Hostacerin®SAF) were selected for the long term stability test. In this test the sunscreens were evaluated in the following parameters: the organoleptic properties (appearance, color and odor), physico-chemical aspects (pH value and viscosity) and functional (antiradicalar activity and in vitro photoprotection efficacy). The results presented by the MS formula (rutin succinate associated with physical filter and chemical filters) were: uniformity, stability of color and odor at room temperature and showed no significant difference, as well stability in: pH and SPF (Sun Protection Factor) values, hysteresis area, antiradicalar activity. These results were observed mainly when it was incorporated to O/W emulsion A (90 days of analyses at 45°C and 75% humidity, 5°C and 25°C). It was observed the functionality of MS association was more stable, maintaining photoprotective efficacy and within their rheological properties could be more accepted by consumers

Development and Stability Evaluation of Liquid Crystal-Based Formulations Containing Glycolic Plant Extracts and Nano-Actives

Emulsions are of great use in cosmetic formulations due to their stability. The aim of this work was to develop and assess organoleptic, physicochemical, and microscopic properties of four auto-emulsifiable oil-in-water formulations. Such formulations were developed containing 4.0% cetearyl alcohol, dicetyl phosphate, and ceteth-10 phosphate (Formulation A), nano-actives obtained from safflower, coconut, and clove oils (Formulation B); a mixture of glycolic extracts from Centella asiatica leaves, Aesculus hippocastanum seeds, and Hamamelis virginiana leaves (Formulation C); association between the nano-actives and glycolic extracts described above (Formulation D). The formulations were trialed for 90 days under the normal stability test. The developed formulations were considered all stable and homogeneous, with liquid crystals possibly being formed. Organoleptic parameters and pH of Formulations A and B remained unchanged, but the color of Formulations C and D changed due to the natural color of the glycolic extracts used. It can be concluded that the formation of liquid crystals increased the stability of the formulations, and future tests should be carried out in order to assess the rheological properties and hydration potential of the developed formulations

Bioactive Peptides: Applications and Relevance for Cosmeceuticals

Peptides found in skin can act by different mechanisms of action, being able to function as epidermal or nervous growth factors or even as neurotransmitters. Due to the vast functionality of these compounds, there is growing research on bioactive peptides aimed at investigating their uses in products developed for stimulating collagen and elastin synthesis and improving skin healing. Thus, a literature search on applications of the most common bioactive peptides used in cosmeceuticals was carried out. There is a lack of proper reviews concerning this topic in scientific literature. Nine peptides with specific actions on body and facial dysfunctions were described. It could be noted while searching scientific literature that studies aimed at investigating peptides which prevent aging of the skin are overrepresented. This makes searching for peptides designed for treating other skin dysfunctions more difficult. The use of biomimetic peptides in cosmetic formulations aimed at attenuating or preventing different types of skin dysfunctions is a topic where information is still lackluster. Even though research on these compounds is relatively common, there is still a need for more studies concerning their practical uses so their mechanisms of action can be fully elucidated, as they tend to be quite complex

Assessment of Functional Stability of Photoprotective Formulations Containing Rutin Succinate

The aim of this study was to evaluate physicochemical and functional stability of two different self-emulsified oil/water (O/W) systems. Each system contained 0.4% w/w rutin succinate, which was associated or not with the photo-unstable chemical (7.5% w/w of 2-ethylhexyl 4-methoxycinnamate and 3.0% w/w of 2-hydroxy-4-methoxybenzophenone) or physical filters (3.0% w/w titanium dioxide). A Normal Stability Test was carried out with the formulations containing rutin succinate (S) associated either with sunscreens (MS) or not (M) for 90 days. The formulation systems were assessed for organoleptic, functional, physicochemical and rheological behavior parameters. The MS formulation was found to be homogenous and had no significant alterations of pH, hysteresis area, antiradical activity or Sun Protection Factor values. Such stability was mainly observed when the formulation was incorporated into base cream A. The ability of chemical filters to resist degradation caused by UV radiation in the presence of rutin succinate preventing lipid peroxidation by entrapment of initiator radicals is a mechanism that might explain the results. The combination of rutin succinate to chemical filters improved formulation functionality, as it led to a more stable formulation which maintained the effectiveness of the added sunscreens. Consumer acceptance could be improved, considering that film formation and rheological spreadability characteristics of the tested formulation are better than those of traditional formulations

Novas metodologias analíticas para avaliação da eficácia fotoprotetora (in vitro) – revisão

Atualmente, são utilizadas técnicas in vitro e in vivo para a avaliação do Fator de Proteção Solar (FPS) e do Fator de Proteção de UVA (FPA). O presente trabalho propõe a revisão das técnicas para as avaliações desses fatores in vitro preconizadas por FDA (Food and Drug Administration Agency) e COLIPA (European Cosmetic, Toiletry and Perfumery Association). O enfoque maior foi direcionado à análise espectrofotométrica de soluções diluídas e à espectrofotometria de reflectância com esfera integrada. Palavras-chave: Espectrofotometria. Fotoproteção. UVA. UVB. Revisão. ABSTRACT New analytical methods for photoprotection effectiveness testing (in vitro) – a review Currently, both in vitro and in vivo techniques are used to measure Sun Protection Factor (SPF) and UVA Protection Factor (APF). This paper reviews the in vitro techniques to test these factors, recommended by the FDA (USA Food and Drug Administration) and COLIPA (European Cosmetic, Toiletry and Perfumery Association). The main focus is on the spectrophotometric analysis of dilute solutions and the use of reflectance spectrophotometry with an integrating sphere. Keywords: Spectrophotometry. Photoprotection. UVA. UVB. Review