Analysis of the toxicological and pharmacokinetic profile of Kaempferol-3-O-β-D-(6"-E-p-coumaryl) glucopyranoside - Tiliroside: in silico, in vitro and ex vivo assay / Análise do perfil toxicológico e farmacocinético de Kaempferol-3-O-β D-(6"-E-p-cumaril) glucopiranosídeo - Tilirosídeo: ensaio in silico, in vitro e ex vivo

Tiliroside is a glycosidic flavonoid present in many plants species including Helicteres velutina K. Schum (Malvaceae sensu lato), commonly known in Brazil as "pitó". This molecule has been shown to have many biological activities, however no study has been carried out to investigate the toxicity of this substance. The present work aimed to evaluate the possible cellular toxicity in silico, in vitro and ex-vivo of the kaempferol-3-O-β-D-(6”-E-p-coumaroyl) glucopyranoside (tiliroside), through chemical structure analysis, toxicity assessment and predictive bioactive properties, using human samples for in vitro and ex-vivo tests. The in silico analysis suggests that tiliroside exhibited great absorption index when penetrating biological membranes. In addition, it also displayed considerable potential for cellular protection against free radicals, and anticarcinogenic, antioxidant, antineoplastic, anti-inflammatory, anti-hemorrhagic and antithrombotic activities. The assessment of the hemolytic and genotoxic effects of tiliroside showed low hemolysis rates in red blood cells and absence of cellular toxicity in the oral mucosa cells. The data obtained indicate that this molecule could be a promising therapeutic approach as a possible new drug with biotechnological potential.

O tilirosídeo é um flavonóide glicosídico presente em muitas espécies de plantas, incluindo Helicteres velutina K. Schum (Malvaceae sensu lato), conhecida no Brasil como “pitó”. Esta molécula mostrou ter muitas atividades biológicas, porém nenhum estudo foi realizado para investigar a toxicidade dessa substância. O presente trabalho teve como objetivo avaliar a possível toxicidade celular in silico, in vitro e ex-vivo do kaempferol-3-O-β-D- (6 ”-Ep-coumaroil) glucopiranosídeo (tilirosídeo), por meio de análises de estrutura química, toxicidade avaliação e propriedades bioativas preditivas, utilizando amostras humanas para testes in vitro e ex-vivo. A análise in silico sugere que o tilirosídeo exibe bom índice de absorção para penetrar nas membranas biológicas. Além disso, apresentou considerável potencial de proteção celular contra os radicais livres e com atividades anticarcinogênica, antioxidante, antineoplásica, antiinflamatória, anti-hemorrágica e antitrombótica. A avaliação dos efeitos hemolíticos e genotóxicos do tilirosídeo mostrou baixas taxas de hemólise nas hemácias e ausência de toxicidade em células da mucosa oral. Os dados obtidos indicam que esta molécula pode possuir uma abordagem terapêutica promissora como uma possível nova droga com potencial biotecnológico.

In vitro antifungal activity and phytochemical characterization of Eugenia uniflora, Libidibia ferrea and Psidium guajava

The aim of this study was evaluate the in vitro antifungal activity of crude extracts from Eugenia uniflora, Libidibia ferrea and Psidium guajava. The extracts were obtained by turbo-extraction using water (AQ) or acetone-water (AC-W) (7:3, v/v) as solvents and lyophilized to obtain the crude extracts (CE). The CE were characterized by UV-Vis, TLC and HPLC. The activity of CEs was investigated against clinical isolates of Candida spp. and the Minimum Inhibitory Concentration (MIC), MIC50 and MIC90 were determinated. The analysis by TLC showed that all CEs presented polyphenols (flavonoids and tannins). The CEs from E. uniflora showed higher amount of polyphenols (30.35 ± 2.15%, AC-W) and the HPLC analysis revealed the tannins in all extracts. The CEs of E. uniflora showed MIC range from 1.9 to 500.0 µg/mL, and lower values of MIC50 and MIC90 against non-albicans Candida isolates. Regarding L. ferrea and P. guajava, the results showing MIC from 3.9 to 1000.0 µg/mL (CE-AQ) against C. albicans. The results demonstrate antifungal performance from CE against various species of Candida spp., suggesting that the herbal species may be use as new potential antifungal agents. Additionally, the polyphenol content can play a pivotal role in the antifungal properties of CE.

Combined use of borneol or menthol with labrasol promotes penetration of baicalin through rabbit cornea in vitro

The permeability of most drugs through the eyes is very limited, so finding safe and effective penetration enhancers is of high importance in current ophthalmology research. In this paper, we use a new approach that integrates Chinese and Western medicine to improve the corneal permeability of baicalin, a water- and fat-insoluble target drug, in vitro. Rabbits were divided into three groups. The first group was dosed with borneol [0.05%, 0.1%]. menthol [0.1%, 0.2%], or Labrasol [1%, 2%] individually, the second was dosed with a combination of Labrasol with either borneol or menthol, and the third group received a control treatment. Compared with the control treatment, borneol, menthol, or Labrasol alone clearly improved the permeability of baicalin in vitro. Furthermore, the penetrating effects were significantly increased by combining the application of Labrasol with menthol or borneol. Among the various combined penetration enhancers, 0.1% borneol with 2% Labrasol achieved the best apparent permeability, approximately 16.35 times that of the control. Additionally, the calculation of corneal hydration level and the Draize test demonstrated the safety of these penetration enhancers to the rabbit corneas in vivo. This study confirms that the combined use of borneol or menthol, compounds both derived from Chinese herbs, with Labrasol can improve the corneal permeability of waterand fat-insoluble drugs

Efecto antiinflamatorio y antioxidante de los flavonoides de las hojas de Jungia rugosa Less (matico de puna) en un modelo experimental en ratas / Antiinflammatory and antioxidant effects of Jungia rugosa Less (matico de puna) leaves' flavonoids in rats

Objetivos: Evaluar la actividad antiinflamatoria y antioxidante de la fracción flavónica extraída de las hojas de Jungia rugosa Less. Diseño: Experimental. Lugar: Facultades de Medicina y Farmacia y Bioquímica, Universidad Nacional Mayor de San Marcos, Lima, Perú. Material biológico: Fracción flavónica extraído de las hojas de Jungia rugosa Less y ratas. Intervenciones: Las hojas de Jungia rugosa Less fueron recolectadas en el cerro Condorcunca, a 3 500 msnm, distrito de Quinua, departamento de Ayacucho. La actividad antiinflamatoria fue evaluada in vivo usando el método de edema plantar inducido por carragenina y en sangre se cuantificó los niveles séricos de interleuquinas 1, 6 y proteína C reactiva (PCR); también, se indujo el granuloma, según Sedwicks, evaluándose por histopatología. La actividad antioxidante fue evaluada in vitro mediante la neutralización del radical 1,1-difenil-2-picril-hidrazilo (DPPH). Principales medidas de resultados: Actividad antiinflamatoria y antioxidante. Resultados: La inflamación disminuyó en 43,8 por ciento, y los niveles de interleuquinas 1, 6 y PCR lo fueron en 80 por ciento, 90 por ciento y 78 por ciento, respectivamente, al ser comparados con el control (p<0,05), siendo el efecto dosis dependiente, y brindó un 97,7 por ciento de inhibición de radicales DPPH. Conclusión: Se ha demostrado que la fracción flavónica extraída de las hojas de Jungia rugosa Less es antiinflamatoria y antioxidante.

Objectives: To determine anti-inflammatory and antioxidant activities of Jungia rugosa Less leaves flavonesÆ fraction. Design: Experimental. Setting: Faculties of Medicine and Pharmacy and Biochemistry, National University of San Marcos, Lima, Peru. Biological material: Flavones fraction extracted from Jungia rugosa Less leaves and rats. Interventions: Jungia rugosa Less leaves collected in CondorcuncaÆs hill at 3 500 m.a.s.l., Quinua district, Ayacucho department. The anti-inflammatory activity was assessed in vivo in carrageenan-induced paw edema model and 1, 6 interleukins serum levels and C reactive protein (CRP) were measured in blood; granuloma was induced according to Sedwicks and studied by histopathology. The antioxidant effect was investigated in vitro by 1,1- diphenyl-2-picrylhydrazyl (DPPH) radical neutralization. Main outcome measures: Anti-inflammatory and antioxidant effects. Results: Inflammation reduced in 43,8 per cent and 1,6 interleukins and CRP levels decreased respectively 80 per cent, 90 per cent and 78 per cent compared to control, in dose-dependent effect (p<0,05), with 97,7 per cent DPPH radicals inhibition. Conclusions: Flavones fraction extracted from Jungia rugosa Less leaves is anti-inflammatory and antioxidant.

El consumo de manzanas contribuye a prevenir el desarrollo de enfermedades cardiovasculares y cáncer: antecedentes epidemiológicos y mecanismos de acción / Apple consumption helps to prevent cardiovascular diseases and cancer: epidemiology and mode of action

Consumption of fruit and vegetables has the potential to reduce non-transmissible diseases (NTD), such as cardiovascular diseases (CVD) and cancer, which are major public health concerns. Chile is a major apple producer and exporter in the world. Its production is concentrated in the sixth (O'Higgins) and seventh (Maule) regions of Central Chile. Phenolics and flavonoids are responsible for apple's high antioxidant activity. Many epidemiologic studies have shown that a diet rich in apples can reduce cardiovascular events (myocardial infarct and stroke) and some type of cancers. The mechanisms involved are not well understood. Nevertheless, antioxidants are key-players. Some of their in-vitro activities are inhibition of low-density lipoprotein (LDL) oxidation, cholesterol levels reduction, endothelium protection, reduction of neoplastic cells proliferation and apoptosis activation. Consequently, daily apple consumption campaigns in the country should be implemented, as well as funding research focused on molecular mechanisms involved in its antioxidant activity.

Las enfermedades no transmisibles (ENT), especialmente las cardiovasculares (ECV) y el cáncer, representan un grave problema de salud pública. Es conocido que el consumo de frutas y hortalizas disminuye el riesgo de sufrir dichas enfermedades. El manzano (Malus domestica Borkh.) se cultiva en Chile en una amplia zona geográfica, concentrándose principalmente en las regiones sexta y séptima. La actividad antioxidante de la manzana se debe principalmente a su contenido en fenoles y flavonoides. Varios estudios epidemiológicos han mostrado que el consumo de manzanas puede prevenir el desarrollo de ECV (infarto agudo de miocardio y enfermedad cerebro vascular) y ciertos tipos de cáncer. Los mecanismos por los cuales se producen dichos efectos, no están totalmente aclarados, sin embargo la participación de los antioxidantes es fundamental. Entre los principales hallazgos se han descrito, en relación a ECV: inhibición de la oxidación de low-density lipoprotein (LDL), disminución de colesterol total y protección de endotelio; y en relación a cáncer: disminución de la proliferación de células neoplásicas y activación de la apoptosis de las mismas. Debido al incuestionable efecto protector para la salud humana que presenta la ingesta de manzana, se deben impulsar estrategias que apunten a incentivar su consumo diario en el país. Asimismo, se deben seguir estudiando los principios activos y los mecanismos moleculares.