The dietary supplement of Ginkgo biloba: a comprehensive review of its potential interactions based on pre-clinical and clinical evidences / El suplemento dietético de Ginkgo biloba: una revisión exhaustiva de sus posibles interacciones basada en evidencias clínicas y preclínicas

This review present Gingko biloba (GB) interactions, based on clinical and pre-clinical presentations. Literature was retrieved using databases; ScienceDirect, PubMed, Google scholar, Web of Science, Scopus etc. 14/45 interactions were found with clinical presentations. More interactions (80%) were reported with drugs followed by herbs (11.1%), and nutraceuticals (6.7%) with major mechanisms of interaction observed as; inhibition of Cytochrome metabolizing enzymes (44.4%) and platelet-activating factor (PAF) i.e. 15.6%. Major clinical features were; increased bleeding (eye, parietal), hematomas (subdural), and seizures as well as increased blood pressure, priapism, loss of infection/antiviral failure, and coma. Drugs with major interactions belonged to anti-platelet/anti-coagulant and NSAIDs. Synergistic effects were observed for GB vs herbs (except cannabis which showed rhabdomyolysis), foods, and nutraceuticals (except pyridoxine where neurotoxicity was seen). GB use should be monitored and the patient may seek proper advice from a healthcare professional.

Esta revisión presenta las interacciones de Gingko biloba (GB), basadas en presentaciones clínicas y preclínicas. La literatura se recuperó utilizando bases de datos; ScienceDirect, PubMed, Google Scholar, Web of Science, Scopus, etc. Se encontraron 14/45 interacciones con presentaciones clínicas. Se informaron más interacciones (80%) con fármacos seguidos de hierbas (11,1%) y nutracéuticos (6,7%) con los principales mecanismos de interacción observados como; inhibición de las enzimas metabolizadoras del citocromo (44,4%) y factor activador de plaquetas (PAF), es decir, 15,6%. Las principales características clínicas fueron; aumento de sangrado (ojo, parietal), hematomas (subdural) y convulsiones, así como aumento de la presión arterial, priapismo, pérdida de infección / insuficiencia antiviral y coma. Los fármacos con interacciones importantes pertenecían a los antiplaquetarios/anticoagulantes y los AINE. Se observaron efectos sinérgicos para GB frente a hierbas (excepto cannabis que mostró rabdomiólisis), alimentos y nutracéuticos (excepto piridoxina donde se observó neurotoxicidad). Se debe controlar el uso de GB y el paciente puede buscar el asesoramiento adecuado de un profesional de la salud.

Evaluación de las condiciones de crecimiento celular para la producción de astaxantina a patir de la microalga Haematococcus pluvialis / Evaluation of Cell Growth Conditions for the Astaxanthin Production as of Haematococcus pluvialis Microalgae

Resumen En la actualidad la astaxantina de origen natural es uno de los pigmentos carotenoides con importantes aplicaciones en la industria alimenticia, farmacéutica y cosmética, debido a sus grandes propiedades dentro de las que se destaca su gran poder antioxidante, efecto preventivo del cáncer, incremento de la respuesta inmune, inhibición de los radicales libres entre muchas otras. Haematococcus pluvialis es una microalga verde de agua dulce y es una de las fuentes naturales con mayor producción de astaxantina ya que es capaz de acumular hasta un 3% de astaxantina en peso seco. El objetivo del presente trabajo fue determinar el medio de cultivo y las condiciones óptimas para el crecimiento y la producción de astaxantina a partir de Haematococcus pluvialis. La influencia de diferentes factores como el pH, temperatura, agitación, aireación CO2 e iluminación favorecen el crecimiento celular, al darle un ambiente óptimo a la microalga. Para determinar las condiciones nutricionales óptimas, se evaluó el efecto de diferentes medios de cultivo (BBM, OHM, RM) en Birreactores de 500mL con 350mL de medio y 1x104cel/ml de inóculo en fase exponencial, las condiciones de cultivo empleadas fueron: pH. 6.7 a 7, CO2 al 5%, fotoperiodo de 16 horas luz 8 oscuridad, irradianza 70μE/m2s; Los resultados mostraron que el mayor crecimiento o producción celular se obtuvo en el medio RM con 7,5 x 105 cel/ml en el día 36, y la mayor producción de astaxantina se obtuvo en el medio RM con una concentración de 8.3 μg/ml en el tratamiento 4.

Abstract Currently astaxanthin of natural origin is one of the carotenoids with important applications in the food, pharmaceutical and cosmetics, due to their large properties within its powerful antioxidant, cancer preventive effect, increase the immune response, inhibiting free radicals among many others. Haematococcus pluvialis is a freshwater green microalgae and is one of the largest natural sources of astaxanthin production as it is able to accumulate up to 3% astaxanthin by dry weight. The aim of this study was to determine the culture medium and the optimal conditions for growth and production of astaxanthin from Haematococcus pluvialis. The influence of different factors such as pH, temperature, agitation, aeration and lighting, CO2, promote cell growth, by giving an optimal environment to microalgae. To determine the optimal nutritional conditions for cell growth the effect of different culture media (BBM, OHM, RM) in bioreactors of 500 ml with 350mL of medium and 1x104 cells/ml inoculum was evaluated in exponential phase, the culture conditions employed they were: pH. 6.7 to 7, 5% CO2, 16 hours photoperiod Light 8 dark, irradiance 70 μE / m2s; The results showed that the highest growth and cell reproduction was obtained in the middle RM with 7.5 x 105 cells /ml on day 36, and increased production of astaxanthin was obtained in the middle RM with a concentration of 8.3 ug / ml in the treatment 4.

Un método basado en la PCR para la identificación rápida de levaduras acumuladoras de astaxantina (Phaffia spp. ) / PCR-based method for the rapid identification of astaxanthin-accumulating yeasts (Phaffia spp.)

It has been recently found that the natural distribution, habitat, and genetic diversity of astaxanthin-producing yeasts (i.e. Phaffia rhodozyma, synonym Xanthophyllomyces dendrorhous) is much greater than previously thought. P. rhodozyma is biotechnologically exploited due to its ability to produce the carotenoid pigment astaxanthin and thus, it is used as a natural source of this pigment for aquaculture. P. rhodozyma was also capable of synthesizing the potent UVB sunscreen mycosporine-glutaminol-glucoside (MGG). Therefore, further environmental studies are needed to elucidate its ecological aspects and detect new potential strains for the production of astaxanthin and MGG. However, obtaining new isolates of P. rhodozyma and related species is not always easy due to its low abundance and the presence of other sympatric and pigmented yeasts. In this work we report a successful development of a species-specific primer which has the ability to quickly and accurately detecting isolates representing all known lineages of the genus Phaffia (including novel species of the genus) and excluding closely related taxa. For this purpose, a primer of 20 nucleotides (called PhR) was designed to be used in combination with universal primers ITS3 and NL4 in a multiplex amplification. The proposed method has the sensitivity and specificity required for the precise detection of new isolates, and therefore represents an important tool for the environmental search for novel astaxanthin-producing yeasts.

Recientemente, se ha encontrado que la distribución natural, el hábitat y la diversidad genética de levaduras productoras de astaxantina (p. ej., Phaffia rhodozyma, sinónimo Xanthophyllomyces dendrorhous) son mucho mayores de lo que se pensaba. P. rhodozyma se explota biotecnológicamente debido a su capacidad para producir el pigmento carotenoide astaxantina y, por lo tanto, se utiliza como una fuente natural de este pigmento para la acuicultura. También se encontró que esta levadura es capaz de sintetizar el potente protector solar UVB micosporina-glutaminol-glucósido (MGG). Por lo tanto, más estudios ambientales para dilucidar sus aspectos ecológicos y detectar nuevas cepas potenciales productoras de astaxantina y MGG son necesarios. Sin embargo, la obtención de nuevos aislamientos de P. rhodozyma y especies relacionadas no siempre es fácil debido a su baja abundancia y a la presencia de otras levaduras simpátricas y pigmentadas. En este trabajo se describe el desarrollo exitoso de un cebador especie-específico que tiene la capacidad de detectar rápidamente y con precisión cepas representativas de todos los linajes del género Phaffia previamente reportados (incluyendo nuevas especies del género) y excluir especies estrechamente relacionadas. Para ello, se diseñó un cebador de 20 nucleótidos (denominado PhR) para ser utilizado en combinación con los cebadores universales ITS3 y NL4 en una amplificación multiplex. El método propuesto tiene la sensibilidad y la especificidad requerida para la detección precisa de nuevos aislamientos y, por lo tanto, representa una importante herramienta para la búsqueda ambiental de nuevas levaduras productoras de astaxantina.

The effect of astaxanthin on resistance of juvenile prawns Macrobrachium nipponense (Decapoda: Palaemonidae) to physical and chemical stress / Efecto de la astaxantina en la resistencia al estrés físico y químico de los langostinos jóvenes de Macrobrachium nipponense (Decapoda: Palaemonidae)

In recent years, the use of new scientific techniques has effectively improved aquaculture production processes. Astaxanthin has various properties in aquacultureand its antioxidant benefits have been closely related to stress resistance; besides, it is an essential factor for growth in many crustaceans and fish. The objective of this study was to evaluate the resistance of prawn (Macrobrachium nipponense) fed diets containing different amounts of astaxanthin (AX) to the shock and stress of differentphysicochemical environments. A 70-day trial was conducted to evaluate the effect of supplementation of a source of astaxanthin (Carophyll Pink, 10% astaxanthin, w/w, Hoffman-La Roche, Switzerland) at various levels in the diet of M. nipponense juveniles. Four dry diets were prepared: AX0 without astaxanthin, AX50 with 50mg/kg, AX100 with 100mg/kg, and AX150 with 150mg/kg astaxanthin. The feeding trial was conducted in a recirculation water system consisting of 12 fiberglass tanks (1 000L) used for holding prawns. Three replicate aquaria were initially stocked with 36org/m² per tank. During the trial, prawns were maintained on a 12:12-h light:dark photoperiod with an ordinary incandescent lamp, and the water quality parameters were maintained as follows: water temperature, 25-26°C; salinity, 1g/L; pH, 8.5-8.8; dissolved oxygen, 6.0-6.5mg/L; and ammonia-nitrogen, 0.05mg/L. Incorporation of AX, production output, and physiological condition were recorded after 10 weeks of feeding. At the end of the growing period, the prawns were exposed to thermal shock (0°C), ammonia (0.75mg/L), and reduced oxygen (0.5mg/L). The time to lethargyand the time to complete death of the prawns were recorded. The results showed that control prawns had the shortest time to lethargy and death compared with prawns subjected to the other treatments. The results of this study have shown that the amount of muscle tissue and gill carotenoids in prawn fed with an AX150 diet showed greater reduction than those exposed to other treatments. It is possible that higher levels of astaxanthin in the body under oxygen reduction stress can be beneficial forprawns. These results suggest that male prawns showed lethargy earlier than females, and the percentage of carotenoid reduction in muscle and gill tissues was higher inmales. Rev. Biol. Trop. 62 (4): 1331-1341. Epub 2014 December 01.

En años recientes, la utilización de nuevas técnicas científicas ha tenido un efecto importante en mejorar los procesos de producción en acuicultura. La astaxantina tiene varias propiedades en la acuicultura y sus propiedades antioxidantes se encuentran estrechamente relacionadas con la resistencia al estrés. La astaxantina en muchos crustáceos y peces es un factor esencial para el crecimiento. El objetivo de este estudio fue evaluar la resistencia del langostino (Macrobrachium nipponense) alimentado con dietas conteniendo diferentes cantidades de astaxantina (AX), bajo diferentes condiciones de estrés ambiental. Un ensayo de 70 días fue llevado a cabo para evaluar el efecto de la suplementación de fuentes de astaxantina (Carophyll Pink, 10 % astaxanthin) en varios niveles en la dieta de jóvenes de M. nipponense. Cuatro dietas fueron preparadas: AX0 sin astaxantina, AX50 con 50mg/kg, AX100 con 100mg/kg y AX150 con 150mg/kg de astaxantina. Los ensayos de alimentación fueron conducidos en un sistema de recirculación de agua consistente en 12 estanques de fibra de vidrio (1 000L). Tres replicas fueron sembradas con 36org/m2 por tanque. Durante el experimento los langostinos fueron mantenidos con un fotoperiodo de 12:12 luz:oscuridad con lámparas incandescentes y los parámetros de la calidad del agua fueron mantenidos a 25-26°C la temperatura, 1 g/L la salinidad, 8.5-8.8 el pH, 6.0-6.5 mg/L el oxígeno y 0.05mg/L el nitrógeno amoniacal. La incorporación de la astaxantina, producción y condiciones fisicoquímicas fueron registradas después de 10 semanas de alimentación. Al final del periodo de crecimiento, los langostinos fueron expuestos a un shock térmico (0°C), amonio (0.75mg/L) y reducción de oxígeno 0.5 mg/L. El tiempo de letargia y el tiempo de muerte fueron registrados. Se encontró que la dieta con la mayor concentración de astaxantina (150mg/kg) presentó el mayor tiempo de letargia y la mayor concentración en branquias y músculo en el langostino M. nipponense.

Producción de Astaxantina en Haematococcus pluvialis bajo diferentes condiciones de estrés / Astaxanthin Production in Haematococcus pluvialis under different stress conditions

Las microalgas son fuente de un gran número de compuestos bioactivos de interés industrial, como los carotenoides que se utilizan como colorantes naturales en alimentación animal y humana, así como en la industria farmacéutica, cosmética y en la acuicultura. Además se han propuesto como agentes efectivos en la prevención de una variedad de enfermedades, debido a su capacidad antioxidante, inmunoregulaora, anti-inflamatoria y anti-cancerígena. El ketocarotenoide astaxantina es el más importante desde el punto de vista biotecnológico. Hoy la mayor cantidad de astaxantina es producida por síntesis química y es vendida a un precio de US $2500/kg. El alto precio y el incremento en la demanda para este compuesto, especialmente de origen natural, en las diferentes industrias, hace que sea de interés la producción astaxantina a partir de microalgas como el Haematococcus pluvialis, que acumula cantidades importantes (más del 4%/g de peso seco) y de mejor calidad que las obtenidas por otras fuentes como levaduras y plantas. La acumulación del pigmento en H. pluvialis ocurre durante la transformación de la microalga desde el estado vegetativo (fase verde) a aplanospora (fase roja) cuando cesa su crecimiento en la fase estacionaria. Los tipos de estrés que inducen a la acumulación de astaxantina son temperatura, intensidad lumínica, ciclos de luz/oscuridad, concentración de nutrientes, pH, especies reactivas de oxígeno, sales y presencia de inhibidores de procesos metabólicos a diferente nivel. Es importante resaltar que esta microalga es de difícil cultivo; así como en la obtención del pigmento en cantidades de interés, debido a su ciclo celular complejo. De igual forma, un mayor entendimiento de las bases moleculares de la relación -condiciones de estrés-inducción- acumulación de astaxantina en H. pluvialis, podría ser útil para aumentar la productividad de astaxantina.

Microalgae are a source of a large number of bioactive compounds of industrial importance, such as carotenoids used as natural colorants in food and feed, as well as in pharmaceuticals, cosmetics and aquaculture. They also have been studied as effective compounds for the prevention of different diseases due to their antioxidant, immunoregulatory, anti-inflammatory and anticarcinogenic properties. In biotechnology applications astaxanthin is the most important ketocarotenoide. Currently most astaxanthin is produced by chemical synthesis and sold at U.S. $ 2500/kg. The high price and increasing demand of this compound in different industries, especially of natural origin creates an interest in the astaxanthin production from microalgae as Haematococcus pluvialis that accumulate significant amounts (more than 4%/g dry weight) and better quality what is obtained from sources such as yeast and plants. The pigment accumulation in H. pluvialis occurs during the transformation of microalgae from the vegetative state (green phase) to aplanospora (red phase) when growth ends in the stationary phase. The types of stress that induce astaxanthin accumulation are temperature, light intensity, cycles of light / dark, nutrient concentration, pH, reactive oxygen species, salts and presence of metabolic processes inhibitors at different levels. Is important to take in account that this microalgae is hard to grow and obtain the pigment in amounts of interest could be complicated due to complex cell cycle. Similarly, a better understanding of the molecular basis of the relationship, stress-inducing conditions, astaxanthin accumulation in H. pluvialis, might be helpful for increasing productivity of astaxanthin.

Xanthophyllomyces dendrorhous (Phaffia rhodozyma) on stromata of Cyttaria hariotii in northwestern Patagonian Nothofagus forests

The occurrence and distribution of Xanthophyllomyces dendrorhous associated with Cyttaria hariotii parasitizing three Nothofagus species (N. dombeyi, N. antarctica and N. pumilio) in northwestern Patagonia (Argentina), as well as the factors that may affect this distribution were herein studied. Between 2000 and 2007, samples were obtained from 18 different locations. Based on physiological tests and morphological characteristics of sexual structures, 72 isolates were identified as X. dendrorhous. Representative strains were studied by MSP-PCR fingerprinting and sequence analysis of the ITS region. MSP-PCR fingerprints were similar for the newly isolated strains, and were also identical to the profiles of the strains previously found in this region. Patagonian strains appear to be a genetically uniform and distinct population, supporting the hypothesis that the association with different host species has determined genetically distinct X. dendrorhous populations worldwide. X. dendrorhous was recovered from N. dombeyi and N. antarctica. Approximately half the sampling sites and samples were positive for X. dendrorhous, but the isolation recovery rate was low. X. dendrorhous was absent in the early stages of ascostromata maturation, becoming more abundant in later stages. The present work represents a step forward in the understanding of the natural distribution and ecology of this biotechnologically relevant yeast.

Xanthophyllomyces dendrorhous (Phaffia rhodozyma) asociado a estromas de Cyttaria hariotii en bosques de Nothofagus en el noroeste de la Patagonia. Se estudió la ocurrencia y la distribución de Xanthophyllomyces dendrorhous asociado a Cyttaria hariotii en tres especies de Nothofagus (N. dombeyi, N. antarctica y N. pumilio) del noroeste de la Patagonia (Argentina), y los factores que podrían afectar esta distribución. El muestreo se realizó entre 2000 y 2007 en 18 sitios diferentes. Según las pruebas fisiológicas y las características morfológicas de las estructuras sexuales, 72 de los aislamientos obtenidos se identificaron como X. dendrorhous. Se estudiaron cepas representativas mediante la técnica de MSP-PCR fingerprinting y secuenciación de la región ITS. Los perfiles de MSP-PCR fueron similares, tanto entre los nuevos aislamientos como entre estos y los de cepas previamente obtenidas en la región. Aparentemente, las cepas patagónicas forman una población genéticamente uniforme y distinta de otras poblaciones. Esto apoya la hipótesis de que la asociación con diferentes especies hospedadoras ha determinado la diferenciación genética de X. dendrorhous en todo el mundo. X. dendrorhous se recuperó de N. dombeyi y de N. antarctica. Aproximadamente la mitad de los sitios de muestreo y de muestras fueron positivos para X. dendrorhous, pero la tasa de aislamiento fue muy baja. X. dendrorhous está ausente en estadios tempranos de maduración de ascostromas y se hace más abundante en estadios más tardíos. El presente trabajo contribuye al mejor entendimiento de la distribución natural y la ecología de esta levadura, de relevancia biotecnológica.

Astaxanthin: structural and functional aspects / Astaxantina: aspectos estruturais e funcionais

Astaxanthin, a carotenoid belonging to the xanthophyll class, has stirred great interest due to its antioxidant capacity and its possible role in reducing the risk of some diseases. Astaxanthin occurs naturally in microalgae, such as Haematococcus pluvialis and the yeast Phaffia rhodozyma, and has also been considered to be the major carotenoid in salmon and crustaceans. Shrimp processing waste, which is generally discarded, is also an important source of astaxanthin. The antioxidant activity of astaxanthin has been observed to modulate biological functions related to lipid peroxidation, having beneficial effects on chronic diseases such as cardiovascular disease, macular degeneration and cancer. Researches have shown that both astaxanthin obtained from natural sources and its synthetic counterpart produce satisfactory effects, but studies in humans are limited to natural sources. There is no established nutritional recommendation regarding astaxanthin daily intake but most studies reported beneficial results from a daily intake of 4mg. Thus, this review discusses some aspects of the carotenoid astaxanthin, highlighting its chemical structure and antioxidant activity, and some studies that report its use in humans.

A astaxantina, carotenóide pertencente à classe das xantofilas, tem despertado grande interesse devido à sua capacidade antioxidante e possível papel na redução de risco de algumas doenças. A astaxantina pode ser encontrada naturalmente em microalgas como Haematococcus pluvialis e na levedura Phaffia rhodozyma como também tem sido considerada principal carotenóide em salmão e crustáceos. Os resíduos do processamento de camarão, geralmente descartados, são também importante fonte de astaxantina. A atividade antioxidante da astaxantina tem demonstrado importante função na modulação de funções biológicas relacionadas à peroxidação lipídica, desempenhando efeitos benéficos em doenças crônicas como doenças cardiovasculares, degeneração macular e câncer. Pesquisas têm demonstrado efeitos satisfatórios da astaxantina obtida de fontes naturais assim como da obtida sinteticamente, porém os estudos em humanos se limitam à utilização de fontes naturais. Não há recomendação nutricional estabelecida para a ingestão diária de 4mg de astaxantina, mas muitos estudos relatam resultados benéficos com a ingestão diária média de 4mg. Assim, a presente revisão discute alguns aspectos do carotenóide astaxantina, com destaque para sua estrutura química e atividade antioxidante, mostrando também alguns estudos que relatam seu uso em humanos.

Sexual stages of the female portion in the scallop Nodipecten nodosus (Linné, 1758) and astaxanthin quantity in each stage / Estágios sexuais da porção feminina da gônada da vieira Nodipecten nodosus (Linné, 1758) e a quantidade de astaxantina em cada estágio

This work describes the gametogenic cycle of the scallop Nodipecten nodosus kept in a culture system. To this end, during one year, samples were taken from the broodstocks every 30 days to be submitted to macroscopic and microscopic analyses and to measure the amount of astaxanthin. To perform the microscopic evaluation, 5 μ slices from the median portion of the female part of the gonad were submitted to the pattern methodology for histological analyses with paraffin and HE coloration. The remaining portion of the female gonad was lyophilised to extract and quantify the levels of astaxanthin using HPLC. The microscopic analyses revealed four well defined stages for the reproductive cycle. Analyses of data taken throughout the year indicated preferential spawning periods from December to January and from July to September. The astaxanthin analyses showed higher amounts of this carotenoid during the advanced pre-spawning and the initial spawning periods than during gametogenesis, initial pre-spawning, advanced spawning, and the spent stages. According to these results, it was possible to establish a descriptive table of the sexual stages of the female portion of the gonad and the amount of astaxanthin in the sexual stage of the scallop Nodipecten nodosus.

Este trabalho descreve o ciclo gametogênico da vieira Nodipecten nodosus mantida em ambiente de cultivo. Para isto, durante um ano, amostras de indivíduos reprodutores foram coletadas a cada 30 dias e submetidas à avaliação macroscópica e microscópica e à quantificação de astaxantina. Para a avaliação microscópica, secções de 5 μ da porção mediana feminina da gônada foram submetidas à metodologia de análise histológica padrão em parafina e coloração HE. O restante da porção feminina da gônada foi liofilizado para extração e quantificação de astaxantina em HPLC. A avaliação microscópica permitiu a descrição de quatro estágios bem definidos para o ciclo reprodutivo. Na análise ao longo do ano, foram observados períodos preferenciais de desova em dezembro e janeiro e de julho a setembro. A análise da quantidade de astaxantina, mostrou, nos estádios de pré-desova avançada e de desova inicial, uma maior quantidade desse carotenoide em comparação aos estádios de gametogênese, pré-desova inicial, desova avançada e repouso. Em função desses resultados, foi possível estabelecer um quadro descritivo dos estágios sexuais da porção feminina da gônada e quantidade de astaxantina em cada estágio sexual da vieira Nodipecten nodosus.