Evaluación de una nueva formulación de compuestos naturales sobre la modificación de los componentes del síndrome metabólico en adultos con sobrepeso

El sobrepeso y la obesidad, condiciones cada vez más frecuentes en Chile y el Mundo, se definen como una enfermedad crónica caracterizada por la acumulación excesiva de grasa corporal que puede ser perjudicial para la salud. El exceso de grasa corporal es el principal factor patogénico para el desarrollo de resistencia a la insulina y síndrome metabólico (SM), este último caracterizado por la agrupación de una serie de anormalidades metabólicas que determinan un mayor riesgo de padecer enfermedades metabólicas y mortalidad cardiovascular. El objetivo de este estudio piloto transversal y observacional fue evaluar una nueva formulación de compuestos naturales, Delphinol®, resveratrol y ácido oleanólico, frente a parámetros asociados al SM en una población joven con exceso de peso, al ingerir durante 22 semanas la nueva formulación. La evaluación fue realizada en base al estado clínico y antropométrico de 20 sujetos voluntarios (ambos sexos, 18 a 30 años e IMC 26 a 42), mediante valoración médica y exámenes de laboratorio clínico para cada componente del SM (obesidad abdominal, triglicéridos, HDL, presión arterial y glicemia en ayunas). De esta manera, se observó que con la ingesta diaria de esta formulación existe una reducción significativa de los niveles de glicemia, índice HOMA-IR, triglicéridos y aumento de HDL-colesterol. Estos resultados preliminares se traducirían en un beneficio sobre el estado de salud de los individuos con sobrepeso y obesidad, lo cual impactaría en reducir los índices de SM y de esta manera enlentecer la progresión hacia enfermedades crónicas como diabetes y dislipidemia, y contribuir también a disminuir el riesgo cardiometabólico asociado.

Overweight and obesity, increasingly frequent conditions in Chile and the world, are defined as chronic diseases characterized by the excessive accumulation of body fat, that can be detrimental to health. Excess body fat is the main pathogenic factor for the development of insulin resistance and metabolic syndrome, the latter characterized by a cluster of metabolic abnormalities that increase risk of metabolic diseases and cardiovascular mortality. The objective of this preliminary cross-sectional, observational study was to evaluate a new formulation of natural compounds, Delphinol®, resveratrol and oleanolic acid, against metabolic syndrome components in a young population with excess weight, through the intake during 22 weeks of the new formulation. The evaluation was carried out based on the clinical and anthropometric status of 20 volunteer subjects (both gender, 18 to 30 years and BMI 26 to 42), medical evaluation and laboratory tests using each metabolic syndrome component (abdominal obesity, triglycerides, HDL, blood pressure y fasting glicaemia). It was observed that with the daily intake of this formulation there was a significant reduction in blood glucose levels, HOMA-IR index, triglycerides and an increase in HDL-cholesterol. These preliminary results would translate into a benefit in the health status of overweight and obese individuals, which would impact on reducing rates of metabolic syndrome. Thus, slowing down the progression of chronic diseases such as diabetes and dyslipidemia, and also contributing to decreasing the associated cardiometabolic risk.

Determination of the content of ursolic and oleanolic acid in the cuticular wax of fruits of different species of Rosaceae / Determinación del contenido de ácido ursólico y oleanólico en la cera cuticular de frutos de diferentes especies de Rosaceae / Determinação do teor de ácido ursólico e oleanólico na cera cuticular de frutos de diferentes espécies de Rosaceae

Abstract Ursolic acid (UA) and oleanolic acid (OA) are two widely distributed triterpenes in fruits, especially those belonging to Rosaceae family. These triterpene isomers are of great pharmacological interest due to their multiple bioactive properties. For this reason, the objective of this study was to determine the content of UA and OA extracted from the cuticular wax of five highly edible fruits (quince, loquat, pear, peach and apple) all belonging to the Rosaceae family. The acids were analyzed by high performance liquid chromatography. Both UA and OA are present in all these fruits, however, UA is in greater quantities.

Resumen El ácido ursólico y el ácido oleanólico (AO) son dos triterpenos ampliamente distribuidos en los frutos, sobre todo en aquellos que pertenecen a la familia Rosaceae. Estos isómeros triterpénicos son de gran interés farmacológico por sus múltiples propiedades bioactivas. Por esta razón, el presente trabajo tuvo como objetivo determinar el contenido de AU y AO extraídos de la cera cuticular de cinco frutos bastante comestibles (membrillo, níspero, pera, durazno y manzana), todos ellos pertenecientes a la familia Rosaceae. El método empleado para analizar estos ácidos fue cromatografía líquida de alta eficiencia. De lo anterior, se concluyó que tanto el AU como el AO están presentes en todos los frutos mencionados, sin embargo, el AU se encuentra en mayores cantidades.

Resumo Ácido ursólico e ácido oleanólico (AO) são dois triterpenos amplamente distribuídos em frutos, especialmente aqueles pertencentes à família Rosaceae, estes isómeros triterpénicos são de grande interesse farmacológico por suas múltiplas propriedades bioativas. Por esse motivo, o objetivo deste estudo foi determinar o conteúdo de AU e AO extraídos da cera cuticular de cinco frutos altamente comestíveis (marmelo, néspera, péra, pêssego e maçã) pertencentes à família Rosaceae. O método utilizado para esse fim foi a cromatografia líquida de alta eficiência. O resultado mostrou que AU e AO estão presentes em todas essas frutas, sendo a primeira a que está em maior quantidade.

Identificación de metabolitos secundarios de Anredera vesicaria (Yuca hiedra) / Identification of secondary metabolites from Anredera vesicaria (Yuca Hiedra)

INTRODUCCIÓN: Anredera vesicaria es una planta muy empleada en la región oriental de Cuba para tratar inflamaciones provocadas por golpes y fracturas, sin embargo, no existen datos de su composición química que justifiquen su uso como antiinflamatorio. OBJETIVO: identificar metabolitos secundarios de interés medicinal en las hojas, tallos y rizomas de Anredera vesicaria. MÉTODOS: a la biomasa recolectada se le aplicó un proceso de lavado, desinfección, secado y pulverización. Un ejemplar fue identificado y consignado en la serie Catasús, número 2601. Muestras aéreas y subterráneas se sometieron a extracciones con agua y etanol usándose ultrasonido. A los extractos se les realizó tamizaje fitoquímico, cuyos resultados fueron corroborados por cromatografía de capa delgada y espectroscopía ultravioleta e infrarroja. RESULTADOS: se identificaron carbohidratos, fenoles, flavonoides, cumarinas, alcaloides, triterpenos, mucílagos y saponinas. En el extracto etanólico de las hojas se encontró la mayor diversidad de metabolitos secundarios, sin embargo, en los rizomas hay mayor abundancia de fenoles, esteroides y mucílagos. A partir de los rizomas se aisló un sólido blanco amorfo que fue identificado como ácido oleanólico. CONCLUSIONES: la abundancia de triterpenos y mucílagos en Anredera vesicaria podría contribuir con su actividad antiiflamatoria.

INTRODUCTION: Anredera vesicaria is a plant very used in the East of Cuba to treat inflammations provoked by blows and fractures, however, data of the chemical composition that justify its use as antiinflamatory don't exist. OBJECTIVE: To Identify secondary metabolites with medicinal interest in the sheets, stems and rhizomes from Anredera vesicaria. METHODS: To the recollected biomass was applied a process of washing, disinfection, drying and pulverization. A sample was identified and consigned in the Catasús series, with number 2601. Aerial and subterranean samples submitted extractions with water and ethanol themselves using ultrasound. To the extracts were carried out the phytochemical screening whose results were corroborated by thin layer chromatography and ultraviolet and infrared spectroscopy. RESULTS: Carbohydrates, phenols, flavonoids, coumarins, alkaloids, triterpenes, mucilages and saponines were identified. In the ethanolic extract from leaves it was found the biggest diversity of secondary metabolites, however, in the rhizomes there are bigger abundance of phenols, steroids and mucilages. Starting from rhizomes was isolate an amorphous white solid which was identified as oleanolic acid. CONCLUSIONS: The abundance of triterpenes and mucilages in Anredera vesicaria could to contribute with their anti-inflamatory activity.

Acute and subacute toxicity (28 days) of a mixture of ursolic acid and oleanolic acid obtained from Bouvardia ternifolia in mice / Toxicidad aguda y subaguda (28 días) en ratones, de la mezcla de ácido ursólico y ácido oleanólico obtenida de Bouvardia ternifolia

Ursolic acid (UA) and oleanolic acid (OA) are triterpenes that are found in a large number of medicinal plants, one of which is the species Bouvardia ternifolia. These compounds have been shown to have around 120 types of biological activity, especially the hepatoprotective, anti-inflammatory and antimycobacterial effects. Despite having a high therapeutic potential, not much information concerning their toxicity is available. This article describes the results of acute and subacute (28 days) toxicity evaluations in Balb/c mice (both sexes) treated with the mixture of UA/OA obtained from B. ternifolia at doses of 6.5 and 13 mg/kg. The LD50 was >300 mg/kg. During the subacute administration, there was no death of animals and no changes were observed in the growth or weight of the different organs when compared to the control groups. Studies of blood chemistry and blood count showed normal levels in all parameters evaluated. The histopathology of major organs showed no changes or abnormalities. The mixture UA/OA is indeed safe when administered subcutaneously as a single dose of 300 mg/kg or in repeated doses of 13 mg/kg during 28 days.

Los ácidos ursólico (UA) y oleanólico (OA) son triterpenos que se encuentran distribuidos en un gran número de plantas medicinales, una de ellas es la especie Bouvardia ternifolia. Estos compuestos han mostrado alrededor de 120 actividades biológicas, destacando los efectos hepatoprotector, antiinflamatorio y antimicobacteriano. A pesar de ser compuestos con un alto potencial terapéutico, no se han documentado muchos datos acerca de su toxicidad. En este artículo se describen los resultados de la evaluación de toxicidad aguda y subaguda (28 días) en ratones Balb/c de ambos sexos, tratados con la mezcla de AU/AO obtenida de B. ternifolia a dosis de 6.5 y 13 mg/kg. La DL50 fue > 300 mg/kg. Durante la administración subaguda, no hubo muerte de animales, tampoco se observaron alteraciones en su crecimiento ni alteraciones en el peso de los diferentes órganos. Los estudios de biometría hemática y química sanguínea mostraron niveles normales en todos los parámetros evaluados. Los análisis histopatológicos de los principales órganos no presentaron cambios o anormalidades. La mezcla UA/OA es prácticamente inocua cuando se administra subcutáneamente en dosis única de 300 mg/kg y 13 mg/kg en dosis repetida (28 días).

Secondary metabolites isolated from Richardia brasiliensis Gomes (Rubiaceae) / Metabólitos secundários isolados de Richardia brasiliensis Gomes (Rubiaceae)

A família Rubiaceae compreende cerca de 637 gêneros e aproximadamente 10700 espécies, ocorrendo essencialmente nas regiões tropicais do Brasil. Richardia brasiliensis Gomes, popularmente conhecida por "poaia branca", é uma planta nativa da região sul do Brasil, utilizada na medicina popular como anti-emética e no tratamento de diabetes. Este trabalho reporta o isolamento e identificação estrutural de um flavonóide glicosilado, um triterpeno, uma cumarina e dois derivados de ácido benzóico, objetivando contribuir para quimiotaxonomia do gênero Richardia. Através deste estudo foi possível isolar e identificar os metabólitos isorametina-3-O-rutinosídeo, ácido oleanólico, a cumarina escopoletina e os ácidos p-hidroxi-benzóico e m-metoxi-p-hidroxi-benzóico, todos isolados pela primeira vez no gênero, exceto o último, apresentando, portanto, relevante importância quimiotaxonômica para o mesmo. As estruturas foram identificadas com o uso de técnicas espectroscópicas de IV, RMN ¹H e 13C uni e bidimensionais e comparação com dados da literatura.

The family Rubiaceae comprises around 637 genera and approximately 10,700 species, occurring essentially in tropical regions of Brazil. Richardia brasiliensis Gomes, known popularly as "poaia branca", is native to Brazil south region, used in folk medicine as anti-emetic and in the treatment of diabetes. This work reports the isolation and structural identification of a flavonoid glycoside, a triterpene, a coumarin and two benzoic acid derivatives, aiming at contributing to the chemotaxonomy of the genus Richardia, through a phytochemical study of Richardia brasiliensis. By means of this study the metabolites isorhamnetin-3-O-rutinoside, oleanolic acid, the coumarin scopoletin and p-hydroxy-benzoic and m-methoxy-p-hydroxy-benzoic acids were isolated and identified. All of them, but the latter, were isolated for the first time in the genus, thereby presenting relevant chemotaxonomic importance to it. The structures were identified using spectroscopic techniques such as IR, one and two-dimensional ¹H and 13C NMR besides comparison with literature data.

Ecdisterona de Pfaffia tuberosa (Spreng. ) Hicken / Ecdysterone from Pfaffia tuberosa (Spreng. ) Hicken

As raízes secas da espécie brasileira Pfaffia tuberosa (Spreng.) Hicken foram submetidas a extração com metanol. Deste extrato metanólico foram isolados a ecdisterona e o ácido oleanólico, através de processos de separação por HPLC e cromatografia em coluna. Tanto a ecdisterona como o ácido oleanólico foram identificados comparativamenve com os respec­tivos padrões. Análise quantitativa por HPLC mostrou 0,23 por cento de ecdisterona. Este teor foi considerado baixo em relação a outra espécie, também brasileira, a Pfaffia iresinoides.

In this paper, we wish to report the isolation and identification of ecdysterone from Pfaffia tuberosa (Spreng.) Hicken. The roots of Pfaffia tuberosa (Spreng.) Hicken were colected in the Mato Grosso State - Brazil. The dried and sliced roots (197g) were extracted with hot MeOH. A suspension of the resulting MeOH extract in the water was treated with n-BuOH. The n-BuOH layer was concentrated in vacuo to give a brown viscous oil (5g), wich was chromatographed on silicagel (65g) using CHCl3 - MeOH - H2O (80:20:10) lower phase, and 15ml fractions were collected. Fractions 11-13 were concentrated and the residual solid was recrystallized from EtOH to afford oleanolic acid (65mg). The crystalline residue obtained from fractions 44-56 was recrystallized from EtOAC-MeOH to give ecdysterone (87mg). Each compound was identified by direct comparison with an authentic sample. Further HPLC quantitative analysis showed lower content of ecdysterone (0,23 percent) compared with that of Pfaffia iresinoides Spreng.