Cellular target of isoquercetin from Passiflora ligularis Juss for glucose uptake in rat soleus muscle.

Quercetin 3-O-beta-d-glucopyranoside (isoquercetin) is one of the most frequent metabolites of the Passiflora ligularis Juss. The purpose of this study was to investigate the effect of the aqueous extract and ethanol fraction from P. ligularis Juss leaves on glycaemia and the mechanism of action of isoquercetin on glucose uptake. In the glucose tolerance test, the aqueous extract and ethanol fraction from P. ligularis Juss (125 mg/kg to 500 mg/kg o. g.) reduced glycaemia and increased the hepatic and muscular glycogen content. Phytochemical analysis evidenced the dominant presence of isoquercetin in the extract and fraction from leaves of P. ligularis Juss. Isoquercetin mediates the stimulatory effect on glucose uptake independent of insulin receptor activation but, involve PI3K, MAPK, MEK/ERK pathways and de novo protein synthesis to GLUT-4 translocation. Overall findings revealed that isoquercetin and aqueous extract and ethanol fraction of P. ligularis Juss leaves might be a promising functional food or medicine for the treatment or prevention of diabetes.

Astragalin augments basal calcium influx and insulin secretion in rat pancreatic islets.

Astragalin is a flavonol glycoside with several biological activities, including antidiabetic properties. The objective of this study was to investigate the effects of astragalin on glycaemia and insulin secretion, in vivo, and on calcium influx and insulin secretion in isolated rat pancreatic islets, ex vivo. Astragalin (1 and 10 mg / kg) was administered by oral gavage to fasted Wistar rats and serum glucose and plasma insulin were measured. Isolated pancreatic islets were used to measure basal insulin secretion and calcium influx. Astragalin (10 mg/ kg) decreased glycaemia and increased insulin secretion significantly at 15-180 min, respectively, in the glucose tolerance test. In isolated pancreatic cells, astragalin (100 µM) stimulated calcium influx through a mechanism involving ATP-dependent potassium channels, L-type voltage-dependent calcium channels, the sarcoendoplasmic reticulum calcium transport ATPase (SERCA), PKC and PKA. These findings highlight the dietary coadjuvant, astragalin, as a potential insulin secretagogue that may contribute to glucose homeostasis.

In vitro intestinal permeability studies, pharmacokinetics and tissue distribution of 6-methylcoumarin after oral and intraperitoneal administration in Wistar rats

ABSTRACT 6-Methylcoumarin (6MC) is a semisynthetic coumarin with important in vitro and in vivo anti-inflammatory activity. In order to continue the pre-clinical characterization of this molecule, in vitro intestinal permeability, plasma profile and tissue distribution after oral administration in rats were studied. The permeability of 6MC was evaluated by the Caco-2 cellular model in both the apical-basal (A-B) and basal-apical (B-A) directions. The pharmacokinetics and biodistribution were evaluated in rats after oral and intraperitoneal administration at doses of 200 mg/kg. Transport experiments with Caco-2 cells showed that 6MC presented high permeability at all concentrations evaluated. This finding suggested that 6MC could be transported across the gut wall by passive diffusion. The plasma concentration-time curve showed that the maximum concentration (Cmax) was 17.13 ± 2.90 µg/mL at maximum time (Tmax) of 30 min for the oral route and Cmax 26.18 ± 2.47 µg/mL at 6.0 min for the intraperitoneal administration, with elimination constant of (Ke ) 0.0070 min-1 and a short life half time of (T1/2 ) lower that 120 min. The distribution study showed that 6MC has high accumulation in the liver, and widespread distribution in all the organs evaluated.

Inhibitory effects of an extract of fruits of Physalis peruviana on some intestinal carbohydrases / Evaluación in vitro del efecto de un extracto de frutos de Physalis peruviana sobre algunas carbohidrasas intestinales

Physalis peruviana is an Andean specie whose fruits are eaten as food and also has been reported in Colombian folk medicine for diabetes mellitus treatment. In addition, previous pharmacological studies on diabetic Wistar rats, an extract of P. peruviana fruits has been showed antidiabetic activity. In order to deepen in P. peruviana action mode as antidiabetic, in this investigation were determinate the Inhibitory Concentrations 50 (IC50) of P. peruviana fruits crude extract on alpha glucosidase from S. cerevisiae and from intestinal rat powder, on maltase and alpha amylase enzymes. The kinetic behavior of the extract on each enzyme was also investigated, and the enzyme constant (Km) and maximum rate (Vmax) were determined. Extract of fruits of P. peruviana showed different IC50 for alpha glucosidase from S. cerevisiae and intestinal rat powder, suggesting greater affinity for the enzyme of mammalian source (4114.7 and 3552.7 µg/mL, respectively). For maltase, the IC50 was close to that obtained for alpha glucosidase (4191.0 µg/mL) while for alpha amylase, the extract exhibited the highest inhibition (IC50: 619.9 g/mL). Regarding kinetic behavior, the extract showed competitive inhibition on alpha-glucosidase and maltase, and on the non-competitive type of alpha amylase. These suggest that inhibition of intestinal carbohydrases is one of the modes of action for the antidiabetic activity of fruits of P. peruviana.

Physalis peruviana es una especie andina, cuyos frutos además de ser usados como alimento, son empleados en la medicina tradicional para el tratamiento de la diabetes mellitus. Además, estudios farmacológicos previos en ratas Wistar han demostrado actividad antidiabética de extractos de frutos de P. peruviana. Con el fin de profundizar en el modo de acción de la actividad antidiabética de los frutos de P. peruviana, en la presente investigación se determinó la concentración inhibitoria 50 (CI50) del extracto crudo de frutos de P. peruviana, sobre las enzimas alfa glucosidasa obtenida de S. cerevisiae y de polvo intestinal de rata, maltasa y alfa amilasa. El comportamiento cinético del extracto sobre cada una de las enzimas también fue investigado y la constante enzimática (Km) y la velocidad máxima (Vmax) fueron determinadas. El extracto de frutos de P. peruviana, mostró diferentes valores de CI50 para alfa glucosidasa obtenida de S. cerevisiae y para la obtenida de polvo intestinal de rata, sugiriendo una mayor afinidad por la enzima de origen mamífero (4114,7 and 3552,7 µg/mL, respectivamente). Para maltasa la CI50 fue cercana a la obtenida para alfa glucosidasa (4191,0 µg/mL), mientras para alfa amilasa, el extracto presentó la mayor inhibición (CI50: 619,9 g/mL). Respecto al comportamiento cinético, el extracto mostró inhibición de tipo competitiva sobre alfa glucosidasa y maltasa y no competitiva sobre alfa amilasa. Los resultados sugieren que la inhibición de carbohidrasas intestinales es uno de los modos de acción de los frutos de P. peruviana como agente antidiabético.

Biodistribution study of free and microencapsulated 6-methylcoumarin in Wistar rats by HPLC.

A sensitive, specific and reproducible HPLC method has been developed and validated for the quantitative determination of 6-methylcoumarin (6MC) in plasma and other tissues in Wistar rats. A C18 column was used with UV detection at 321 nm and a gradient system consisting of methanol-deionized water was used as mobile phase. The retention time for 6MC was 14.921 min and no interfering peaks were observed for any of the matrices. Linear relationships (r(2) > 0.997) were obtained between the peak height ratios and the corresponding biological sample concentrations over the range 0.4-12.8 µg/mL. Precision and accuracy were evaluated; the coefficient of variation and the relative error for all of the organs were <2 and 7%, respectively. The limit of quantitation was 0.20 µg/mL for the heart and 0.30 µg/mL for the other tissues evaluated. This HPLC method was successfully used in the determination of 6MC in the biodistribution study after administration of 200 mg/kg of both 6MC-free and 6MC-loaded polymeric microparticles. In this study, extensive 6MC was found, in both free and microencapsulated forms, in all the organs tested. The 6MC-free showed a range of between 1.7 and 11.5 µg/g, while the microencapsulated 6MC showed concentrations of between 6.35 and 17.7 µg/g, suggesting that 6MC improved absorption rate.

Caracterización del avance teórico, investigativo y/o de intervención en resiliencia desde el ámbito de las universidades en Colombia / Characterization of the research, the intervention and the theoretical advances in resiliency in the universities in Colombia

Este artículo presenta los resultados de la investigación realizada con el fin de caracterizar los avances teóricos, investigativos y/o de intervención en resiliencia desde el ámbito de las universidades en Colombia. Para conseguir este objetivo se analizaron 74 documentos procedentes de 14 universidades colombianas. El abordaje realizado permitió describir las investigaciones, reflexiones e intervenciones realizadas en las universidades colombianas, considerando dos categorías: a) identificación de documentos y b) análisis de contenido. Se realizó un análisis descriptivo y posteriormente interpretativo, a partir de los cuales se llegó a conclusiones y propuestas particulares para cada categoría y generales en torno a la resiliencia. Una novedad de las investigaciones estudiadas reside en las problemáticas abordadas.

This article presents the results of the research carried out in order to characterize research, the intervention and the theoretical advances in resiliency in the universities in Colombia. With the aim to achieve this objective were analyzed 74 documents from 14 Colombian universities. This research allowed describe the investigations, reflections and interventions the Colombian universities in resiliency taking in to account the following categories: a. identification of documents. b. content analysis. These categories were used for a descriptive and interpretive analysis the documents and achieving individual and general conclusions on resiliency. A novelty of this research study was the studies issues.

Efecto de algunas especies vegetales antiinflamatorias sobre la actividad enzimática de elastasa y mieloperoxidasa / Effect of some antiinflammatory plant species on elastase and myeloperoxidase enzyme activity

Se evaluó el efecto de extractos metanólicos y acuosos de las especies vegetales Critoniella acuminata, Salvia rubescens, Phenax rugosus (Poir.) Wedd y Tabebuia chrysanta G. Nicholson sobre las enzimas elastasa y mieloperoxidasa, relacionadas con el proceso de desgranulación leucocitaria, y se determinó el potencial efecto inhibitorio directo sobre la enzima o la inhibición de la desgranulación de los neutrófilos polimorfonucleares. Los extractos de Critoniella acuminata y Salvia rubescens presentaron efectos sobre el proceso de desgranulación y la actividad de las enzimas mieloperoxidasa y elastasa; en el caso de los extractos de Phenax rugosus, estos no mostraron un efecto significativo sobre ninguna de las enzimas. De la especie Tabebuia chrysanta solamente el extracto metanólico mostró efecto sobre la inhibición de la actividad elastasa.

In this work, the effect of aqueous and methanolic extracts of the plants species Critoniella acuminata, Salvia rubescens, Phenax rugosus (Poir.) Wedd and Tabebuia chrysanta G. on the enzymes elastase and myeloperoxidase, involved in degranulation leukocyte process, was evaluated, identifying the potential direct inhibitory effect on the enzyme and/or inhibition of the desgranulation of polymorphonuclear neutrophils. Extracts of Critoniella acuminata and Salvia rubescens presented effects on the degranulation process and the inhibition of the enzyme elastase and myeloperoxidase; the extracts of Phenax rugosus do not showed significant effect. Tabebuia chrysanta methanolic extract only showed effect on inhibition of elastase activity.

In vitro studies on the relationship between the anti-inflammatory activity of Physalis peruviana extracts and the phagocytic process.

The study of plants used in traditional medicine has drawn the attention of researchers as an alternative in the development of new therapeutics agents, such as the American Solanaceae Physalis peruviana, which has significant anti-inflammatory activity. The Physalis peruviana anti-inflammatory effect of ethanol or ether calyces extracts on the phagocytic process was assessed by using an in vitro phagocytosis model (Leishmania panamensis infection to murine macrophages). The Physalis peruviana extracts do not inhibit microorganism internalization and have no parasiticide effect. Most ET and EP extracts negatively affected the parasite's invasion of macrophages (Infected cells increased.). This observation might result from a down-regulation of the macrophage's microbicide ability associated with a selective reduction of proinflammatory cytokines levels. Physalis peruviana's anti-inflammatory activity described in this model is related to an immunomodulatory effect exerted on macrophages infected, which directly or indirectly "blocks" their ability to secrete soluble proinflammatory mediators.

Efecto antinociceptivo de Critoniella acuminata, Physalis peruviana y Salvia rubescens / Antinociceptive effect of Critoniella acuminata, Physalis peruviana and Salvia rubescens

Se evaluó el efecto antinociceptivo de extractos, fracciones y compuestos de Critoniella acuminata, Physalis peruviana y Salvia rubescens mediante los métodos de placa caliente, contorsiones abdominales inducidas por ácido acético y ensayo de la formalina. La fracción de Critoniella acuminata en dosis de 100 mg/kg p.o. presentó actividad antinociceptiva al aumentar el tiempo de reacción del animal ante la aplicación de un estímulo térmico (método de la placa caliente), mientras que la fracción de Physalis peruviana, en una dosis de 100 mg/kg p. o., ejerce un efecto antinociceptivo frente al dolor generado por estímulos químicos (dolor visceral agudo) al inhibir en un 40 por ciento las contorsiones abdominales inducidas por ácido acético y el número de lamidos durante la fase ii (dolor inflamatorio agudo) en el ensayo de formalina. Estos resultados sugieren que la ayapina y la fracción de Physalis peruviana estudiadas tienen actividad antinociceptiva, con posibles mecanismos de tipo opioide y aine, respectivamente.

The antinociceptive effect of extracts, fractions and compounds of Critoniella acuminata, Physalis peruviana and Salvia rubescens were evaluated by the follow methods: Hot Plate test, acetic acid induced abdominal writhing and Formalin test. The fraction of Critoniella acuminata at doses of 100mg/kg p.o. exhibited antinociceptive effect in the hot plate test; while Physalis peruviana fraction at doses of 100 mg/kg p.o., showed an antinociceptive effect against the pain chemically induced. This fraction produced 40 percent inhibition of the acetic acid induced writhing (acute visceral nociception) and the licks during phase ii (acute inflammatory nociception)of the formalin test. The findings of this experimental study suggest that fractions of Critoniella acuminata and Physalis peruviana possess antinociceptive activity with opioid and nsaid-like mechanisms respectively.

Anti-inflammatory effects of the gorgonian Pseudopterogorgia elisabethae collected at the Islands of Providencia and San Andrés (SW Caribbean).

BACKGROUND: We are reporting for the first time the in vivo anti-inflammatory activity of extracts and fractions, and in vitro anti-inflammatory activity of pure compounds, all isolated from Pseudopterogorgia elisabethae collected at the Providencia (chemotype 1) and San Andrés (chemotype 2) Islands (SW Caribbean). METHODS: Extracts from P. elisabethae were fractionated on silica gel to yield fractions: F-1 (pseudopterosins PsQ, PsS and PsU) and F-2 (amphilectosins A and B, PsG, PsK, PsP and PsT and seco-pseudopterosins seco-PsJ and seco-PsK) from chemotype 1, and F-3 (elisabethatrienol, 10-acetoxy-9-hydroxy- and 9-acetoxy-10-hydroxy-amphilecta-8,10,12,14-tetraenes (interconverting mixture) and amphilecta-8(13),11,14-triene-9,10-dione) from chemotype 2. By using preparative RP-HPLC and spectroscopic means, we obtained the pure PsG, PsK, PsP, PsQ, PsS, PsT, PsU, seco-PsK and the interconverting mixture of non-glycosylated diterpenes (IMNGD). The anti-inflammatory properties of extracts and fractions were evaluated using in vivo model "12-O-tetradecanoyl-phorbol-acetate (TPA)-induced mouse ear oedema". The activities of pure compounds and of the IMNGD were evaluated using in vitro assays myeloperoxidase (MPO) release (by human polymorphonuclear neutrophils (PMNs)), nitric oxide release (by J-774 cells) and scavenger activity on NO. RESULTS: In the in vivo anti-inflammatory assay, extracts and F-3 showed low inhibition levels of inflammation compared to indomethacin, F-1 and F-2. Additionally, we evaluated the MPO release to the inflammation site, and found a marked inhibition of MPO levels by all extracts and fractions, even superior to the inhibition shown by indomethacin.Furthermore, in the MPO in vitro assay, IMNGD, PsQ, PsS, PsT and PsU, exhibited higher inhibition levels compared to dexamethasone and indomethacin. In the NO release in vitro, IMNGD, PsP and PsT were the most potent treatments. Finally, because the PsG, PsP and seco-PsK did not exhibit any NO scavenger activity, they should inhibit the inducible Nitric Oxide Synthase (iNOS) or other routes that influence this enzyme. Alternatively, PsQ, PsS, and PsU did show scavenger activity. CONCLUSION: All results presented contribute to demonstrate that the compounds isolated in this work from P. elisabethae are promising molecules with an interesting anti-inflammatory activity profile. Additionally, the results obtained could provide preliminary insights towards their structure-activity relationship.

Determining the pharmacological activity of Physalis peruviana fruit juice on rabbit eyes and fibroblast primary cultures.

PURPOSE: The pharmacologic activity of compounds isolated from Physalis peruviana has been demonstrated. The use of this fruit juice for treating pterygium has been reported in Colombian traditional medicine. However, studies demonstrating the fruit juice's pharmacologic activity when used in this disease have not been published to date. In the present study the anti-inflammatory and cytostatic activities of P. peruviana fruit juice in a rabbit eye inflammatory model were investigated. METHODS: A novel rabbit eye inflammation model was developed for studying the juice's anti-inflammatory activity (based on an adaptation of the Draize test). Cytostatic activity was evaluated by measuring and comparing growth rates of cultured fibroblasts exposed and not exposed to various fruit juice concentrations. RESULTS: P. peruviana fruit juice exhibited a mild anti-inflammatory activity compared with methylprednisolone, a known anti-inflammatory drug. An interesting dose-dependent cytostatic effect on cultured fibroblasts was also established. CONCLUSIONS: The data found suggest that the P. peruviana fruit juice anti-pterygium effect described in traditional medicine may be related to its inhibiting fibroblast growth. The present study contributes to the pharmacologic knowledge regarding a remedy commonly used in Colombian traditional medicine.

Evaluación de extractos y fracciones de plantas colombianas en modelos de inflamación aguda, subcrónica y crónica / Evaluation of acute, subchronic and chronic inflammation activity of extracts and extracts fractions of Colombian plants

Se evaluó la actividad antiinflamatoria de extractos y fracciones de Acnistus arborescens, Baccharis latifolia, Myrcianthes leucoxila, Physalis peruviana y Salvia rubescens en los modelos in vivo de inflamación edema tópico en oreja de ratón, edema plantar por carragenina en rata y bolsa de aire en ratón, con profundización en modelo de artritis por adyuvante en rata. Inicialmente se realizó el screening de un total de 34 fracciones en el modelo de edema auricular en ratón, de los cuales se seleccionaron dos de Acnistus arborescens, cuatro de Baccharis latifolia y de Myrcianthes leucoxila y dos de Salvia rubescens. Posteriormente se evaluó la actividad de dichas fracciones en el modelo de edema plantar por carragenina en rata seleccionando aquellos que mostraron mayor actividad para ser evaluados luego en el modelo de bolsa de aire en ratón. Después de esta evaluación continuaron el estudio las fracciones S2 y S7 de S. rubescens, provenientes del extracto hidroalcohólico, y AA-F de A. arborescens, que corresponde a la fracción de diclorometano. La última fase correspondió a la evaluación de S2 y AA-F en el modelo de artritis por adyuvante en ratas Wistar, que empleó el protocolo de evaluación de actividad preventiva en el desarrollo de artritis y se observó que no ejercieron dicha actividad.

Some extracts and fractions of Acnistus arborescens, Baccharis latifolia, Myrcianthes leucoxila, Physalis peruviana and Salvia rubescens were examined for antiinflammatory activity in vivo models as mice ear oedema, carrageenan induced rat paw oedema, zimosan injected-rat air pouch and Freund's adjuvant arthritis. In initial screening on mice ear oedema model were selected two of A. arborescens, four of B. latifolia and M. leucoxila and two of S. rubescens among thirty four fractions which showed greater antiinflammatory activity. Later, these fractions were evaluated in carrageenan induced rat paw oedema model and those that showed greater activity have been selected to be evaluated in the zimosan injected-mice air pouch model. S2 and S7 fractions of S. rubescens, that came from hydroalcoholic extract, and AA-F of A. arborescens, that corresponded diclorometane fraction, were those that until this phase of the study showed greater antiinflammatory activity. The last phase corresponded to the evaluation of S2 and AA-F in the model Freund's adjuvant arthritis in Wistar rats using the protocol of evaluation of preventive activity in the development of arthritis showed that did not exhibit this activity.

Evaluación preliminar de la actividad hipoglicemiante en ratones diabéticos por aloxano y capacidad antioxidante in Vitro de extractos de Bauhinia kalbreyeri Harms / Preliminary evaluation of hypoglycemic activity in diabetic mice and in vitro antioxidant activity of Bauhinia kalbreyeri Harms extracts

Bauhinia kalbreyeri (Casco de vaca) es una planta tropical de la familia Caesalpinaceae. Sus hojas sirvieron de base para obtener un extracto etanólico con el cual se realizaron dos bioensayos con el fin de determinar la actividad hipoglicemiante de la planta. El estudio se complementó evaluando la actividad antioxidante por el método del radical libre DPPH y realizando un análisis fitoquímico preliminar. La diabetes se indujo en ratones normoglicémicos mediante la administración de aloxano en dosis de 75 mg/Kg. Los animales que resultaron diabéticos fueron asignados a diferentes grupos para ser sometidos a tratamiento con el extracto (1000 mg/Kg), el disolvente de los tratamientos (control), la tolbutamida (patrón, vía oral) y la insulina (vía subcutánea). En los bioensayos se realizaron comparaciones mediante un análisis de varianza (ANOVA). La dosis única de 1000 mg/Kg no disminuyó los niveles de glucosa sanguínea en ratones con diabetes tipo I (insulino dependiente). No obstante, los extractos etanólicos y acuosos de hoja y corteza de la planta mostraron capacidad atrapadora de radicales libres comparable al ácido ascórbico, utilizado como patrón. La actividad antioxidante de los extractos podría estar relacionada con el uso de la planta como antidiabético dado en la etnobotánica y ser consecuencia de la abundante cantidad de metabolitos tipo fenólico encontrados

Evaluación de actividades enzimáticas elastasa y mieloperoxidasa como marcadores de desgranulación leucocitaria en modelos de inflamación aguda / Evaluation of some enzymatic activities as markers of leukocyte degranulation in acute inflammation models

El efecto antiinflamatorio de sustancias aisladas de plantas medicinales colombianas fue evaluado mediante dos modelos de inflamación aguda: edema auricular inducido por TPA en ratón y bolsa de aire / zimosán en rata, encontrándose resultados promisorios (ej. actividades evidentes in vitro a concentración 100 M) para amarisolide, un clerodano aislado de Salvia rubescens y los glicósidos de ésteres alifáticos aislados de cálices de Physalis peruviana. Adicionalmente, se evaluó mediante métodos colorimétricos el potencial efecto inhibitorio sobre la liberación y la actividad elastasa y mieloperoxidasa (MPO), dos enzimas de desgranulación neutrofílica implicadas en procesos inflamatorios. Los resultados apuntan a que parte del efecto antinflamatorio de dichas sustancias se debe a actividad directa y/o indirecta sobre estas enzimas

Estudio fitofarmacológico de Senna spectabilis (D.C) I&B / Phytopharmacology study of Senna spectabilis (D.C.)I&B

Se realizó el estudio fitofarmacológico de Senna spectabilis. Se efectuó la extracción de los alcaloides de la corteza de la planta y se determinó su actividad farmacológica y su toxicidad. Se demostró un efecto anticoagulante de los alcaloides totales y se logró reproducir en el animal experimental las alteraciones hematológicas. Los alcaloides muestran un aumento de la actividad motriz espontánea, inferior a la producida por la anfetamina, pero notoria en la dosis de 25 mg/Kg. La administración de los alcaloides a los animales de experimentación produce, además, convulsiones. Se determinó en ratones la DL50 de los alcaloides totales, obteniéndose un resultado de 31 mg/Kg de peso. Se efectuó un estudio histopatológico de algunos órganos de las ratas y ratones utilizados en los ensayos de actividad farmacológica y se observaron daños ocasionados por la administración de los alcaloides totales