Ursolic acid increases strength in mdx mice model and may decrease fibrosis deposition by tgf-ß downregulation / El ácido ursólico aumenta la resistencia en el modelo de ratones mdx y podría disminuir la deposición de fibrosis mediante la regulación decreciente de tgf-ß

SUMMARY: Dystrophin disfunction results in sarcolemma destabilization, leading muscle cell damage by continuous degeneration cycles and limited regeneration. In muscle dystrophy, caused by dystrophin dysfunction, inflammation, necrosis and fibrosis are pathophysiological muscle function loss characteristics. As a genetic disease, this muscle dystrophy has no cure, however, advances in drug therapy using glucocorticoids can decrease the disease progression. Subsequently, alternative therapies were studied, such as ursolic acid (UA), that inhibits muscle atrophy and increases muscle mass and strength. Herein, we used 10 mg/kg daily supplementation in mdx mice for 4 weeks to evaluate serum creatine phosphokinase (CPK), muscle strength (Kondziela test), muscular organization (histology) and expression of fibrosis related genes (TGF-ß, TNF-α, mstn and ostn). UA supplementation increased muscle morphological organization, motor strength and decreased muscular TGF-ß expression. Altogether, the gene expression profile, histological organization and strength could suggest that UA treatment did not stop the fibrogenesis but decreased its progress.

RESUMEN: La disfunción de la distrofina resulta en la desestabilización del sarcolema, llevando al daño de las células musculares por ciclos continuos de degeneración y regeneración limitada. En la distrofia muscular, debido a la disfunción de la distrofina, la inflamación, la necrosis y la fibrosis, son características fisiopatológicas de la pérdida de la función muscular. Como enfermedad genetica no es possible remediar esta distrofia muscular, sin embargo, los avances en la terapia de medicamentos con glucocorticoides pueden disminuir la progresión de la enfermedad. Se estudiaron terapias alternativas, como el ácido ursólico (UA), que inhibe la atrofia muscular y aumenta la masa y la fuerza muscular. En este estudio, utilizamos una suplementación diaria de 10 mg / kg en ratones mdx durante 4 semanas para evaluar la creatina fosfoquinasa (CPK) sérica, la fuerza muscular (prueba de Kondziela), la organización muscular (histología) y la expresión de genes relacionados con la fibrosis (TGF-ß, TNF- α, mstn y ostn). La suplementación con AU aumentó la organización morfológica muscular, la fuerza motora y la disminución de la expresión muscular de TGF-ß. El perfil de expresión génica, la organización histológica y la fuerza simultáneamente podrían sugerir que el tratamiento con AU no detuvo la fibrogénesis sino que disminuyó su progreso.

α, ß-Amyrin prevents steatosis and insulin resistance in a high-fat diet-induced mouse model of NAFLD via the AMPK-mTORC1-SREBP1 signaling mechanism

Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,β-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.

Vascular mechanisms of monodesmosidic triterpene saponins isolated from Passiflora quadrangularis L / Mecanismos vasculares de saponinas triterpénicas monodesmosídicas aisladas de Passiflora quadrangularis L

Background: Passiflora quadrangularis L. has antihypertensive and anxiolytic properties observed in experimental models. Objectives: The aim of this work was to establish the vascular effects exerted by two known monodesmosidic triterpene saponins, 3-O-ß-D-glucopyranosyloleanolic acid (Compound 1) (not previously described for this plant) and, 3-O-[ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl] oleanolic acid (Compound 2), isolated from the ethanolic extract of Passiflora quadrangularis L. leaves. Methods: The structural elucidation was achieved by Nuclear Magnetic Resonance (NMR) experiments and High-Resolution Mass Spectrometry (HRMS). Aortic rings from Wistar rats, previously stimulated with phenylephrine (PE, 1µM) and washed, were exposed to cumulatively concentrations of compound 1 and compound 2 (10 to 400 µM). Ethanolic extract from leaves of P. quadrangularis L. (10 to 320 µg/ mL) and clonidine (1nM to 100µM) were also used for comparison. Concentration response curves of compounds 1 and 2 were examined in presence and absence of: endothelium, the alpha-2 antagonist yohimbine (1 and 100 µM), the alpha non selective antagonist phentolamine (1µM), the alpha-1 antagonist prazosin (1µM) and the calcium channel blocker verapamil (10 and 100 µM). In addition, cumulatively response curve of acetylcholine (ACh, 10nM to 10µM) and sodium nitroprusside (SNP, 1nM to 100µM) were assayed in rings precontracted with compounds 1 and 2 (400 µM). Results: Compounds 1 and 2 elicited a vasoconstriction response in intact aorta rings in similar way (pEC50: 3.92±0.01 and 4.09±0.01, respectively), effect that did not change in denuded rings (pEC50: 3.90±0.01 and 4.11±0.01). The potency order (pEC50) of compounds 1 and 2 decreased according to the following: verapamil (3.53±0.01 and 3.90±0.02; p<0.05) < yohimbine (3.65±0.01 and 3.94±0.02; p<0.05) < prazosin (3.86±0.01 and 4.30±0.02) < phentolamine (4.05±0.02 and 4.05±0.01). SNP but not ACh, was able to decrease the vasopressor effect of compounds 1 and 2 (pIC50: 8.61±0.01 and 8.24 ± 0.15, respectively). Conclusions: Compounds 1 and 2 are key metabolites responsible for the ex vivo vasoconstrictor response induced by P. quadrangularis L. Activation of voltage-dependent calcium channels and/or α2-adrenergic receptors stimulation could be mechanisms implicated.

Antecedentes: Passiflora quadrangularis L. tiene propiedades antihipertensivas y ansiolíticas observadas en modelos animales. Objetivos: El objetivo de este trabajo fue establecer los efectos vasculares ejercidos por dos conocidas saponinas triterpénicas monodesmosídicas: el ácido 3-O-ß-D glucopiranosiloleanólico (Compuesto 1) (no descrito previamente para esta especie vegetal) y el ácido 3-O-[ß-D-glucopiranosil- (1→2)-ß-D-glucopiranosil]oleanólico (Compuesto 2), aisladas del extracto etanólico de las hojas de Passiflora quadrangularis L. Métodos: La elucidación estructural se llevó a cabo mediante experimentos de Resonancia Magnética Nuclear (NMR) y determinaciones de Espectrometría de Masas de Alta Resolución (HRMS). Los anillos aórticos de ratas Wistar, previamente estimulados con fenilefrina (PE, 1 µM) y lavados, fueron expuestos a concentraciones acumulativas del compuesto 1 y compuesto 2 (10 a 400 µM). El extracto etanólico de las hojas de P. quadrangularis L. (10 a 320 µg / ml) y clonidina (1 nM a 100 µM) se utilizaron para la comparación. Las curvas de concentración respuesta de los compuestos 1 y 2 se examinaron en presencia y ausencia de: endotelio, el antagonista alfa-2 yohimbina (1 y 100 µM), el antagonista alfa no selectivo fentolamina (1 µM), el antagonista alfa-1 prazosina (1 µM) y el bloqueador de canales de calcio verapamilo (10 y 100 µM). Además, la curva de concentraciones acumulativas de acetilcolina (ACh, 10 nM a 10 µM) y nitroprusiato de sodio (SNP, 1 nM a 100 µM) se ensayó en anillos pre-contraídos con los compuestos 1 y 2 (400 µM). Resultados: Los compuestos 1 y 2 provocaron una respuesta de vasoconstricción en los anillos de aorta intactos de manera similar (pEC50: 3.92 ± 0.01 y 4.09 ± 0.01, respectivamente), este efecto no cambió en los anillos denudados (pEC50: 3.90 ± 0.01 y 4.11 ± 0.01). El orden de potencia (pEC50) de los compuestos 1 y 2 disminuyó de la siguiente manera: verapamilo (3.53 ± 0.01 y 3.90 ± 0.02; p <0.05) < yohimbina (3.65 ± 0.01 y 3.94 ± 0.02; p <0.05) < prazosina (3.86 ± 0.01 y 4.30 ± 0.02)

Alpha-hederin induces the apoptosis of oral cancer SCC-25 cells by regulating PI3K/Akt/mTOR signaling pathway

BACKGROUND: Oral cancer is one of the common malignant tumors of the head and neck. However, current treatments have numerous side effects, and drugs from natural sources may have better therapeutic potential. This research investigated the induction of apoptosis by α-hederin (α-HN), a constituent of Pulsatilla chinensis (Bunge) Regel, in the oral cancer cell line SCC-25 and its underlying mechanism. RESULTS: SCC-25 cells were treated with 50, 100, and 200 µmol/L α-HN. Cell proliferation; extent of apoptosis; activities of caspases-3, 8, and 9; and the expression of Bcl-2, Bax, phosphorylated (p)-phosphoinositide 3-kinase (PI3K), p-Akt, and p-mammalian target of rapamycin (mTOR) proteins were determined using the 3-(4,5)-2-thiazole-(2,5)-diphenyl tetrazolium bromide, flow cytometry, caspase activity detection kits, and western blot assays, respectively. The results showed that the proliferation of SCC-25 cells in the α-HN-treated groups decreased significantly, and the inhibitory effect was time and concentration dependent. Compared with cells in the control group, the extent of apoptosis increased significantly, caspase-3 and -9 activities were significantly enhanced, and the Bcl-2 level was lowered and the Bax level was elevated significantly in SCC-25 cells treated with α-HN for 48 h (P b 0.05). The expression of p-PI3K, p-Akt, and p-mTOR was also significantly lower in SCC-25 cells treated with α-HN than that in the control group (P b 0.05). CONCLUSION: These results indicate that α-HN can inhibit proliferation and induce apoptosis of SCC-25 cells and may exert these effects by inhibiting the PI3K/Akt/mTOR signaling pathway.

Oleanonic acid from Lippia lupulina (Verbenaceae) shows strong in vitro antileishmanial and antitrypanosomal activity / Ácido oleanônico isolado de Lippia lupulina (Verbenaceae) apresenta potentes atividades leishmanicida e tripanocida

Leishmaniasis and Chagas disease affect millions of people in tropical and subtropical regions. Drugs used currently to treat such diseases often present undesirable side effects and low efficiency. The aim of this work was to identify extracts and isolated compounds from the genus Lippia with leishmanicidal and trypanocidal activity. Fifteen extracts from different plant parts of Lippia species with partially known chemical compositions, four partition fractions, six compounds and a mixture of four interconverting flavanones previously isolated from Lippia salviaefolia and Lippia lupulina were assayed in vitro towards epimastigote forms of Trypanosoma cruzi and promastigote forms of Leishmania amazonensis. The root extract of L. lupulina had potent activity against T. cruzi and L. amazonensis (IC50 of 20.0 and 54.5 µg mL-1, respectively). The triterpenoid oleanonic acid showed the strongest activity against these protozoans (IC50 of 18.5 and 29.9 µM, respectively). Our results indicate that Lippia plants and their derivatives deserve further investigation in the search for new antiprotozoal drugs, particularly for the treatment of leishmaniasis and Chagas disease.

Leishmaniose e doença de Chagas afetam milhões de pessoas em regiões tropicais e subtropicais. As drogas atualmente usadas para tratar estas doenças frequentemente apresentam efeitos colaterais indesejáveis e baixa eficiência. Este trabalho teve como objetivo encontrar extratos, frações e compostos isolados de espécies do gênero Lippia com atividades leishmanicida e tripanocida. Quinze extratos de diferentes partes de plantas do gênero Lippia, com composições químicas parcialmente conhecidas, quatro frações de partição, seis substâncias e uma mistura de quatro flavanonas interconversíveis isolados de Lippia salviaefolia e Lippia lupulina foram testados, in vitro, frente a formas epimastigotas de Trypanosoma cruzi e promastigotas de Leishmania amazonensis. O extrato etanólico das raízes de L. lupulina apresentou atividade potente contra T. cruzi e L. amazonensis (IC50 de 20,0 e 54,5 µg mL-1, respectivamente), enquanto que o ácido oleanônico mostrou as atividades mais fortes contra estes protozoários, com IC50 de 18,5 e 29,9 µM, respectivamente. Estes resultados indicam que espécies do gênero Lippia e seus derivados merecem investigações adicionais na busca por novas terapias antiprotozoárias, especialmente para o tratamento de leishmaniose e doença de Chagas.

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.

Oleanolic acid and ursolic acid inhibit peptidoglycan biosynthesis in Streptococcus mutans UA159

In this study, we revealed that OA and UA significantly inhibited the expression of most genes related to peptidoglycan biosynthesis in S. mutans UA159. To the best of our knowledge, this is the first report to introduce the antimicrobial mechanism of OA and UA against S. mutans.

Intervenção nas situações de crise psíquica: dificuldades e sugestões de uma equipe de atenção pré-hospitalar / Intervention in situations of psychic crisis: challenges and suggestions of a prehospital care staff / Intervención en situaciones de crisis psíquica: problemas y sugerencias de un equipo de atención prehospitalaria

Pesquisa descritiva, qualitativa, que objetivou conhecer como os profissionais de atenção pré-hospitalar percebem as intervenções nas pessoas em crise psíquica. O estudo foi realizado, no estado de Santa Catarina, com quatro equipes das Unidades de Suporte Básico do Serviço de Atendimento Móvel de Urgência, mediante entrevista, no período de abril a junho de 2011. Utilizou-se como método de análise o Discurso do Sujeito Coletivo. Dos resultados emergiram dois temas: Percepção das dificuldades no atendimento à pessoa em crise psíquica e Sugestões na busca por um atendimento mais próximo do desejado à pessoa em crise psíquica. As dificuldades apontadas se relacionam à falta de capacitação e de um local para encaminhamento e sugerem treinamento e sistematização do atendimento. Conclui-se que se faz necessário investir em processo de formação pautado em novas estratégias de cuidado norteadas pelos princípios do SUS e no paradigma psicossocial, além de rediscutir a estratégia de protocolos como sistemas norteadores e não padronizadores.

A qualitative and descriptive research, aimed at knowing how the pre-hospital care professionals perceive the interventions towards people in mental crisis. The study was developed in Santa Catarina with four teams of basic life support units of the Department of Mobile Emergency Care, during April to June 2011. The Collective Subject Discourse was used as the method of analysis. Two themes emerged: Awareness of the difficulties in meeting a person in mental crisis and Suggestions in the search for a closer attention to the person in mental crisis. The difficulties mentioned were related to the lack of training and a local to forward the patients, suggesting a better training and systematization of care. We conclude that it is necessary to invest in the educational process, based on new care strategies guided by the principles of SUS and of the psychosocial paradigm, and revisit the strategy of protocols as guidelines and not as standardizing systems.

Investigación descriptivo-cualitativa, que objetivó conocer como los profesionales de la atención pre-hospitalaria perciben las intervenciones en personas con crisis mental. El estudió fue realizado en Santa Catarina con cuatro equipos de las Unidades de Soporte Vital Básico, mediante entrevista realizada de abril a junio de 2011. El Discurso del Sujeto Colectivo fue utilizado como método de análisis; surgiendo dos temas: Percepción de las dificultades en la atención a la persona en crisis mental y Sugerencias en la búsqueda de una mejor atención a la persona en crisis mental. Las dificultades mencionadas se relacionan con la falta de capacitación y lugar para la atención, sugiriendo un mejor entrenamiento y sistematización de la atención. Se resalta la necesidad de invertir en el proceso de formación basado en nuevas estrategias de atención guiadas por los principios del SUS y el paradigma psicosocial, y revisar la estrategia de protocolos como nortes no estandarizados.

Compositional studies and Biological activities of Perovskia abrotanoides Kar. oils

BACKGROUND: Current study has been designed to evaluate the chemical composition of essential and fixed oils from stem and leaves of Perovskia abrotanoides and antioxidant and antimicrobial activities of these oils. RESULTS: GC-MS analysis of essential oil identified 19 compounds with (E)-9-dodecenal being the major component in stem and hexadecanoic acid in leaves. In contrast, GC-MS analysis of fixed oil showed 40 constituents with α-amyrin the major component in stem and α-copaene in leaves. The antioxidant activity showed the highest value of 76.7% in essential oil from leaves in comparison with fixed oil from stem (45.9%) through inhibition of peroxidation in linoleic acid system. The antimicrobial assay tested on different microorganisms (e.g. E. coli, S. aureus, B. cereus, Nitrospira, S. epidermis, A. niger, A. flavus and C. albicans) showed the higher inhibition zone at essential oil from leaves (15.2 mm on B. cereus) as compared to fixed oil from stem (8.34 mm onS. aureus) and leaves (11.2 mm on S. aureus). CONCLUSIONS: The present study revealed the fact that essential oil analyzed from Perovskia abrotanoides stem and leaves could be a promising source of natural products with potential antioxidant and antimicrobial activities, as compared to fixed oil.

Pesticidal and pest repellency activities of a plant derived triterpenoid 2α, 3ß, 21ß, 23, 28-penta hydroxyl 12-oleanene against Tribolium castaneum

BACKGROUND: Tribolium castaneum (Herbst) is a major pest of stored grain-based products, and cause severe damage to cereal grains throughout the world. The present investigation was aimed to determine the pesticidal and pest repellent activities of 2α,3ß,21ß,23,28-penta hydroxyl 12-oleanene against T. castaneum. The compound 2α,3ß,21ß,23,28-penta hydroxyl 12-oleanene is a triterpenoid which was isolated from the roots of Laportea crenulata Gaud. Surface film technique was used for pesticidal screening, whereas, pest repellency property of the triterpenoid was determined by filter paper disc method. RESULTS: At 24 hours of exposure duration, significant mortality records (80% and 86%) were observed at doses 0.88 and 1.77 mg/cm². No significant change in mortality records was observed when duration of exposure was increased up to 48 hours. The triterpenoid showed significant repellency activity at doses 0.47 and 0.94 mg/cm². CONCLUSION: These data suggest that the triterpenoid 2α,3ß,21ß,23,28-penta hydroxyl 12-oleanene possess both pesticidal and pest repellency activities against T. castaneum and can be used in controlling the pest of grain-based products.

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).

Variation in concentrations of major bioactive compounds in Prunella vulgaris L. related to plant parts and phenological stages

Prunella vulgaris L. (Labiatae) contains a variety of structurally diverse natural products, primarily rosmarinic acid (RA), ursolic acid (UA) and oleanolic acid (OA), which possess a wide array of biological properties. In the present study, P. vulgaris was harvested at three developmental stages (vegetative, full-flowering and mature-fruiting stages), dissected into stem and leaf tissues and assayed for chemical contents using high performance liquid chromatography. Significant changes in the concentrations of the major secondary metabolites (RA, UA and OA) were observed at the different development stages. The highest concentrations of RA, UA and OA were found at the full-flowering stage (15.83 mg/g dry weight (DW) RA, 1.77 mg/g DW UA and 0.65 mg/g DW OA). Among the different aerial parts of the plant, the concentrations of RA, UA and OA were higher in the leaves than in the stems at the different developmental stages. These results suggest that the full-flowering stage is characterized by the highest concentrations of bioactive compounds. Therefore, this stage may be the optimum point for harvesting P. vulgaris plants. In additional, the leaves of P. vulgaris demonstrated higher RA, UA and OA concentrations than the stems, suggesting higher utilization potential.

Effect of bioactive compounds extracted from euphorbious plants on hematological and biochemical parameters of Channa punctatus / Efeito de compostos bioativos extraídos de plantas eufórbicas sobre os parâmetros hematológicos e bioquímicos da Channa punctatus

Channa punctatus was exposed to four different concentrations of Rutin, Taraxerol and Apigenin. Changes in some hematological parameters of Channa punctatus were assessed to determine the influence of these compounds on test fish. Fish were exposed to sublethal concentrations (80 percent of LC50 of 24h) of these compounds for one week. Control fish were also administered for one week. Thereafter, blood samples were obtained from the control and experimental fish. Blood was assayed for selected hematological parameters (hematocrit, hemoglobin, red blood cell count, white blood cell count total plasma protein and plasma glucose concentration). The derived hematological indices of mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) were calculated. Sublethal concentrations of these compounds caused a dose dependent decrease in hemoglobin values coupled with a decrease in hematocrit values and red blood cell counts are an obvious indication of anemia. The total white blood cell counts and the differential white blood cell counts were decreased except for the lymphocytes, where there was a slight increase. Plasma protein and glucose were also lower in exposed fish when compared with control. The hematological indices MCH, MCHC, MCV were also lowered. The result from this study reveals high mortality rate and deleterious consequences on the health of fish subjected to acute exposure of Rutin, Taraxerol and Apigenin and therefore, should not be used directly in aquaculture without having the proper knowledge.

Channa punctatus foi exposta a quatro diferentes concentrações de Rutina, Taraxerol e Apigenina. Alterações de alguns parâmetros hematológicos da Channa punctatus foram acessados para determinar a influência destes compostos no peixe teste. Peixes foram expostos a concentrações sub-letais (80 por cento 0f LC50 em 24h) destes compostos por uma semana. Os peixes controles foram também expostos durante uma semana. A seguir, amostras de sangue foram obtidas do peixe controle e do experimental. O sangue foi estudado por parâmetros hematológicos selecionados (hematócrito, hemoglobina, contagem de células vermelhas e brancas, proteína plasmática total e concentração de glucose plasmática). Os índices hematológicos derivados da média da concentração corpuscular da hemoglobina (MCHC), a média de hemoglobina corpuscular (MCH) e a média de volume corpuscular (MCV), foram calculados. Concentrações sub-letais destes compostos causaram decréscimo dose-dependente dos valores da hemoglobina unidos a decréscimo de valores de hematócrito e das contagens de células sanguíneas vermelhas o que caracteriza indicação óbvia de anemia. As contagens totais de células brancas e a contagem diferencial destas células estavam diminuídas exceto pelos linfócitos que mostraram leve aumento. A proteína plasmática e a glicose estavam também baixas nos peixes expostos quando comparados com o controle. Os índices hematológicos MCH, MCHC, MCV estavam também diminuídos. Os resultados deste estudo revelam alto percentual de mortalidade e conseqüências deletérias à saúde de peixes submetidos à exposição aguda de Rutina, Talaxerol e Apigenina e portanto eles não devem ser usados diretamente em aquacultura sem conhecimento apropriado.

Impact of Taraxerol in combination with extract of Euphorbia tirucalli plant on biological parameters of Lymnaea acuminata / Impacto do Taraxerol em combinação com o extrato da planta de Euphorbia tirucalli nos parâmetros biológicos da Lymnaea acuminata

The present work was carried out to evaluate the molluscicidal activity of active ingredient Taraxerol with the acetone extract of Euphorbia tirucalli against Lymnaea acuminata snail. The (fecundity, hatchability and survivability) of snail L. acuminata exposed to this extract was studied. The effects of the tested extracts on life-history traits of harmful snail L. acuminata have also been evaluated, and this study also expounds the inhibitory effects of these extracts singly as well as in binary combination (1:1 ratio). It concluded that these herbal products act as a potential source of molluscicides, and that they would also have the advantage of easy availability, low cost, biodegradability and greater acceptance amongst users than synthetic pesticide.

O presente trabalho foi levado a efeito para avaliar a atividade moluscicida do ingrediente ativo Taraxerol junto com o extrato de acetona da Euphorbia tirucalli contra o caramujo Lymnaea acuminata. Foram estudados a fecundidade, o desenvolvimento e sobrevivência do caramujo Lymnaea acuminata exposto a estes extratos. Os efeitos danosos destes extratos testados na vida do caramujo L. acuminata foram também avaliados e este estudo demonstra os efeitos inibidores destes extratos isolados ou em combinação binária (relação l:1). Concluiu-se que estes produtos vegetais agem como fontes potenciais de moluscicidas e que eles também têm a vantagem de obtenção fácil, baixo custo, biodegradabilidade e maior aceitação entre os usuários do que os pesticidas sintéticos.

Estudo do potencial terapêutico dos triterpenos pentacíclicos ácido betulínico, ácido oleanólico e ácido ursólico no tratamento da obesidade em camundongos [manuscrito] / Study of the therapeutic potential of pentacyclic triterpenes betulinic acid, oleanolic acid and ursolic acid in the treatment of obesity in mice [manuscript]

A obesidade é uma epidemia global, com uma prevalência crescente tanto em países desenvolvidos quanto em desenvolvimento. Está associada a uma carga considerável de problemas de saúde e um risco aumentado para doença arterial coronariana e síndrome metabólica. O vasto potencial da natureza para o tratamento da obesidade ainda não foi totalmente explorado, embora alguns estudos científicos tenham descrito efeitos benéficos de inumeráveis fitoquímicos. Atualmente, a classe de compostos químicos conhecidos como terpenos tem sido o foco de maior atenção por apresentarem uma grande variedade de ações bioquímicas e farmacológicas capazes de reduzir o excesso de gordura corporal e prevenir a diabetes e doenças cardíacas. O objetivo deste trabalho foi avaliar o provável efeito antiobesidade dos triterpenos pentacíclicos ácido betulínico (AB), ácido ursólico (AU) e ácido oleanólico (AO), isolados de plantas medicinais tradicionais do Norte e Nordeste do Brasil. Os camundongos foram alimentados com dietas normocalórica ou hipercalórica e tratados simultaneamente com as drogas na concentração de 50 mg/mL ad libitum durante 15 semanas. Semanalmente o peso corporal e diariamente o consumo de água e alimentos foram registrados e, ao final deste período, amostras de sangue heparinizado foram coletadas para determinação dos exames laboratoriais (glicemia, GLI; colesterol total, CT; HDL-Colesterol, HDL-C; triglicerídios, TG; grelina; leptina; insulina; α-amilase; lipase; aspartato aminotransferase, AST; alanina aminotransferase, ALT e fosfatase alcalina, ALP)...

Efeitos dos triterpenóides ácidos oleanólico e ursólico em ratos F344 submetidos ao modelo de hepatocarcinogênese do ®hepatócito resistente¼ / Effects of the triterpenoids oleanolic acid and ursolic acid in rat F344 submitted to the resistant hepatocyte model of hepatocarcinogenesis

Avaliou-se os efeitos dos ácidos oleanólico (AO) e ursólico (AU), triterpenóides presentes em alimentos vegetais e especiarias, quando administrados a ratos F344 durante as etapas de iniciação e seleção/promoção do modelo de hepatocarcinogênese do ®hepatócito resistente¼ (RH). Os ratos receberam durante 8 semanas, por entubação gástrica e dissolvido em óleo de milho (OM): AO ou AU (8 mg/100 g de peso corpóreo [p.c]). Os grupos controle receberam apenas OM (0,25 mL/100 g de p.c; grupo OM), ou água (0,25 mL/100 g de p.c; grupo Água). O grupo Normal não recebeu qualquer tratamento. O agente iniciante foi uma dose de dietilnitrosamina (DEN, 20 mg/100 g de p.c.). Após 2 semanas de entubação, aplicou-se 3 doses diárias consecutivas de 2-acetilaminofluoreno (2-AAF)(2 mg/100 g de p.c.) e fez-se uma hepatectomia parcial a 70 por cento, acrescida de 1 dose de 2-AAF (0,5 mg/100 g de p.c.) 4 dias após a cirurgia...

It was evaluated the effects of the oleanólico acid (OA) and ursolic acid (UA), triterpenoids present in vegetable foods and spices, when administered to rat F344 during the initiation and selection/promotion stages of the resistant hepatocyte model of hepatocarcinogenesis RH. The rat received for 8 weeks, by gavage and dissolved in com oil (CO): OA or UA (8 mg/100 g of body weight [b.w.]). The control groups just received CO (0,25 mL/100 g b.w.; CO group), or water (0,25 mL/100 g b.w.; group Water). Normal group did not receive any treatment type. The initiation agent was dietilnitrosamine (DEN, 20 mg/100 g b.w.). 2 weeks after gavage, it was applied 3 consecutive doses of 2-acetilaminofluoreno (2-AAF) (2 mg/100 g of b.w.) and it was made a 70% partial hepatectomy, added of 1 dose of 2-AAF (0,5 mg/100 9 b.w.) 4 days after the surgery. In 6 weeks after the initiation, the animals were sacrificed. Results: the macroscopic analysis demonstrated that OA did not alter and UA tended to increase the number of hepatocytes nodules, compared to the CO group. The morphometric analysis of the pre-neoplastic lesions (PNL) positive for glutatione S-transferase placentary form (GST-p), demonstrated that OA and UA did not alter the medium number of persistent LPN, however they reduced the medium number of remodeling LPN, compared to the OM group (p <0,05). OA and UA did not alter the medium area of persistent LPN, but they reduced the medium area of remodeling LPN, compared to the CO group (p <0,05). The triterpenoids did not alter the occupied area of the section for persistent LPN, but they reduced the occupied area cut for remodeling LPN, compared to the CO group (p <0,05). The Water, OM and AU groups showed increase in the plasmatic concentration of cholesterol, compared to the Normal group. OA promoted increase of the expression of the gene that codifies for the HMG-CoA reductase enzyme, compared to the Normal group (p <0,05), and AU promoted increase expression when compared to the Normal, Water, OM and AU groups (p <0,05). OA and UA did not alter the indexes of cellular proliferation (imunoistochemistry for bromodeoxiuridine [BrdU)) in persistent LPN. AU promoted increase (p <0,05) in the cellular proliferation in remodeling LPN when compared to the CO group. OA and UA did not alter the apoptosis in persistent LPN, but they increased the medium number of apoptotics bodies in remodeling LPN (p <0,05). The Adjusted Index Growth (cellular apoptosis/proliferation) of the groups demonstrated that, in persistent LPN, the cellular proliferation has predominance on the apoptosis. In remodeling LPN, the apoptosis has preponderance over the cellular proliferation. The damages in hepatic DNA (method of the "comet") were larger in the group OA (p <0,05) and AU (p <0,061), compared to the CO group. The analysis for imunoblot revealed that the RH model increased the expression and the activation of the NF-κB transcription factor (p <0,05). OA and UA increased the expression and the activation of NF-κB, compared to the CO group (p> 0,05). It was...

A multidisciplinary approach to the study of the fluminense vegetation

The fluminense vegetation, more specifically the flora from the Jurubatiba restinga has been investigated by a multidisciplinary team of botanists, chemist, radiobiologist, insect physiologists and geneticist. Vouchers of 564 specimens have been collected, identified, organized in an herbarium, and a database is being build up containing, in addition to classical botanical data, chemical data and information on the potential economic use either for landscape gardening, alternative foods or as medicinal plants. Phytochemical studies of the Guttiferae, Clusia hilariana, yielded oleanolic acid and nemorosone. Their biological activities against the haematophagous insect Rhodnius prolixus vector of Chagas disease have been investigated. Finally, it has been observed that aquatic plants possessed high levels of the natural radionuclide polonium-210, which seems to be originated mainly from soil rather than from atmospheric supply

Efeito de constituintes químicos extraídos do fruto de Rheedia gardneriana (bacuparí) sobre bactérias patogênicas / Effect of chemical constituents from the fruit of Rheedia gardneriana (bacupari) on pathogenic bacteria

Rheedia gardneriana (bacupari) é planta da família Clusiaceae, encontrada na região Amazônica. A espécie estudada foi coletada no Horto Botânico da Universidade Federal de Viçosa. O estudo químico do fruto (pericarpo) conduziu à identificação dos seguintes constituintes: mistura de sesquiterpenos, ácido oleanóico e epiclusianona. Estes foram avaliados quanto ao potencial bactericida ou bacteriostático em testes in vitro. A epi-clusianona e o ácido oleanóico mostraram atividade inibitória no crescimento de Staphylococcus aureus e Listeria monocytogenes. A epi-clusianona inibiu o crescimento das fitobactérias Pseudomonas sp e Clavibacter michiganense subsp. michiganense

Determinación espectrofotometrica de ácido oleanólico y saponinas de quinua (Chenopodium quinoa Willd, variedad Kancolla) / Spectrophotometric determination of oleanolic acid and saponins from quinoa (Chenopodium quinoa Willd, Kancolla variety)

Las saponians de quinua (Chenopodium quinoa Willd., variedad Kancolla) fueron extraídas por reflujo con una mezcla de metanol-agua (4:1). Una vez evaporado el metanol, el residuo remanente fue tratado siguiendo el método de Honerlagen y Tretter con sólo pequeñas modificaciones. Luego, el extracto se sometió a hidrólisis con ácido sulfúrico 12/N en un sistema dioxano-agua (1:1) a 110-C por 15 horas. Las sapogeninas se extrajeron con cloroformo, concentradas, y algunos microlitros (equivalente a 121 mg de quinua) se sembraron contra un estándar de ácido oleanólico sobre placas de silicagel, siendo desarrollado con una mezcla de cloroformo-acetobabenceno (80:20:10; v/v). Las manchas se localizaron con vapores de yodo, y la banda cuyo Rf similar a la del ácido oleanólico, s eseparó e introdujo en una columna de vidrio; eluida con cloroformo, secada y disuelta en 1 ml de ácido acético glacial, fue tratada con 4 ml de una mezcla de ácido sulfúrico - ácido acético glacial (1:1; v/v), calentada en baño maría a 60-C por 25 minutos, enfriada y llevada al espectrofotómetro donde se leyó a 527 mm contra un blanco. Bajo las mismsa condiciones, el ácido oleanólico empleado como estándar mostró una linearidad en el rango de 60 a 480 microgramos. El porcentaje de ácido oleanólico ha sido determinado en quinua (0.269 ñ 0.25) y su contenido de saponinas fue estimado usando un factor de conversión establecido por cromatografía de gas y expresado en la siguiente rlación: % Saponinas = (8.5204) x (% Acido oleanólico). Las sapogneinas estraídas - analizadas por este método - acusaron un error de 10.7% en relación a su determinación por cromatografía de gas