RESUMEN

OBJECTIVES: The aim of this study was to investigate the in-vitro effect of rutin on glucose uptake in an insulin target (soleus muscle) and the mechanism of action involved. METHODS: Isolated soleus muscles from rats were treated with rutin (500 µm) with or without the following inhibitors; hydroxy-2-naphthalenylmethylphosphonic acid trisacetoxymethyl ester (HNMPA(AM)3 ), an insulin receptor tyrosine kinase activity inhibitor, wortmannin, an inhibitor of phosphatidylinositol 3-kinase (PI3K), RO318220, an inhibitor of protein kinase C, colchicine, a microtubule-depolymerizing agent, PD98059, an inhibitor of mitogen-activated protein kinase kinase (MEK), and cycloheximide, an inhibitor of protein synthesis on fresh Krebs Ringer-bicarbonate plus [U-(14) C]-2-deoxy-d-glucose (0.1 µCi/ml). Samples of tissue medium were used for the radioactivity measurements. KEY FINDINGS: Rutin increased the glucose uptake in rat soleus muscle. In addition, the effect of rutin on glucose uptake was completely inhibited by pretreatment with HNMPA(AM)3 , wortmannin, RO318220, colchicine, PD98059, and cycloheximide. These results suggested that rutin stimulated glucose uptake in the rat soleus muscle via the PI3K, atypical protein kinase C and mitogen-activated protein kinase (MAPK) pathways. Also, rutin may have influenced glucose transporter translocation and may have directly activated the synthesis of the transporter GLUT-4. CONCLUSION: The similarities of rutin action on glucose uptake compared with the signalling pathways of insulin constitute strong evidence for the insulin-mimetic role of rutin in glucose homeostasis.

Asunto(s)

Transportador de Glucosa de Tipo 4/biosíntesis , Glucosa/farmacocinética , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Rutina/farmacología , Animales , Western Blotting , Relación Dosis-Respuesta a Droga , Electroforesis en Gel de Poliacrilamida , Técnicas In Vitro , Insulina/farmacología , Masculino , Ratas , Ratas Wistar

RESUMEN

The aim of the study was to investigate the in vitro effect and the mechanism of action of kaempferitrin on glucose uptake in an insulin target (soleus muscle). A stimulatory effect of kaempferitrin on glucose uptake was observed when rat soleus muscle was incubated with 10, 100 and 1000 ηM of this flavonoid glycoside. The presence of specific insulin signaling inhibitors, such as wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K), RO318220, an inhibitor of protein kinase C (PKC), PD98059, an inhibitor of mitogen-activated protein kinase (MEK), HNMPA(AM)3, an insulin receptor tyrosine kinase activity inhibitor, colchicine, a microtubule-depolymerizing agent, SB239063, an inhibitor of P38 MAPK and cycloheximide, an inhibitor of protein synthesis showed that kaempferitrin triggers different metabolic and nuclear pathways in skeletal muscle. Besides the influence on glycogen storage, the metabolic action involves the insulin receptor, PI3K, atypical PKC activity and the translocation of GLUT4. Additionally, the nuclear pathways (via MAPK and MEK) provide evidence of the stimulation of the expression of glucose transporters or other signaling proteins, reinforcing proposals that skeletal muscle represents a primary site at which kaempferitrin exerts its effect promoting glucose homeostasis. Also, these similarities with the signaling pathways of insulin constitute strong evidence for the insulin-mimetic role of kaempferitrin in glucose homeostasis.

Asunto(s)

Glucosa/metabolismo , Insulina/metabolismo , Quempferoles/farmacología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Transporte Biológico/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Técnicas In Vitro , Insulina/farmacología , Masculino , Músculo Esquelético/citología , Ratas , Ratas Wistar

RESUMEN

A stimulatory effect of apigenin-6-C-ß-fucopyranoside (1) on glucose uptake was observed when rat soleus muscle was incubated with 1, 10 and 100 µM of this flavonoid glycoside. The presence of specific insulin signaling inhibitors, such as wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K), RO318220, an inhibitor of protein kinase C (PKC), PD98059, an inhibitor of mitogen-activated protein kinase (MEK), and HNMPA(AM)3, an insulin receptor tyrosine kinase activity inhibitor showed that apigenin-6-C-ß-fucopyranoside triggers different metabolic pathways in skeletal muscle. The oral administration of crude extract, fractions and isolated flavonoids (apigenin-6-C-ß-fucopyranoside (1) and apigenin-6-C-(2″-O-α-rhamnopyranosyl)-ß-fucopyranoside (2)) from Averrhoa carambola leaves exhibited a potential hypoglycemic activity in hyperglycemic normal rats. Additionally, both flavonoids significantly increased the muscle and liver glycogen content after an acute treatment. The results indicate that A. carambola can be regarded as a potent antihyperglycemic agent with insulin secretagogue and insulin mimetic properties.

Asunto(s)

Apigenina/uso terapéutico , Glucosa/metabolismo , Glicósidos/uso terapéutico , Hiperglucemia/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/metabolismo , Magnoliopsida/química , Fitoterapia , Administración Oral , Animales , Apigenina/farmacología , Glucógeno/metabolismo , Glicósidos/farmacología , Hiperglucemia/metabolismo , Hipoglucemiantes/farmacología , Secreción de Insulina , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Redes y Vías Metabólicas/efectos de los fármacos , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Músculo Esquelético , Inhibidores de las Quinasa Fosfoinosítidos-3 , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Hojas de la Planta , Proteína Quinasa C/antagonistas & inhibidores , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos

RESUMEN

UNLABELLED: This study was conducted to investigate the anti-inflammatory efficacy of Esenbeckia leiocarpa against the inflammation caused by the carrageenan using a murine air pouch model. MATERIAL AND METHODS: The effects of the crude hydroalcoholic extract (CHE), fractions (n-hexane (Hex) and ethyl acetate (AcOEt)), subfractions (polar (Pol) and nonpolar (Nonpol)), or isolated compounds (dihydrocorynantheol (DHC) and beta-sitosterol (ß-Sit)) isolated from CHE upon leukocytes, exudate, myeloperoxidase (MPO) adenosine-deaminase (ADA), nitrate/nitrite (NO(x)), interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and inhibitory kappa-B-alpha (IκB-α) degradation were evaluated. The CHE, Alk, Pol, Nonpol, DHC and ß-Sit, inhibited leukocytes, exudate, MPO and ADA, NO(x), IL-1ß, and TNF-α (P<0.05). The Hex and AcOEt fractions inhibited all of the proinflammatory parameters, except the exudate. The compound DHC prevented the IκB-α degradation. CONCLUSION: E. leiocarpa possesses important anti-inflammatory properties. These inhibitory effects occurred along with the downregulation of nitric oxide, IL-1ß and TNF-α levels. The isolated compounds DHC and ß-Sit may be partially responsible for these anti-inflammatory effects.

Asunto(s)

Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , Magnoliopsida/química , Corteza de la Planta/química , Extractos Vegetales/uso terapéutico , Adenosina Desaminasa , Alcaloides/análisis , Animales , Carragenina/farmacología , Citocinas/biosíntesis , Citocinas/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Inflamación/inducido químicamente , Leucocitos/efectos de los fármacos , Ratones , Sitoesteroles/análisis , Resultado del Tratamiento

RESUMEN

OBJECTIVES: The aim of this study was to investigate the anti-inflammatory effects of the crude hydroalcoholic extract (CHE) isolated from Esenbeckia leiocarpa Engl., and fractions and subfractions derived from it. METHODS: Dried E. leiocarpa Engl. bark was macerated and extracted with ethanol to obtain the CHE. The n-hexane, ethyl acetate, aqueous and alkaloid fractions, as well as two alkaloid subfractions (polar and nonpolar) were obtained from the CHE. A preliminary analysis using thin-layer chromatography was performed. Capillary electrophoresis, physical characteristics and spectral data produced by IR analysis and nuclear magnetic resonance (¹H and ¹³C NMR), and mass spectrometry analysis were used to identify and elucidate the structure of the major compounds. Swiss mice were used in a carrageenan-induced pleurisy model. Pro-inflammatory parameters (leukocyte and exudate concentrations, myeloperoxidase and adenosine-deaminase activity, and nitrate/nitrite, interleukin 1ß and tumour necrosis factor α levels) were quantified in exudates at 4 h after carrageenan-induced pleurisy in mice. KEY FINDINGS: The dihydrocorynantheol alkaloid was isolated as the majority compound in the CHE, ethyl acetate and alkaloid fractions, and in the polar and nonpolar alkaloid subfractions. The CHE, fractions and subfractions inhibited the increases in leukocyte and exudate concentrations, myeloperoxidase and adenosine-deaminase activity, and nitrite/nitrate, interleukin 1ß, and tumour necrosis factor α levels (P<0.05) in the fluid secreted from the pleural cavity of the carrageenan-treated mice. CONCLUSIONS: E. leiocarpa Engl. showed significant in vivo anti-inflammatory action by inhibiting the inflammation caused by carrageenan. This effect may be, in part, due to the dihydrocorynantheol alkaloid, which was identified as the majority compound isolated from E. leiocarpa bark.

Asunto(s)

Alcaloides/uso terapéutico , Antiinflamatorios/uso terapéutico , Inflamación/tratamiento farmacológico , Fitoterapia , Extractos Vegetales/uso terapéutico , Pleuresia/tratamiento farmacológico , Rutaceae/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Carragenina , Modelos Animales de Enfermedad , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Ratones , Corteza de la Planta , Extractos Vegetales/química , Extractos Vegetales/farmacología , Pleuresia/inducido químicamente , Pleuresia/metabolismo

RESUMEN

OBJECTIVE: Flavonoids are naturally occurring compounds widely distributed in plants, which have hypoglycemic potential and have been described as glucosidase inhibitors. This study evaluated the effect of flavonoids on intestinal glucosidase activity after in vivo and in vitro treatment. METHODS: For the in vivo studies animals received quercetin by gavage and for the in vitro assays a segment of the small intestine was used. To obtain the oral glucose tolerance curve fasted normal rats were loaded with glucose plus flavonoids. The glycemia was measured by the glucose oxidase method. RESULTS: Quercetin reduced the effect of sucrase and maltase in the in vivo and in vitro treatments. It was observed in the in vitro studies that the maximum inhibitory effect of kaempferitrin was around 23% for maltase activity. Also, for the sucrose substrate the specific enzyme activity was significantly decreased. Aglycone, flavonoids, and kaempferol decreased significantly the maltase activity at all concentrations assayed. Finally, rutin reduced maltase-specific activity at all concentrations studied. According to the oral glucose tolerance curve, rutin reduced the serum glucose levels at 15, 30, and 60 min when administered by oral gavage 30 min before glucose overload in rats. CONCLUSION: Based on these results, we can conclude that disaccharidases are targets of flavonoids in the regulation of glucose absorption and consequently glucose homeostasis.

Asunto(s)

Antioxidantes/farmacología , Glucosa/metabolismo , Inhibidores de Glicósido Hidrolasas , Homeostasis/efectos de los fármacos , Quempferoles/farmacología , Quercetina/farmacología , Animales , Glucemia/análisis , Disacaridasas/metabolismo , Inhibidores Enzimáticos/farmacología , Ayuno , Prueba de Tolerancia a la Glucosa , Intestino Delgado/efectos de los fármacos , Intestino Delgado/enzimología , Masculino , Ratas , Ratas Wistar , Sacarasa/metabolismo

RESUMEN

Fracionamento cromatográfico da fração em diclorometano obtida do extrato etanólico das folhas de Vernonia tweediana Baker (Asteraceae) conduziu ao isolamento de α-amirina, β-amirina, lupeol, β-sitosterol, estigmasterol e espinasterol. As estruturas foram identificadas através de técnicas espectroscópicas usuais, além da comparação com dados relatados na literatura. Os compostos isolados são relatados pela primeira vez para a espécie V. tweediana.

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Fractionation of the dichloromethane -soluble fraction from the ethanol extract of the leaves of Vernonia tweediana (Asteraceae) led to the isolation of α-amyrin, β-amyrin, lupeol, β-sitosterol, stigmasterol and spinasterol. The structures of the isolates were elucidated by spectroscopic analysis and comparison with literature data. The isolated compounds are reported for the first time to the species V. tweediana.