RESUMEN

As a continuation of our research on the Baccharis genus, the evaluation of the antioxidant effect by TRAP and TBARS assays of three isolated compounds from n-butanol fractions of B. articulata and B. usterii is reported. The structures of these compounds were established as 4-O-beta-D-glucopyranosyl-3,5-dimethoxybenzyl-methanol (1), 5-O-[E]-dicaffeoylquinic acid (2), and 7-hydroxy-5,4'-dimethoxyflavone (3). In the TRAP assay it was possible to observe an antioxidant effect of both n-butanol fractions at 1.25 microg/mL. Among the isolated compounds, compound 2 displayed a remarkable contribution to the total antioxidant capacity of the n-butanol fraction of B. usterii. Moreover, the n-butanol fractions of both species, compounds 1 and 2 at 40.0 microg/mL were efficient in protection of lipid peroxidation in the TBARS experiment. They are promising lead compounds for use in medicinal chemistry studies.

Asunto(s)

Antioxidantes/farmacología , Baccharis/química , Fenoles/química , Fenoles/farmacología , Antioxidantes/química , Baccharis/clasificación , Sustancias Reactivas al Ácido Tiobarbitúrico/química

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

Rutin is a flavonoid with several pharmacological properties and it has been demonstrated that rutin can modulate glucose homeostasis. In skeletal muscle, an increase in intracellular calcium concentration may induce glucose transporter-4 (GLUT-4) translocation with consequent glucose uptake. The aim of this study was to investigate the effect of rutin and intracellular pathways on calcium uptake as well as the involvement of calcium in glucose uptake in skeletal muscle. The results show that rutin significantly stimulated calcium uptake through voltage-dependent calcium channels as well as mitogen-activated kinase (MEK) and protein kinase A (PKA) signaling pathways. Also, rutin stimulated glucose uptake in the soleus muscle and this effect was mediated by extracellular calcium and calcium-calmodulin-dependent protein kinase II (CaMKII) activation. In conclusion, rutin significantly stimulates calcium uptake in rat soleus muscles. Furthermore, the increase in intracellular calcium concentration is involved in DNA activation by rutin. Also, rutin-induced glucose uptake via CaMKII may result in GLUT-4 translocation to the plasma membrane, characterizing an insulin-independent pathway. These findings indicate that rutin is a potential drug candidate for diabetes therapy.

Asunto(s)

Canales de Calcio/metabolismo , Calcio/metabolismo , Glucosa/metabolismo , Músculo Esquelético/efectos de los fármacos , Rutina/farmacología , Animales , Antioxidantes/farmacología , Transporte Biológico/efectos de los fármacos , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , ADN/metabolismo , Masculino , Músculo Esquelético/metabolismo , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Timidina/metabolismo

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

CONTEXT: Cecropia glaziovii Snethl. (Cecropiaceae), commonly known as "embaúba-vermelha", is widely distributed throughout Latin America and has been reported in Brazilian folk medicine to treat cough, asthma, high blood pressure and inflammation. OBJECTIVE: Investigate the hepatoprotective properties of crude hydroethanolic extract of C. glaziovii as well as its in vitro antioxidant and antiviral (HSV-1 acyclovir resistant strain) activities. MATERIALS AND METHODS: The hepatoprotective effect, the antioxidant properties and antiviral activity of crude hydroethanol extract (RCE40) from C. glaziovii leaves were evaluated by carbon-tetrachloride (CCl(4))-induced hepatotoxicity, by TBARS (thiobarbituric acid reactive species) and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assays, respectively. RESULTS: The RCE40 extract (20 mg/kg) inhibited lipid peroxidation on liver in post injury treatment and decreased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, in this protocol the RCE40 (20 mg/kg) enhanced the activity of hepatic enzymes (SOD/CAT) which are involved in combating reactive oxygen species (ROS), suggesting that it possesses the capacity to attenuate the CCl(4)-induced liver damage. Moreover the RCE40 (20 mg/kg) inhibited TBARS formation induced by several different inductors of oxidative stress showing significant antioxidant activity, including physiologically relevant concentration, as low as 2 µg/mL. Concerning antiviral activity, the RCE40 was effective against herpes simplex virus type 1 replication (29R acyclovir resistant strain) with EC(50) = 40 µg/mL and selective index (SI) = 50. DISCUSSION AND CONCLUSION: These results indicate that C. glaziovii could be a good source of antioxidant and anti-HSV-1 lead compounds.

Asunto(s)

Aciclovir , Cecropia , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Farmacorresistencia Viral/efectos de los fármacos , Herpesvirus Humano 1/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Aciclovir/farmacología , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Chlorocebus aethiops , Farmacorresistencia Viral/fisiología , Herpesvirus Humano 1/fisiología , Masculino , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Hojas de la Planta , Ratas , Ratas Wistar , Células Vero

RESUMEN

There are many studies about the biological activities of Vitis vinifera grape seeds, which are rich in phenolic compounds, known by their several health beneficial effects. However, until now there is no data about biological activities of the seeds of V. labrusca, specie found in South and North America. Every year, the global wine production (around 260 million hL) generates about 19.5 million ton of wastes, which are usually discarded in the environment. The aim of this research was to evaluate the antioxidant and anti-inflammatory activities of aqueous extracts of seeds from wine wastes of Vitis labrusca (cv. 'Bordo' and 'Isabella'). Both extracts showed significant antioxidant and anti-inflammatory activities, which are positively correlated with total phenolic content, suggesting that these compounds might be the major contributors to the biological activity of these extracts. These results indicate that water extraction from winery wastes is an option to obtain phenolic compounds with antioxidant and anti-inflammatory activities helping to maintain environmental balance.

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Apesar de existirem vários estudos sobre a atividade biológica de sementes de uva de Vitis vinifera, ricas em compostos fenólicos com reconhecidos efeitos benéficos à saúde, não existem, até o momento, dados a respeito da atividade biológica de sementes de V. labrusca, espécie amplamente encontrada na América do Sul e do Norte. A cada ano, a produção mundial de vinho (cerca de 260 milhões de hL) gera, aproximadamente, 19,5 milhões de toneladas de resíduos, usualmente descartados no meio ambiente. Em vista disso, o objetivo deste estudo foi avaliar as atividades antioxidante e anti-inflamatória de extratos aquosos de sementes de resíduos de vinificação de V. labrusca (cv. 'Bordo' e 'Isabel'). Os resultados mostraram que ambos os extratos apresentam significante atividade antioxidante e anti-inflamatória, as quais apresentam correlação positiva com o conteúdo de compostos fenólicos dos extratos, sugerindo que estes podem contribuir, significativamente, para a atividade biológica observada. Estes resultados mostram que é possível obter compostos fenólicos com atividades antioxidante e anti-inflamatória utilizando extração aquosa, além de contribuir com o equilíbrio do meio ambiente.