RESUMEN

For over 4000 years, liquorice has been one of the most frequently employed botanicals as a traditional herbal medicine. Although previous reports have found that liquorice flavonoids possess various health beneficial effects, the underlying mechanism responsible for the anti-diabetic effect of liquorice flavonoids remains unclear. The present study demonstrates that liquorice flavonoid oil (LFO) improves type 2 diabetes mellitus through GLUT4 translocation to the plasma membrane by activating both the adenosine monophosphate-activated protein kinase (AMPK) pathway and Akt pathway in muscle of KK-Ay mice. Furthermore, LFO lowered postprandial hyperglycaemia in a human study. These results indicate that LFO may exert a therapeutic effect on metabolic disorders, such as diabetes and hyperglycaemia, by modulating glucose metabolism through AMPK- and insulin-dependent pathways in skeletal muscle.

Asunto(s)

Flavonoides/farmacología , Transportador de Glucosa de Tipo 4/metabolismo , Glycyrrhiza/química , Hiperglucemia/prevención & control , Hipoglucemiantes/farmacología , Músculo Esquelético/metabolismo , Aceites de Plantas/farmacología , Adenilato Quinasa/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Membrana Celular/metabolismo , Diabetes Mellitus Tipo 2/prevención & control , Dieta Alta en Grasa , Humanos , Insulina/sangre , Masculino , Ratones , Músculo Esquelético/enzimología , Tamaño de los Órganos/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo

RESUMEN

AIMS: Muscle mass is regulated by the balance between the synthesis and degradation of muscle proteins. Loss of skeletal muscle mass is associated with an increased risk of developing metabolic diseases such as obesity and type 2 diabetes mellitus. The aim of this study was to clarify the effects of licorice flavonoid oil on muscle mass in KK-Ay/Ta mice. MAIN METHODS: Male genetically type II diabetic KK-Ay/Ta mice received 0, 1, or 1.5 g/kg BW of licorice flavonoid oil by mouth once daily for 4 weeks. After 4 weeks, the femoral and soleus muscles were collected for western blotting for evaluation of the mTOR/p70 S6K, p38/FoxO3a, and Akt/FoxO3a signaling pathways. KEY FINDINGS: Ingestion of licorice flavonoid oil significantly enhanced femoral muscle mass without affecting body weight in KK-Ay/Ta mice. Licorice flavonoid oil also decreased expression of MuRF1 and atrogin-1, which are both markers of muscle atrophy. The mechanisms by which licorice flavonoid oil enhances muscle mass include activation of mTOR and p70 S6K, and regulation of phosphorylation of FoxO3a. SIGNIFICANCE: Ingestion of licorice flavonoids may help to prevent muscle atrophy.

Asunto(s)

Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Flavonoides/farmacología , Glycyrrhiza/química , Músculo Esquelético/efectos de los fármacos , Aceites de Plantas/farmacología , Animales , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/biosíntesis , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Proteína Forkhead Box O3/biosíntesis , Proteína Forkhead Box O3/genética , Péptidos y Proteínas de Señalización Intracelular , Masculino , Ratones , Proteínas Musculares/antagonistas & inhibidores , Proteínas Musculares/biosíntesis , Proteínas Musculares/genética , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/patología , Tamaño de los Órganos/efectos de los fármacos , Proteínas Ligasas SKP Cullina F-box/antagonistas & inhibidores , Proteínas Ligasas SKP Cullina F-box/biosíntesis , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/biosíntesis , Proteínas de Motivos Tripartitos , Proteínas Quinasas p38 Activadas por Mitógenos/biosíntesis

RESUMEN

The biological effects of heat-killed Pediococcus acidilactici R037 (R037) were evaluated when orally administered in mice and rats. Oral R037 administration at a daily dose of 10 and 100 mg/kg for 3 wk dose-dependently reduced fasting and non-fasting serum triglyceride concentrations in KK-Ay/TaJcl mice, a model of type II diabetes, obesity, hypercholesterolemia, and hypertriglyceridemia. Serum levels of free fatty acids in the 100 mg/kg group tended to decrease (not statistically significant), and total cholesterol levels remained unchanged. Treatment with R037 resulted in a significant decrease in blood glucose (at 100 mg/kg) and liver weight (at 10 and 100 mg/kg), and a small body weight gain (at 100 mg/kg) as compared to those in control mice. In addition, oral R037 administration at 100, 200, and 400 mg/kg/d for 1 wk dose-dependently suppressed the increase in serum triglyceride levels in Wistar rats after oral fat loading. Moreover, intraduodenal injection of 120 mg of R037 in Wistar rats suppressed gastric vagal nerve activity (GVNA) indicating suppression of intestinal digestion and absorption of food, and suppression of appetite. The R037 injection potentiated epididymal white adipose tissue sympathetic nerve activity (WAT-SNA) and tended to potentiate pancreatic sympathetic nerve activity (PSNA), suggesting that R037 activated lipolysis. Taken together, these findings indicate that R037 lowers serum triglycerides, possibly through suppressing intestinal absorption and potentiating lipolytic pathways. R037 may be useful for primary prevention of coronary artery diseases in subjects with mild or borderline dyslipidemia in combination with lifestyle changes.

Asunto(s)

Pediococcus acidilactici , Probióticos , Triglicéridos/sangre , Tejido Adiposo Blanco/metabolismo , Administración Oral , Animales , Apetito , Glucemia/metabolismo , Ácidos Grasos no Esterificados/sangre , Mucosa Gástrica/metabolismo , Microbioma Gastrointestinal , Absorción Intestinal , Lipólisis , Hígado/metabolismo , Masculino , Ratones , Ratas , Estómago/microbiología , Sistema Nervioso Simpático/metabolismo , Aumento de Peso

RESUMEN

Licorice flavonoid oil (LFO) is a new functional food ingredient consisting of hydrophobic licorice polyphenols in medium-chain triglycerides. Recent studies reported that LFO prevented and ameliorated diet-induced obesity via the regulation of lipid metabolism-related gene expression in the livers of mice and rats, while it reduced body weight in overweight human subjects by reducing total body fat. However, the direct effects of LFO on energy metabolism have not been studied in human subjects. Therefore, we investigated the effects of ingestion of LFO on energy metabolism, including fat oxidation, by measuring body surface temperature under resting conditions and respiratory gas analysis under exercise conditions in healthy humans. We showed that ingestion of a single 600 mg dose of LFO elevated body trunk skin temperature when measured in a slightly cooled air-conditioned room, and increased oxygen consumption and decreased the respiratory exchange ratio as measured by respiratory gas analysis during 40% Vo2max exercise with a cycle ergometer. Furthermore, repeated ingestion of 300 mg of LFO for 8 d decreased respiratory exchange during the recovery period following 40 min of 30% Vo2max exercise on a treadmill. These results suggest that LFO enhances fat oxidation in humans during light exercise.

Asunto(s)

Ejercicio Físico , Flavonoides/farmacología , Glycyrrhiza/química , Metabolismo de los Lípidos/efectos de los fármacos , Aceites de Plantas/farmacología , Polifenoles/farmacología , Tejido Adiposo/metabolismo , Adolescente , Adulto , Pueblo Asiatico , Índice de Masa Corporal , Peso Corporal/efectos de los fármacos , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Alimentos Funcionales , Humanos , Japón , Hígado/efectos de los fármacos , Hígado/metabolismo , Obesidad/tratamiento farmacológico , Consumo de Oxígeno , Triglicéridos/sangre , Adulto Joven

RESUMEN

The present study demonstrates that glabridin, a prenylated isoflavone in licorice, stimulates glucose uptake through the adenosine monophosphate-activated protein kinase (AMPK) pathway in L6 myotubes. Treatment with glabridin for 4h induced glucose uptake in a dose-dependent manner accompanied by the translocation of glucose transporter type 4 (GLUT4) to the plasma membrane. Glabridin needed at least 4h to increase glucose uptake, while it significantly decreased glycogen and increased lactic acid within 15 min. Pharmacological inhibition of AMPK by Compound C suppressed the glabridin-induced glucose uptake, whereas phosphoinositide 3-kinase and Akt inhibition by LY294002 and Akt1/2 inhibitor, respectively, did not. Furthermore, glabridin induced AMPK phosphorylation, and siRNA for AMPK completely abolished glabridin-induced glucose uptake. We confirmed that glabridin-rich licorice extract prevent glucose intolerance accompanied by the AMPK-dependent GLUT4 translocation in the plasma membrane of mice skeletal muscle. These results indicate that glabridin may possess a therapeutic effect on metabolic disorders, such as diabetes and hyperglycemia, by modulating glucose metabolism through AMPK in skeletal muscle cells.

Asunto(s)

Proteínas Quinasas Activadas por AMP/metabolismo , Glucosa/metabolismo , Isoflavonas/farmacología , Células Musculares/efectos de los fármacos , Células Musculares/metabolismo , Fenoles/farmacología , Animales , Transporte Biológico/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Masculino , Ratones , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de Señal/efectos de los fármacos

RESUMEN

Licorice flavonoid oil (LFO) is a new functional food ingredient consisting of hydrophobic licorice polyphenols in medium-chain triglycerides. Recently, it was reported that licorice and its derivatives have anticarcinogenic activity in some types of tumors. However, the anticarcinogenic activity has not been identified in the liver, which is a major target organ for carcinogenesis in human. Therefore, we hypothesized that LFO has antihepatocarcinogenic activity, and we tested this hypothesis using the rat medium-term liver bioassay for carcinogens. Six-week-old male F344 rats (15 animals/group) received N-diethylnitrosamine (200 mg/kg by intraperitoneal injection) to initiate carcinogenesis. From the second week after initiation, animals received a 6-week regimen of either LFO concentrate solution (0, 150, 300, or 600 mg/kg) intragastrically or phenobarbital sodium salt in the diet (500 ppm) as a positive control. During the third week after initiation, animals were subjected to a two-thirds partial hepatectomy. During the eighth week of the treatment period, liver samples were taken from animals and examined immunohistochemically for expression of glutathione S-transferase placental form. No increase in the number of glutathione S-transferase placental form-positive liver foci was observed in all LFO groups compared with the negative control (solvent) group, and the number of foci in the 600 mg/kg LFO group was significantly lower than that in the negative control group. These results indicate that LFO concentrate solution has a significant inhibitory effect on liver carcinogenesis at 600 mg/kg.

Asunto(s)

Antineoplásicos Fitogénicos/uso terapéutico , Flavonoides/uso terapéutico , Glutatión Transferasa/metabolismo , Glycyrrhiza/química , Neoplasias Hepáticas/prevención & control , Hígado/metabolismo , Preparaciones de Plantas/uso terapéutico , Animales , Antineoplásicos Fitogénicos/farmacología , Dietilnitrosamina , Flavonoides/farmacología , Alimentos Funcionales , Masculino , Fenobarbital , Fenoles/farmacología , Fenoles/uso terapéutico , Fitoterapia , Preparaciones de Plantas/farmacología , Ratas , Ratas Endogámicas F344 , Triglicéridos

RESUMEN

OBJECTIVES: To evaluate effects of licorice flavonoid oil (LFO) on total body fat and visceral fat together with body weight, body mass index (BMI) and safety parameters in overweight subjects. METHODS: In this randomized, double-blind, placebo-controlled study, moderately overweight participants (56 males, 28 females, BMI 24-30 kg/m(2)) were assigned to four groups receiving a daily dose of either 0 (placebo), 300, 600, or 900 mg of LFO. Total body fat mass was measured by dual-energy X-ray absorptiometry (DXA) and visceral fat area by abdominal computed tomography (CT) scan at baseline and after 8 weeks of LFO ingestion. Body weight, BMI, and blood samples were examined at baseline and after 4 and 8 weeks of LFO ingestion. RESULTS: Although caloric intake was similar in all four groups, total body fat mass decreased significantly in the three LFO groups after 8 weeks of ingestion. LFO (900 mg/day) resulted in significant decreases from baseline levels in visceral fat area, body weight, BMI, and LDL-cholesterol. No significant adverse effects were observed.

RESUMEN

OBJECTIVE: Licorice flavonoids have various physiological activities such as abdominal fat-lowering, hypoglycemic and antioxidant effects. Licorice flavonoid oil (LFO: Kaneka Glavonoid Rich Oil) is a new dietary ingredient containing licorice flavonoids dissolved in medium-chain triglycerides (MCT). Glabridin is one of the bioactive flavonoids included specifically in licorice Glycyrrhiza glabra L. and is the most abundant flavonoid in LFO. In this study, we assessed the safety of LFO in healthy humans and determined the plasma concentration profile of glabridin as a marker compound. METHODS: A single-dose and two multiple-dose studies at low (300 mg), moderate (600 mg) and high (1200 mg) daily doses of LFO were carried out using a placebo-controlled single-blind design. In each study the safety of LFO and the pharmacokinetics of glabridin were assessed. RESULTS: Pharmacokinetic analysis in the single-dose study with healthy male subjects (n = 5) showed that glabridin was absorbed and reached the maximum concentration (Cmax) after approximately 4 h (Tmax), and then eliminated relatively slowly in a single phase with a T1/2 of approximately 10 h at all doses. The Cmax and AUC(0-24 h) increased almost linearly with dose. The multiple-dose studies with healthy male and female subjects for 1 week and 4 weeks suggested that plasma glabridin reached steady state levels within 2 weeks with a single daily administration of 300 to 1200 mg/day LFO. In these human studies at three dose levels, there were no clinically noteworthy changes in hematological or related biochemical parameters. All clinical events observed were mild and considered to be unrelated to LFO administration even after repeated administration for 4 weeks. CONCLUSION: These studies demonstrated that LFO is safe when administered once daily up to 1200 mg/day. This is the first report on the safety of licorice flavonoids in an oil preparation and the first report on the pharmacokinetics of glabridin in human subjects.

Asunto(s)

Flavonoides/farmacocinética , Glycyrrhiza/química , Fenoles/farmacocinética , Adulto , Antioxidantes , Área Bajo la Curva , Biomarcadores/sangre , Relación Dosis-Respuesta a Droga , Femenino , Flavonoides/efectos adversos , Flavonoides/sangre , Humanos , Isoflavonas , Masculino , Persona de Mediana Edad , Fenoles/efectos adversos , Fenoles/sangre , Aceites de Plantas/química , Seguridad , Método Simple Ciego

RESUMEN

We applied licorice flavonoid oil (LFO) to high-fat diet-induced obese C57BL/6J mice and investigated its effect. LFO contains hydrophobic flavonoids obtained from licorice by extraction with ethanol. The oil is a mixture of medium-chain triglycerides, having glabridin, a major flavonoid of licorice, concentrated to 1.2% (w/w). Obese mice were fed on a high-fat diet containing LFO at 0 (control), 0.5%, 1.0%, or 2.0% for 8 weeks. Compared with mice in the control group, those in the 1% and 2% LFO groups efficiently reduced the weight of abdominal white adipose tissues and body weight gain. A histological examination revealed that the adipocytes became smaller and the fatty degenerative state of the hepatocytes was improved in the 2% LFO group. A DNA microarray analysis of the liver showed up-regulation of those genes for beta-oxidation and down-regulation of those for fatty acid synthesis in the 2% LFO group. These findings suggest that LFO prevented and ameliorated diet-induced obesity via the regulation of lipid metabolism-related gene expression in the liver.

Asunto(s)

Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Peso Corporal/efectos de los fármacos , Flavonoides/farmacología , Glycyrrhiza/química , Obesidad/tratamiento farmacológico , Adipocitos Blancos/efectos de los fármacos , Alimentación Animal , Animales , Regulación hacia Abajo/efectos de los fármacos , Femenino , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratones , Ratones Endogámicos C57BL , Obesidad/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Reacción en Cadena de la Polimerasa , Regulación hacia Arriba/efectos de los fármacos

RESUMEN

Glabridin is a major flavonoid included specifically in licorice (Glycyrrhiza glabra L.), and has various physiological activities including antioxidant and anti-inflammatory effects. We have developed and validated an analytical method for determination of glabridin in human plasma by solid-phase extraction (SPE) and LC-MS/MS. Glabridin was extracted from plasma by SPE using a C8 cartridge and analyzed by LC-MS/MS using mefenamic acid as an internal standard (IS). The analyte were separated by a C18 column on LC, and monitored with a fragment ion of m/z 201 formed from a molecular ion of m/z 323 for glabridin and that of m/z 196 from m/z 240 for IS during negative ion mode with tandem MS detection. The lower limit of quantitation (LLOQ) of glabridin was 0.1 ng/mL in plasma, corresponding to 1.25 pg injected on-column. The calibration curves exhibited excellent linearity (r>0.997) between 0.1 and 50 ng/mL. Precision and accuracy were <17 and <+/-7% at LLOQ, and <11 and <+/-5% at other concentrations. Glabridin was recovered >90%, and was stable when kept at 10 degrees C for 72 h, at -20 degrees C until 12 weeks, and after three freeze-thaw cycles. This is the first report on determination of glabridin in body fluids by the selective, sensitive, and reproducible method.

Asunto(s)

Cromatografía Liquida/métodos , Fenoles/análisis , Fenoles/sangre , Espectrometría de Masa por Ionización de Electrospray/métodos , Humanos , Isoflavonas , Espectrometría de Masas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad

RESUMEN

The turmeric (Curcuma longa L. rhizomes) EtOH extract significantly suppressed an increase in blood glucose level in type 2 diabetic KK-A(y) mice. In an in vitro evaluation, the extract stimulated human adipocyte differentiation in a dose-dependent manner and showed human peroxisome proliferator-activated receptor (PPAR)-gamma ligand-binding activity in a GAL4-PPAR-gamma chimera assay. The main constituents of the extract were identified as curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone, which had also PPAR-gamma ligand-binding activity. These results indicate that turmeric is a promising ingredient of functional food for the prevention and/or amelioration of type 2 diabetes and that curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone mainly contribute to the effects via PPAR-gamma activation.

Asunto(s)

Curcuma , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/genética , Hipoglucemiantes/uso terapéutico , Rizoma , Animales , Relación Dosis-Respuesta a Droga , Femenino , Hipoglucemiantes/química , Hipoglucemiantes/aislamiento & purificación , Ratones

RESUMEN

Turmeric, the rhizome of Curcuma longa L., has a wide range of effects on human health. The chemistry includes curcuminoids and sesquiterpenoids as components, which are known to have antioxidative, anticarcinogenic, and antiinflammatory activities. In this study, we investigated the effects of three turmeric extracts on blood glucose levels in type 2 diabetic KK-A(y) mice (6 weeks old, n = 5/group). These turmeric extracts were obtained by ethanol extraction (E-ext) to yield both curcuminoids and sesquiterpenoids, hexane extraction (H-ext) to yield sesquiterpenoids, and ethanol extraction from hexane-extraction residue (HE-ext) to yield curcuminoids. The control group was fed a basal diet, while the other groups were fed a diet containing 0.1 or 0.5 g of H-ext or HE-ext/100 g of diet or 0.2 or 1.0 g of E-ext/100 g of diet for 4 weeks. Although blood glucose levels in the control group significantly increased (P < 0.01) after 4 weeks, feeding of 0.2 or 1.0 g of E-ext, 0.5 g of H-ext, and 0.5 g of HE-ext/100 g of diet suppressed the significant increase in blood glucose levels. Furthermore, E-ext stimulated human adipocyte differentiation, and these turmeric extracts had human peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand-binding activity in a GAL4-PPAR-gamma chimera assay. Also, curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone had PPAR-gamma ligand-binding activity. These results indicate that both curcuminoids and sesquiterpenoids in turmeric exhibit hypoglycemic effects via PPAR-gamma activation as one of the mechanisms, and suggest that E-ext including curcuminoids and sesquiterpenoids has the additive or synergistic effects of both components.

Asunto(s)

Glucemia/análisis , Curcuma/química , Curcumina/análisis , Diabetes Mellitus Tipo 2/sangre , Hipoglucemiantes/análisis , Sesquiterpenos/análisis , Adipocitos/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , Curcumina/administración & dosificación , Diabetes Mellitus Tipo 2/terapia , Etanol , Humanos , Hipoglucemiantes/administración & dosificación , Ratones , PPAR gamma/metabolismo , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Sesquiterpenos/administración & dosificación

RESUMEN

Licorice, the root of the Glycyrrhiza species, is one of the most frequently employed botanicals in traditional medicines. In this study, we investigated the effects of hydrophobic flavonoids from Glycyrrhiza glabra LINNE on abdominal fat accumulation and blood glucose level in obese diabetic KK-A(y) mice. In order to enrich a fraction of hydrophobic flavonoids, licorice flavonoid oil (LFO) was prepared by further extracting licorice ethanolic extract with medium-chain triglycerides (MCT), and adjusting the concentration of glabridin, the major flavonoid of licorice, to 1.2% in oil. KK-A(y) mice aged 6 weeks were assigned to 5 groups (n=6 each), and fed a high-fat diet containing 0 (control), 0.5%, 1%, or 2% LFO, or 0.5% conjugated linoleic acid (CLA) for 4 weeks. Compared with the control, body weight gain and weights of abdominal adipose tissues were suppressed (p<0.05) by feeding the diet containing 2% LFO, and blood glucose levels after 2 and 4 weeks were suppressed by all of the diets containing LFO. Although CLA feeding suppressed (p<0.05) body weight gain, it increased (p<0.05) blood glucose level after 2 weeks compared with the control level. Furthermore, LFO and licorice ethanolic extract stimulated human adipocyte differentiation in vitro. These results indicate that licorice hydrophobic flavonoids have abdominal fat-lowering and hypoglycemic effects, possibly mediated via activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma).

Asunto(s)

Tejido Adiposo/efectos de los fármacos , Fármacos Antiobesidad/farmacología , Glucemia/efectos de los fármacos , Flavonoides/farmacología , Glycyrrhiza , Hipoglucemiantes/farmacología , Abdomen , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Tejido Adiposo/metabolismo , Animales , Diferenciación Celular/efectos de los fármacos , Femenino , Glycyrrhiza/química , Ratones , Ratones Obesos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Raíces de Plantas/química

RESUMEN

The EtOAc extract of licorice (Glycyrrhiza uralensis roots) exhibited considerable PPAR-gamma ligand-binding activity. Bioassay-guided fractionation of the extract using a GAL-4-PPAR-gamma chimera assay method resulted in the isolation of two isoflavenes, one of which is a new compound named dehydroglyasperin D, an isoflavan, two 3-arylcoumarins, and an isoflavanone as the PPAR-gamma ligand-binding active ingredients of licorice. The isoprenyl group at C-6 and the C-2' hydroxyl group in the aromatic ring-C part in the isoflavan, isoflavene, or arylcoumarin skeleton were found to be the structural requirements for PPAR-gamma ligand-binding activity. Glycyrin, one of the main PPAR-gamma ligands of licorice, significantly decreased the blood glucose levels of genetically diabetic KK-A(y) mice.

Asunto(s)

Cumarinas/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Glycyrrhiza , Hipoglucemiantes/uso terapéutico , Fenoles/farmacología , Fitoterapia , Extractos Vegetales/farmacología , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Transcripción/metabolismo , Animales , Sitios de Unión , Línea Celular , Chlorocebus aethiops , Ligandos , Ratones , Ratones Mutantes , Fenoles/farmacocinética , Fenoles/uso terapéutico , Pioglitazona , Extractos Vegetales/farmacocinética , Extractos Vegetales/uso terapéutico , Receptores Citoplasmáticos y Nucleares/genética , Proteínas Recombinantes de Fusión/metabolismo , Relación Estructura-Actividad , Tiazolidinedionas/uso terapéutico , Factores de Transcripción/genética

RESUMEN

The metabolic syndrome, including type 2 diabetes, insulin resistance, obesity/abdominal obesity, hypertension and dyslipidemia, is a major public health problem. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands such as thiazolidinediones are effective against this syndrome. In this study, we showed that nonaqueous fractions of licorice (Glycyrrhiza uralensis Fisher) extracted with ethanol, ethyl acetate and acetone, but not an aqueous extract, had PPAR-gamma ligand-binding activity with a GAL4-PPAR-gamma chimera assay. Some prenylflavonoids including glycycoumarin, glycyrin, dehydroglyasperin C and dehydroglyasperin D, a newly found compound, were identified as active compounds with PPAR-gamma ligand-binding activity in the nonaqueous fraction of licorice. A licorice ethanolic extract contained these four active compounds at a total concentration of 16.7 g/100 g extract. Feeding the licorice ethanolic extract at 0.1-0.3 g/100 g diet [approximately 100 to 300 mg/(kg body x d)] for 4 wk decreased (P < 0.05) blood glucose level in younger (6 wk old) and older (13 wk old) diabetic KK-Ay mice and reduced (P < 0.05) weights of intra-abdominal adipose tissues in high fat diet-induced obese C57BL mice. An increase in blood pressure in spontaneously hypertensive rats was suppressed (P < 0.01) by 3 wk of oral administration of the licorice ethanolic extract at 300 mg/(kg body x d). These findings indicate that licorice ethanolic extract is effective in preventing and ameliorating diabetes, ameliorating abdominal obesity and preventing hypertension, and suggest that licorice ethanolic extract would be effective in preventing and/or ameliorating the metabolic syndrome.

Asunto(s)

Diabetes Mellitus Tipo 2/tratamiento farmacológico , Glycyrrhiza , Extractos Vegetales/farmacología , Receptores Citoplasmáticos y Nucleares/fisiología , Tiazolidinedionas/farmacología , Factores de Transcripción/fisiología , Acetatos , Acetona , Animales , Glucemia/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Línea Celular , Chlorocebus aethiops , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/prevención & control , Grasas de la Dieta , Etanol , Femenino , Flavonoides/farmacología , Ligandos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/prevención & control , Raíces de Plantas , Plásmidos , Ratas , Ratas Endogámicas SHR , Receptores Citoplasmáticos y Nucleares/efectos de los fármacos , Proteínas Recombinantes de Fusión/efectos de los fármacos , Factores de Transcripción/efectos de los fármacos , Transfección