RESUMEN
BACKGROUND: Metabolic syndrome such as dyslipidemia, hypertension, obesity, impaired glucose tolerance and fatty liver, can be caused by modification of diet by means of overconsumption of high fructose diet. This study was designed to investigate whether combination with Red ginseng and Polygoni Multiflori Radix (RGPM), widely used traditional herbal medicine, ameliorates on highfructose (HF) diet-induced metabolic syndrome. METHODS: SD rats were fed the 60% HF diet with/without rosiglitazone, and RGPM 100, 300 mg/kg/day, respectively. All groups received regular diet or HF diet, respectively, for 8 weeks. The last three groups treatment of rosiglitazone and RPGM orally for a period of 6 weeks. RESULTS: Chronic treatment with RGPM significantly decreased body weight, fat weight and adipocyte size. RGPM significantly prevented the development of the metabolic disturbances such as hypertension, hyperlipidemia and impaired glucose tolerance. RGPM also led to increase in high density lipoprotein level in the HF group. RGPM suppressed high-fructose diet induced vascular inflammation marker expression such as adhesion molecules and ET-1 in aorta as well as increasing of C-reactive protein (CRP) levels in plasma. Similarly, RGPM attenuated hepatic lipid accumulation by inhibition of monocyte chemoattractant protein-1 (MCP-1) expression. CONCLUSION: An administration of RGPM may be a beneficial therapy for the treatment of metabolic syndrome through the improvement of hypertension, obesity, hyperlipidemia, vascular inflammation and insulin resistance.
Asunto(s)
Medicamentos Herbarios Chinos/uso terapéutico , Fructosa/administración & dosificación , Síndrome Metabólico/tratamiento farmacológico , Obesidad/tratamiento farmacológico , Panax , Fitoterapia , Polygonum , Tejido Adiposo/metabolismo , Animales , Glucemia/metabolismo , Presión Sanguínea , Composición Corporal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Proteína C-Reactiva/metabolismo , Quimiocina CCL2/sangre , Dieta/efectos adversos , Quimioterapia Combinada , Medicamentos Herbarios Chinos/farmacología , Fructosa/efectos adversos , Mediadores de Inflamación/metabolismo , Lipoproteínas HDL/sangre , Masculino , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Obesidad/complicaciones , Obesidad/metabolismo , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Gal-geun-dang-gwi-tang (GGDGT), an herbal medicine, is used to treat hypertension, stroke, and other inflammatory disorders in the clinical setting. Recently, GGDGT was recognized by the Korea Institute of Oriental Medicine. This study aimed to evaluate the effects of GGDGT in a diabetic atherosclerosis model using apolipoprotein E knockout (ApoE-/-) mice fed a Western diet. METHODS: The mice were divided into four groups: control group, C57BL6J mice receiving a regular diet (RD); ApoE-/- group, ApoE-/- mice receiving a Western diet (WD); rosiglitazone group, ApoE-/- mice receiving rosiglitazone (WD + 10 mg · kg(-1) · day(-1)); GGDGT group, ApoE-/- mice receiving GGDGT (WD + 200 mg · kg(-1) · day(-1)). RESULTS: Treatment with GGDGT significantly improved glucose tolerance and plasma lipid levels. In addition, GGDGT ameliorated acetylcholine-induced vascular relaxation of the aortic rings. Immunohistochemical staining showed that GGDGT suppressed intercellular adhesion molecule (ICAM)-1 expression; however, expression of endothelial nitric oxide synthase (eNOS) and insulin receptor substrate (IRS)-1 were restored in the thoracic aorta and skeletal muscle, respectively. CONCLUSIONS: These findings suggest that GGDGT attenuates endothelial dysfunction via improvement of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signalling pathway and improves insulin sensitivity in diabetic atherosclerosis.
Asunto(s)
Apolipoproteínas E , Aterosclerosis/tratamiento farmacológico , Angiopatías Diabéticas/tratamiento farmacológico , Dieta Occidental , Endotelio Vascular/efectos de los fármacos , Fitoterapia , Extractos Vegetales/uso terapéutico , Animales , Aorta Torácica , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Aterosclerosis/genética , Aterosclerosis/metabolismo , Glucemia/metabolismo , GMP Cíclico/metabolismo , Angiopatías Diabéticas/metabolismo , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Insulina/sangre , Proteínas Sustrato del Receptor de Insulina/metabolismo , Resistencia a la Insulina , Lípidos/sangre , Masculino , Medicina Tradicional Coreana , Ratones Endogámicos C57BL , Ratones Noqueados , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Extractos Vegetales/farmacología , Vasodilatación/efectos de los fármacosRESUMEN
OBJECTIVE: Nephrotic syndrome, a kidney disease with a variety of causes, is mainly characterized by heavy proteinuria, hypoproteinemia, and ascites. This study was designed to evaluate the underlying mechanism of action of Plantago asiatica L. (PAL) in treating nephrotic syndrome induced by puromycin aminonucleoside. METHODS: PAL has been used in Asia as a traditional medicine and dietary health supplement. Sprague-Dawley (SD) rats were intravenously injected with puromycin aminonucleoside (75 mg/kg/day), then treated with either Losartan (30 mg/kg/day) or PAL (200 mg/kg/day) by oral gavage for seven days. RESULTS: PAL significantly decreased ascites, proteinuria level, and plasma lipid parameters. In addition, treatment with PAL attenuated histological damage and hypoalbuminemia. Treatment with PAL also restored podocin expression and reduced inflammation markers such as intracellular adhesion molecules (ICAM-1), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor alpha (TNF-α) and high-mobility group box-1 (HMGB1). Lower expression levels of the apoptosis markers Bax, caspase-3 and capase-9 were documented in SD rats receiving PAL. PAL also significantly decreased the phosphorylation levels of MAPKs such as ERK, JNK and p38. CONCLUSION: As a multifunctional agent, PAL has a renoprotective effect in nephrotic syndrome rat models. The anti-inflammatory and anti-apoptotic properties, along with reductions in hyperlipidemia and ascites, represent important therapeutic effects. These results indicate that Plantago asiatica is likely to be a promising agent in the treatment of nephrotic syndrome.
Asunto(s)
Apoptosis/efectos de los fármacos , Inflamación/prevención & control , Riñón/efectos de los fármacos , Síndrome Nefrótico/tratamiento farmacológico , Extractos Vegetales/farmacología , Plantago , Animales , Ascitis , Biomarcadores/sangre , Caspasa 3/sangre , Caspasa 9/sangre , Hipoalbuminemia/prevención & control , Inflamación/sangre , Péptidos y Proteínas de Señalización Intracelular/sangre , Riñón/metabolismo , Riñón/patología , Lípidos/sangre , Masculino , Proteínas de la Membrana/sangre , Proteínas Quinasas Activadas por Mitógenos/sangre , Síndrome Nefrótico/inducido químicamente , Síndrome Nefrótico/metabolismo , Síndrome Nefrótico/patología , Fitoterapia , Extractos Vegetales/uso terapéutico , Puromicina Aminonucleósido , Ratas Sprague-Dawley , Proteína X Asociada a bcl-2/sangreRESUMEN
Atherosclerosis, a chronic and progressive disease, is a leading cause of endothelial dysfunction, diabetes mellitus, hypertension, and hypercholesterolemia. Betulinic acid (BA), a pentacyclic triterpene, has been reported to have a variety of biological effects, including anti-inflammatory and immunomodulatory properties. This study was designed to determine whether BA could prevent atherosclerosis in diabetic apolipoprotein-E gene knockout (ApoE KO) mice. The mice were treated with BA for 12 weeks to examine its beneficial effects on atherosclerosis in ApoE KO mice. Male ApoE KO mice and age-matched control group mice (C57BL/6Jms) were used as experimental systems and their systolic blood pressure, insulin resistance, and vascular inflammation were measured. BA-treated ApoE KO mice showed lowered systolic blood pressure. The metabolic parameter showed that BA decreased blood urea nitrogen, triglyceride, and total cholesterol levels. Blood glucose, insulin, glucose tolerance results, and the homeostasis model assessment of insulin resistance (HOMA-IR) index were found to be better in BA-treated ApoE KO mice than untreated ApoE KO mice. Consistent with the change in lipid profiles, oil red O and H&E staining revealed that treatment with BA reduced atherosclerotic lesions such as roughened endothelial layers. BA ameliorated the reduction of endothelial nitric oxide synthase (eNOS) expression, leading to the inhibition of intracellular adhesion molecule 1 (ICAM-1) and endothelin 1 (ET-1) expression. These results suggest that BA may be useful in the treatment and prevention of early atherosclerosis via the attenuation of endothelial dysfunction in diabetic ApoE KO mice.
Asunto(s)
Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Aterosclerosis/complicaciones , Aterosclerosis/prevención & control , Diabetes Mellitus Experimental/complicaciones , Técnicas de Inactivación de Genes , Triterpenos/farmacología , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Aterosclerosis/genética , Aterosclerosis/metabolismo , Glucemia/metabolismo , Hiperlipidemias/complicaciones , Hipertensión/complicaciones , Resistencia a la Insulina , Masculino , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico/biosíntesis , Triterpenos Pentacíclicos , Ácido BetulínicoRESUMEN
Metabolic syndrome including obesity, dyslipidemia and hypertension is a cluster of risk factors of cardiovascular disease. Fermentation of medicinal herbs improves their pharmacological efficacy. Red ginseng (RG), a widely used traditional herbal medicine, was reported with anti-inflammatory and anti-oxidant activity. Aim in the present study was to investigate that the effects of fermented red ginseng (FRG) on a high-fructose (HF) diet induced metabolic disorders, and those effects were compared to RG and losartan. Animals were divided into four groups: a control group fed a regular diet and tap water, and fructose groups that were fed a 60% high-fructose (HF) diet with/without RG 250 mg/kg/day or FRG 250 mg/kg/day for eight weeks, respectively. Treatment with FRG significantly suppressed the increments of body weight, liver weight, epididymal fat weight and adipocyte size. Moreover, FRG significantly prevented the development of metabolic disturbances such as hyperlipidemia and hypertension. Staining with Oil-red-o demonstrated a marked increase of hepatic accumulation of triglycerides, and this increase was prevented by FRG. FRG ameliorated endothelial dysfunction by downregulation of endothelin-1 (ET-1) and adhesion molecules in the aorta. In addition, FRG induced markedly upregulation of Insulin receptor substrate 1 (IRS-1) and glucose transporter type 4 (Glut4) in the muscle. These results indicate that FRG ameliorates obesity, dyslipidemia, hypertension and fatty liver in HF diet rats. More favorable pharmacological effects on HF diet induced metabolic disorders were observed with FRG, compared to an equal dose of RG. These results showed that the pharmacological activity of RG was enhanced by fermentation. Taken together, fermentated red ginseng might be a beneficial therapeutic approach for metabolic syndrome.
Asunto(s)
Fermentación , Síndrome Metabólico/tratamiento farmacológico , Panax/química , Fitoterapia , Preparaciones de Plantas/farmacología , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Glucemia/metabolismo , Presión Sanguínea/efectos de los fármacos , Peso Corporal , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Modelos Animales de Enfermedad , Regulación hacia Abajo , Endotelina-1/genética , Endotelina-1/metabolismo , Fructosa/administración & dosificación , Transportador de Glucosa de Tipo 4/genética , Transportador de Glucosa de Tipo 4/metabolismo , Proteínas Sustrato del Receptor de Insulina/genética , Proteínas Sustrato del Receptor de Insulina/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Losartán/farmacología , Síndrome Metabólico/inducido químicamente , Obesidad/tratamiento farmacológico , Tamaño de los Órganos/efectos de los fármacos , Ratas , Triglicéridos/sangre , Regulación hacia ArribaRESUMEN
Increased fructose ingestion has been linked to obesity, hyperglycemia, dyslipidemia, and hypertension associated with metabolic syndrome. Blackcurrant (Ribes nigrum; BC) is a horticultural crop in Europe. To induce metabolic syndrome, Sprague-Dawley rats were fed 60% high-fructose diet. Treatment with BC (100 or 300 mg/kg/day for 8 weeks) significantly suppressed increased liver weight, epididymal fat weight, C-reactive protein (CRP), total bilirubin, leptin, and insulin in rats with induced metabolic syndrome. BC markedly prevented increased adipocyte size and hepatic triglyceride accumulation in rats with induced metabolic syndrome. BC suppressed oral glucose tolerance and protein expression of insulin receptor substrate-1 (IRS-1) and phosphorylated AMP-activated protein kinase (p-AMPK) in muscle. BC significantly suppressed plasma total cholesterol, triglyceride, and LDL content. BC suppressed endothelial dysfunction by inducing downregulation of endothelin-1 and adhesion molecules in the aorta. Vascular relaxation of thoracic aortic rings by sodium nitroprusside and acetylcholine was improved by BC. The present study provides evidence of the potential protective effect of BC against metabolic syndrome by demonstrating improvements in dyslipidemia, hypertension, insulin resistance, and obesity in vivo.
RESUMEN
Overconsumption of fructose results in dyslipidemia, hypertension, and impaired glucose tolerance, which have documented correlation with metabolic syndrome. Gastrodia elata, a widely used traditional herbal medicine, was reported with anti-inflammatory and antidiabetes activities. Thus, this study examined whether ethanol extract of Gastrodia elata Blume (EGB) attenuate lipid metabolism and endothelial dysfunction in a high-fructose (HF) diet animal model. Rats were fed the 65% HF diet with/without EGB 100 mg/kg/day for 8 weeks. Treatment with EGB significantly suppressed the increments of epididymal fat weight, blood pressure, plasma triglyceride, total cholesterol levels, and oral glucose tolerance, respectively. In addition, EGB markedly prevented increase of adipocyte size and hepatic accumulation of triglycerides. EGB ameliorated endothelial dysfunction by downregulation of endothelin-1 (ET-1) and adhesion molecules in the aorta. Moreover, EGB significantly recovered the impairment of vasorelaxation to acetylcholine and levels of endothelial nitric oxide synthase (eNOS) expression and induced markedly upregulation of phosphorylation AMP-activated protein kinase (AMPK) α in the liver, muscle, and fat. These results indicate that EGB ameliorates dyslipidemia, hypertension, and insulin resistance as well as impaired vascular endothelial function in HF diet rats. Taken together, EGB may be a beneficial therapeutic approach for metabolic syndrome.