RESUMEN
This study investigated the effect of aqueous extract of Cucurbita ficifolia Bouché on systemic chronic inflammation in an obesity model induced by monosodium glutamate (MSG) via modulating the expression of adipokines (TNF-α, IL-6, resistin, and adiponectin) and immune-regulatory cytokines (IFN-γ and IL-10). Cucurbita ficifolia extract was administered daily by gavage to lean and MSG-obese mice for 30 days. At the end of treatment, cytokine mRNA expression in adipose tissue was determined by real-time polymerase chain reaction (PCR), and the protein levels of these cytokines were also quantified by enzyme-linked immunosorbent assay (ELISA). Cucurbita ficifolia extract decreased body mass and inflammation in MSG-obese mice by reducing the expression of TNF-α and IL-6; these decreases were parallel to significant reductions in protein levels. The extract also increased protein levels of IL-10 in lean mice and IFN-γ in both lean and MSG-obese mice. In conclusion, C. ficifolia extract modulates systemic chronic inflammation in MSG-obese mice and could have a beneficial effect on the adaptive immune system in obesity.
Asunto(s)
Adipoquinas/biosíntesis , Cucurbita/química , Citocinas/biosíntesis , Mediadores de Inflamación/metabolismo , Interferón gamma/biosíntesis , Extractos Vegetales/farmacología , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/metabolismo , Animales , Ratones , Obesidad/inducido químicamente , Obesidad/metabolismo , Extractos Vegetales/química , Glutamato de SodioRESUMEN
Ulomoides dermestoides is a beetle traditionally consumed to treat diabetes. In this study, we performed a composition analysis of U. dermestoides to obtain the principal fractions, which were used to assess the effect on glycemia, liver and pancreatic architecture, and PPARγ and GLUT4 expression. Normal mice and alloxan-induced diabetic mice were administered fractions of chitin, protein or fat, and the acute hypoglycemic effect was evaluated. A subacute study involving daily administration of these fractions to diabetic mice was also performed over 30 days, after which the liver and pancreas were processed by conventional histological techniques and stained with hematoxylin and eosin to evaluate morphological changes. The most active fraction, the fat fraction, was analyzed by gas chromatography-mass spectrometry (GC-MS), and PPARγ and GLUT4 mRNA expressions were determined in 3T3-L1 adipocytes. The protein and fat fractions exhibited hypoglycemic effects in the acute as well as in the 30-day study. Only the fat fraction led to elevated insulin levels and reduced glycemia, as well as lower intake of water and food. In the liver, we observed recovery of close hepatic cords in the central lobule vein following treatment with the fat fraction, while in the pancreas there was an increased density and percentage of islets and number of cells per islet, suggesting cellular regeneration. The GC-MS analysis of fat revealed three fatty acids as the major components. Finally, increased expression of PPARγ and GLUT4 was observed in 3T3-L1 adipocytes, indicating an antidiabetic effect.
Asunto(s)
Escarabajos/química , Cuerpo Adiposo/química , Hipoglucemiantes/uso terapéutico , Hígado/efectos de los fármacos , Páncreas/efectos de los fármacos , Extractos de Tejidos/uso terapéutico , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Cromatografía de Gases y Espectrometría de Masas , Regulación de la Expresión Génica , Transportador de Glucosa de Tipo 4/efectos de los fármacos , Transportador de Glucosa de Tipo 4/metabolismo , Hipoglucemiantes/aislamiento & purificación , Hígado/metabolismo , Hígado/patología , Masculino , PPAR gamma/efectos de los fármacos , PPAR gamma/metabolismo , Páncreas/metabolismo , Páncreas/patología , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Extractos de Tejidos/aislamiento & purificaciónRESUMEN
Ulomoides dermestoides is a beetle traditionally consumed to treat diabetes. In this study, we performed a composition analysis of U. dermestoides to obtain the principal fractions, which were used to assess the effect on glycemia, liver and pancreatic architecture, and PPARγ and GLUT4 expression. Normal mice and alloxan-induced diabetic mice were administered fractions of chitin, protein or fat, and the acute hypoglycemic effect was evaluated. A subacute study involving daily administration of these fractions to diabetic mice was also performed over 30 days, after which the liver and pancreas were processed by conventional histological techniques and stained with hematoxylin and eosin to evaluate morphological changes. The most active fraction, the fat fraction, was analyzed by gas chromatography-mass spectrometry (GC-MS), and PPARγ and GLUT4 mRNA expressions were determined in 3T3-L1 adipocytes. The protein and fat fractions exhibited hypoglycemic effects in the acute as well as in the 30-day study. Only the fat fraction led to elevated insulin levels and reduced glycemia, as well as lower intake of water and food. In the liver, we observed recovery of close hepatic cords in the central lobule vein following treatment with the fat fraction, while in the pancreas there was an increased density and percentage of islets and number of cells per islet, suggesting cellular regeneration. The GC-MS analysis of fat revealed three fatty acids as the major components. Finally, increased expression of PPARγ and GLUT4 was observed in 3T3-L1 adipocytes, indicating an antidiabetic effect.
Asunto(s)
Animales , Masculino , Páncreas/efectos de los fármacos , Extractos de Tejidos/uso terapéutico , Escarabajos/química , Cuerpo Adiposo/química , Hipoglucemiantes/uso terapéutico , Hígado/efectos de los fármacos , Páncreas/metabolismo , Páncreas/patología , Extractos de Tejidos/aislamiento & purificación , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Regulación de la Expresión Génica , PPAR gamma/efectos de los fármacos , PPAR gamma/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Experimental/tratamiento farmacológico , Transportador de Glucosa de Tipo 4/efectos de los fármacos , Transportador de Glucosa de Tipo 4/metabolismo , Hipoglucemiantes/aislamiento & purificación , Hígado/metabolismo , Hígado/patología , Cromatografía de Gases y Espectrometría de MasasRESUMEN
Type 2 diabetes is characterized by oxidative stress and a chronic low-grade inflammatory state, which also play roles in the pathogenesis of this disease and the accompanying vascular complications by increasing the production of free radicals and pro-inflammatory cytokines. Cucurbita ficifolia Bouché (C. ficifolia) is an edible Mexican plant whose hypoglycemic activity has been demonstrated in several experimental and clinical conditions. Recently, D-chiro-inositol has been proposed as the compound responsible for the hypoglycemic effects; however, the antioxidant and anti-inflammatory potential of this plant has not yet been explored. The aim of this research is to study the influence of a hypoglycemic, D-chiro-inositol-containing fraction from the C. ficifolia fruit (AP-Fraction) on biomarkers of oxidative stress, as well as on the inflammatory cytokines in streptozotocin-induced diabetes. The AP-Fraction obtained from the mature fruit of C. ficifolia contained 3.31 mg of D-chiro-inositol/g of AP-Fraction. The AP-Fraction was administrated daily by gavage to normal mice for 15 days as a preventive treatment. Then these animals were given streptozotocin, and the treatments were continued for an additional 33 days. Pioglitazone was used as a hypoglycemic drug for comparison. Administration of the AP-Fraction significantly increased glutathione (GSH) and decreased malondialdehyde (MDA) in the liver without significantly affecting the levels in other tissues. The AP-Fraction reduced TNF-α and increased IL-6 and IFN-γ in serum. Interestingly, the AP-Fraction also increased IL-10, an anti-inflammatory cytokine. These results suggest that C. ficifolia might be used as an alternative medication for the control of diabetes mellitus and that it has antioxidant and anti-inflammatory properties in addition to its hypoglycemic activity.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Cucurbita/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Inositol/uso terapéutico , Fitoterapia , Animales , Antiinflamatorios/farmacología , Antioxidantes/metabolismo , Antioxidantes/farmacología , Glucemia/metabolismo , Citocinas/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2 , Frutas , Glutatión/metabolismo , Hipoglucemiantes/farmacología , Mediadores de Inflamación/sangre , Inositol/farmacología , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos , Estrés Oxidativo/efectos de los fármacos , Pioglitazona , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Tiazolidinedionas/farmacologíaRESUMEN
Obesity is widely recognized as cause of metabolic syndrome and cardiovascular disease. It is provoked by imbalance between the spending and consumption of energy associated with a chronic inflammatory condition due to excessive storage of fat tissue. Obese patients have an impaired inflammatory profile that contributes to the development of vascular complications, with fat tissue being partially responsible for controlling both processes: energy balance (through PPAR) and inflammatory condition (through inflammatory markers). White adipose tissue produces cytokines (IL-6, TNF-α, resistin, adiponectin, etc.) and participates in a broad spectrum of processes. Recently, glycine has been reported to have anti-inflammatory properties which reduce TNF-α and IL-6 levels and increase adiponectin in 3T3-L1 adipocytes and in fat tissue of obese mice. In this study, the possible regulatory role of glycine on some factors involved in storage and energy burning (PPAR-γ, PPAR-α, PPAR-δ and UCP-2) was analyzed in lean and monosodium glutamate-induced obese mice (MSG/Ob mice). Glycine clearly increased fat tissue PPAR-γ expression in lean but not in MSG/Ob mice. The PPAR-γ and PPAR-α liver expression was repressed in both groups of mice, while the expression of PPAR-δ decreased only in lean mice. Interestingly, glycine treatment also suppressed the expression of UCP-2, TNF-α and IL-6 in lean mice, and increased adiponectin and insulin serum levels. In conclusion, glycine regulates the production of inflammatory cytokines through PPAR-γ. These results provide clues on glycine signaling mechanisms as an anti-inflammatory agent that might be useful for treatment of metabolic and vascular complications associated to inflammation in obesity.
Asunto(s)
Antiinflamatorios/uso terapéutico , Citocinas/metabolismo , Metabolismo Energético/efectos de los fármacos , Glicina/uso terapéutico , Canales Iónicos/metabolismo , Proteínas Mitocondriales/metabolismo , Obesidad/prevención & control , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Tejido Adiposo/efectos de los fármacos , Tejido Adiposo/inmunología , Tejido Adiposo/metabolismo , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Glicina/administración & dosificación , Glicina/farmacología , Insulina/sangre , Interleucina-6/metabolismo , Leptina/sangre , Ratones , Obesidad/inmunología , Obesidad/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Glutamato de Sodio , Factor de Necrosis Tumoral alfa/metabolismo , Proteína Desacopladora 2RESUMEN
ETHNOPHARMACOLOGICAL IMPORTANCE: Psacalium peltatum (H.B.K.) Cass. (Asteraceae) is used medicinally to treat diabetes, rheumatic pains, as well as gastrointestinal and kidney ailments. Previous pharmacological and chemical assays have demonstrated that an aqueous fraction from Psacalium peltatum (AP-fraction) contains a carbohydrate-type compound with hypoglycemic activity. Nevertheless, studies have not yet considered the hypoglycemic action of the AP-faction by sub-chronic administration nor on other healing properties, some of which might be associated with DM2 and other inflammatory processes. AIM OF STUDY: To determine whether a hypoglycemic carbohydrate fraction (AP-fraction) from Psacalium peltatum roots has antioxidant and anti-inflammatory effects in streptozotocin-induced diabetes mice. MATERIAL AND METHODS: Healthy mice received either saline, the AP-fraction with a high content of fructans, or pioglitazone (a positive control) daily by gavage. After 15 days of treatment, these animals received a single intraperitoneal administration of streptozotocin and all treatments were continued for additional 33 days. The antioxidant and anti-inflammatory properties of the AP-fraction were evaluated through the quantification of biomarkers of oxidative stress (glutathione (GSH) and malondialdehyde (MDA)) and inflammation (interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and IL-10). RESULTS: The AP-fraction reduced glycemia and the glycated hemoglobin. Furthermore, animals treated with the AP-fraction had increased GSH, while MDA was decreased in the liver and the heart, without changes in the kidneys and the pancreas. The AP-fraction significantly reduced TNF-α serum levels but did not modify IL-6; in addition, this fraction increased IFN-γ and IL-10 levels. The increase in IL-10 levels may indicate an inhibition of the production of pro-inflammatory cytokines such as TNF-α, whereas the increase in IFN-γ might be indicative of a beneficial effect on the immune system. CONCLUSIONS: The AP-fraction hypoglycemic fructans from Psacalium peltatum roots showed antioxidant and anti-inflammatory properties in mice with streptozotocin-induced diabetes. The Psacalium peltatum hypoglycemic fructans may be valuable in preventing insulin resistance, as well as the development and progression of diabetic complications caused by chronic inflammation.