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1.
Eur J Pharmacol ; 959: 176068, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37775016

RESUMO

Oxidative stress and inflammation induced by abundant consumption of high-energy foods and caloric overload are implicated in the dysfunction of the blood‒brain barrier (BBB), cognitive impairment, and overactivation of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). These enzymes hydrolyse acetylcholine, affecting anti-inflammatory cholinergic signalling. Our aim was to evaluate whether nicotinamide (NAM) attenuates the impairment of the BBB and cognitive function, improving cholinergic signalling. Forty male rats were distributed into five groups: one group was fed a standard diet, and the remaining groups were fed a high-fat diet and a beverage with 40% sucrose (HFS; high-fat sucrose). In three of the HFS groups, the carbohydrate was replaced by drinking water containing different concentrations of NAM for 5 h every morning for 12 weeks. The biochemical profile, levels of stress and inflammation markers, cholinesterase activities, BBB permeability, and cognitive capacity were evaluated. The results showed that the HFS diet disturbed the metabolism of carbohydrates and lipids, causing insulin resistance. Simultaneously, AChE and BChE activities, levels of proinflammatory cytokines, oxidation of proteins and lipoperoxidation increased along with decreased antioxidant capacity in serum. In the hippocampus, increased activity of cholinesterases, protein carbonylation and lipoperoxidation were associated with decreased antioxidant capacity. Systemic and hippocampal changes were reflected in increased BBB permeability and cognitive impairment. In contrast, NAM attenuated the above changes by reducing oxidative stress and inflammation through decreasing cholinesterase activities, especially by uncompetitive inhibition. NAM may be a potential systemic and neuroprotective agent to mitigate cognitive damage due to hypercaloric diets.


Assuntos
Acetilcolinesterase , Niacinamida , Ratos , Masculino , Animais , Acetilcolinesterase/metabolismo , Niacinamida/farmacologia , Inibidores da Colinesterase/farmacologia , Antioxidantes/metabolismo , Butirilcolinesterase/metabolismo , Barreira Hematoencefálica/metabolismo , Estresse Oxidativo/fisiologia , Cognição , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Dieta Hiperlipídica , Sacarose
2.
Life Sci ; 250: 117585, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32243928

RESUMO

AIMS: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been associated with risk factors for metabolic syndrome (MetS). Our objective was to evaluate the effect of nicotinamide (NAM) on the activities, expression and protein content of cholinesterases in a MetS model. MAIN METHODS: MetS was induced in male rats administrating 40% fructose to the drinking water for 16 weeks. Additionally, from 5th week onward, the carbohydrate solution was replaced by NAM, at several concentrations for 5 h each morning for the next 12 weeks. In the 15th week, the glucose tolerance test was conducted, and blood pressure was measured. After the treatment period had concluded, the biochemical profile; oxidant stress; proinflammatory markers; and the activity, quantity and expression of cholinesterases were evaluated, and molecular docking analysis was performed. KEY FINDINGS: The MetS group showed anthropometric, hemodynamic and biochemical alterations and increased cholinesterase activity, inflammation and stress markers. In the liver, cholinesterase activity and mRNA, free fatty acid, tumor necrosis factor-alpha (TNF-α), and thiobarbituric acid-reactive substance (TBARS) levels were increased, while reduced glutathione (GSH) levels were decreased. NAM partially or totally decreased risk factors for MetS, markers of stress and inflammation, and the activity (serum and liver) and expression (liver) of cholinesterases. Molecular docking analysis showed that NAM has a greater affinity for cholinesterases than acetylcholine (ACh), suggesting NAM as an inhibitor of cholinesterases. SIGNIFICANCE: Supplementation with 40% fructose induced MetS, which increased the activity and expression of cholinesterases, oxidative stress and the inflammation. NAM attenuated these MetS-induced alterations and changes in cholinesterases.


Assuntos
Inflamação/metabolismo , Síndrome Metabólica/tratamento farmacológico , Niacinamida/uso terapêutico , Estresse Oxidativo , Receptores Colinérgicos/metabolismo , Acetilcolinesterase/metabolismo , Animais , Antropometria , Anti-Inflamatórios/uso terapêutico , Arildialquilfosfatase/metabolismo , Butirilcolinesterase/metabolismo , Colinesterases/metabolismo , Frutose , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Hemodinâmica , Humanos , Peroxidação de Lipídeos , Fígado/enzimologia , Masculino , Síndrome Metabólica/induzido quimicamente , Simulação de Acoplamento Molecular , Ratos , Ratos Sprague-Dawley
3.
J Ethnopharmacol ; 144(1): 101-8, 2012 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-22960550

RESUMO

ETHNOPHARMACOLOGICAL IMPORTANCE: Cucurbita ficifolia is used in Mexican traditional medicine as an anti-diabetic and anti-inflammatory agent and its actions can be mediated by antioxidant mechanisms. Disturbance in the homeostasis of glutathione has been implicated in the etiology and progression of diabetes mellitus and its complications. MATERIAL AND METHODS: It was evaluated, the effect of an aqueous extract of Cucurbita ficifolia on glycemia, plasma lipid peroxidation; as well as levels of reduced (GSH) and oxidized (GSSG) glutathione and activities of enzymes involved in glutathione redox cycle: glutathione peroxidase (GPx) and glutathione reductase (GR) in liver, pancreas, kidney and heart homogenates of streptozotocin-induced diabetic mice. RESULTS: Increased blood glucose and lipid peroxidation, together with decreased of GSH concentration, GSH/GSSG ratio and its redox potential (E(h)), and enhanced activity of GPx and GR in liver, pancreas and kidney were the salient features observed in diabetic mice. Administration of the aqueous extract of Cucurbita ficifolia to diabetic mice for 30 days, used at a dose of 200 mg/kg, resulted in a significant reduction in glycemia, polydipsia, hyperphagia and plasma lipid peroxidation. Moreover, GSH was increased in liver, pancreas and kidney, and GSSG was reduced in liver, pancreas and heart, therefore GSH/GSSG ratio and its E(h) were restored. Also, the activities involved in the glutathione cycle were decreased, reaching similar values to controls. CONCLUSIONS: An aqueous extract of Cucurbita ficifolia with hypoglycemic action, improve GSH redox state, increasing glutathione pool, GSH, GSH/GSSG ratio and its E(h), mechanism that can explain, at least in part, its antioxidant properties, supporting its use as an alternative treatment for the control of diabetes mellitus, and prevent the induction of complications by oxidative stress.


Assuntos
Cucurbita , Diabetes Mellitus Experimental/metabolismo , Glutationa/metabolismo , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Frutas , Dissulfeto de Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Medicina Tradicional , Camundongos , Miocárdio/metabolismo , Oxirredução , Pancrelipase/efeitos dos fármacos , Pancrelipase/metabolismo
4.
Am J Chin Med ; 40(1): 97-110, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22298451

RESUMO

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.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Cucurbita/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Inositol/uso terapêutico , Fitoterapia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Glicemia/metabolismo , Citocinas/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2 , Frutas , Glutationa/metabolismo , Hipoglicemiantes/farmacologia , Mediadores da Inflamação/sangue , Inositol/farmacologia , Fígado/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos , Estresse Oxidativo/efeitos dos fármacos , Pioglitazona , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Tiazolidinedionas/farmacologia
5.
J Ethnopharmacol ; 132(2): 400-7, 2010 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-20713141

RESUMO

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.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Asteraceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Frutanos/farmacologia , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios não Esteroides/análise , Glicemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Interferon gama/metabolismo , Interleucina-10/análise , Interleucina-10/metabolismo , Interleucina-6/análise , Interleucina-6/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/química , Raízes de Plantas/química , Fator de Necrose Tumoral alfa/metabolismo
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