RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.
Asunto(s)
Glucemia , Diabetes Mellitus Experimental , Ayuno , Hipoglucemiantes , Extractos Vegetales , Periodo Posprandial , Animales , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/sangre , Masculino , Irán , Ratas , Medicina Persa , Ratas Wistar , Hiperglucemia/tratamiento farmacológico , Plantas Medicinales/química , Estreptozocina , Juniperus/químicaRESUMEN
BACKGROUND: Pre-diabetes is an important risk factor for the development of type 2 diabetes and is common in Nigeria. Effective intervention can reverse the underlying pathogenesis of insulin resistance in pre-diabetes. This study aimed to determine and compare the impact of moderate exercise and metformin interventions on insulin resistance among participants with pre-diabetes. MATERIALS AND METHODS: Using a randomised placebo-controlled design, 54 Nigerians with pre-diabetes were selected using simple random sampling. They were offered metformin, moderate exercise or placebo treatment and followed up for 12 weeks. Insulin resistance was assessed before and after the interventions and the outcome was compared. RESULTS: Forty-nine participants with pre-diabetes completed the study. Participants in both the exercise and metformin groups had significantly decreased insulin resistance compared to placebo after 12 weeks of intervention. However, there was a decrease in insulin resistance by 77.3% (homeostasis model assessment-insulin resistance [HOMA-IR]) and an increase in insulin sensitivity by 81.2% (quantitative insulin sensitivity check index [QUICKI]) in the exercise group. In comparison, participants in the metformin group had a decrease in insulin resistance by 66.3% (HOMA-IR) and an increase in insulin sensitivity by 76.2% (QUICKI). CONCLUSION: Amongst Nigerians with pre-diabetes, both moderate exercise and metformin have significantly higher efficacy than placebo in improving insulin resistance. However, moderate exercise improved insulin resistance more than the metformin intervention. Participants in this study need to be followed up for a longer period to assess the long-term effects of these interventions.
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Hipoglucemiantes , Resistencia a la Insulina , Metformina , Estado Prediabético , Humanos , Metformina/uso terapéutico , Femenino , Masculino , Estado Prediabético/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Nigeria , Adulto , Persona de Mediana Edad , Ejercicio Físico/fisiología , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Terapia por Ejercicio/métodos , Resultado del Tratamiento , Pueblo de África OccidentalRESUMEN
Purpose: Effective mucosal delivery of drugs continues to pose a significant challenge owing to the formidable barrier presented by the respiratory tract mucus, which efficiently traps and clears foreign particulates. The surface characteristics of micelles dictate their ability to penetrate the respiratory tract mucus. In this study, polymeric micelles loaded with insulin (INS) were modified using mucus-penetrative polymers. Methods: We prepared and compared polyethylene glycol (PEG)-coated micelles with micelles where cell-penetrating peptide (CPP) is conjugated to PEG. Systematic investigations of the physicochemical and aerosolization properties, performance, in vitro release, mucus and cell penetration, lung function, and pharmacokinetics/pharmacodynamics (PK/PD) of polymeric micelles were performed to evaluate their interaction with the respiratory tract. Results: The nano-micelles, with a particle size of <100 nm, exhibited a sustained-release profile. Interestingly, PEG-coated micelles exhibited higher diffusion and deeper penetration across the mucus layer. In addition, CPP-modified micelles showed enhanced in vitro cell penetration. Finally, in the PK/PD studies, the micellar solution demonstrated higher maximum concentration (Cmax) and AUC0-8h values than subcutaneously administered INS solution, along with a sustained blood glucose-lowering effect that lasted for more than 8 h. Conclusion: This study proposes the use of mucus-penetrating micelle formulations as prospective inhalation nano-carriers capable of efficiently transporting peptides to the respiratory tract.
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Péptidos de Penetración Celular , Insulina , Micelas , Polietilenglicoles , Insulina/administración & dosificación , Insulina/farmacocinética , Insulina/química , Polietilenglicoles/química , Polietilenglicoles/farmacocinética , Animales , Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/farmacocinética , Humanos , Tamaño de la Partícula , Administración por Inhalación , Masculino , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Ratas Sprague-Dawley , Moco/química , Moco/metabolismo , Moco/efectos de los fármacos , Sistemas de Liberación de Medicamentos/métodos , Hipoglucemiantes/farmacocinética , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Mucosa Respiratoria/metabolismo , Mucosa Respiratoria/efectos de los fármacos , Glucemia/efectos de los fármacos , Glucemia/análisisRESUMEN
BACKGROUND: Despite the detrimental impact of abnormal glucose metabolism on cardiovascular prognosis after myocardial infarction (MI), diabetes is both underdiagnosed and undertreated. We investigated associations between structured diabetes care routines in cardiac rehabilitation (CR) and detection and treatment of diabetes at one-year post-MI. METHODS: Center-level data was derived from the Perfect-CR survey, which evaluated work routines applied at Swedish CR centers (n = 76). Work routines involving diabetes care included: (1) routine assessment of fasting glucose and/or HbA1c, (2) routine use of oral glucose tolerance test (OGTT), (3) having regular case rounds with diabetologists, and (4) whether glucose-lowering medication was adjusted by CR physicians. Patient-level data was obtained from the national MI registry SWEDEHEART (n = 7601, 76% male, mean age 62.6 years) and included all post-MI patients irrespective of diabetes diagnosis. Using mixed-effects regression we estimated differences between patients exposed versus. not exposed to the four above-mentioned diabetes care routines. Outcomes were newly detected diabetes and the proportion of patients receiving oral glucose-lowering medication at one-year post-MI. RESULTS: Routine assessment of fasting glucose/HbA1c was performed at 63.2% (n = 48) of the centers, while 38.2% (n = 29) reported using OGTT for detecting glucose abnormalities. Glucose-lowering medication adjusted by CR physicians (n = 13, 17.1%) or regular case rounds with diabetologists (n = 7, 9.2%) were less frequently reported. In total, 4.0% of all patients (n = 304) were diagnosed with diabetes during follow-up and 17.9% (n = 1361) were on oral glucose-lowering treatment one-year post-MI. Routine use of OGTT was associated with a higher rate of newly detected diabetes at one-year (risk ratio [95% confidence interval]: 1.62 [1.26, 1.98], p = 0.0007). At one-year a higher proportion of patients were receiving oral glucose-lowering medication at centers using OGTT (1.22 [1.07, 1.37], p = 0.0046) and where such medication was adjusted by CR physicians (1.31 [1.06, 1.56], p = 0.0155). Compared to having none of the structured diabetes care routines, the more routines implemented the higher the rate of newly detected diabetes (from 0 routines: 2.7% to 4 routines: 6.3%; p for trend = 0.0014). CONCLUSIONS: Having structured routines for diabetes care implemented within CR can improve detection and treatment of diabetes post-MI. A cluster-randomized trial is warranted to ascertain causality.
Asunto(s)
Biomarcadores , Glucemia , Rehabilitación Cardiaca , Diabetes Mellitus , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada , Hipoglucemiantes , Infarto del Miocardio , Sistema de Registros , Humanos , Masculino , Femenino , Persona de Mediana Edad , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Suecia/epidemiología , Anciano , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/rehabilitación , Infarto del Miocardio/terapia , Infarto del Miocardio/epidemiología , Infarto del Miocardio/sangre , Resultado del Tratamiento , Hipoglucemiantes/uso terapéutico , Hemoglobina Glucada/metabolismo , Factores de Tiempo , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Diabetes Mellitus/sangre , Diabetes Mellitus/terapia , Biomarcadores/sangre , Valor Predictivo de las Pruebas , Control Glucémico , Encuestas de Atención de la Salud , Pautas de la Práctica en MedicinaRESUMEN
High blood glucose and insufficient angiogenesis in diabetic wounds prevent healing, often leading to amputation or death. To address this, a multifunctional emulsion loaded with simvastatin and stabilized by enzymes was synthesized using ultrasound-assisted emulsification. This emulsion promotes angiogenesis and reduces blood glucose levels. Glucose oxidase and catalase at the emulsion interface catalyze a glucose cascading response, lowering the glucose concentration at the diabetic wound site and improving the wound microenvironment. Simvastatin in the emulsion further promotes angiogenesis. The emulsion significantly accelerated wound healing in diabetic rats, offering a promising approach to diabetic wound management.
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Diabetes Mellitus Experimental , Emulsiones , Glucosa Oxidasa , Cicatrización de Heridas , Animales , Emulsiones/química , Cicatrización de Heridas/efectos de los fármacos , Ratas , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucosa Oxidasa/química , Glucosa Oxidasa/metabolismo , Simvastatina/química , Simvastatina/farmacología , Catalasa/química , Catalasa/metabolismo , Oxígeno/química , Glucemia/efectos de los fármacos , Ratas Sprague-DawleyRESUMEN
6'-Sialyllactose (6'-SL), found in human breast milk, exhibits anti-inflammatory, immune function-enhancing, brain development-promoting, and gut health-improving effects. However, its effects on muscle fatigue remain unknown. Here, we aimed to investigate the effects of 6'-SL on blood lactate level, muscle fiber type, and oxidative phosphorylation protein complexes (OXPHOS) in muscle after exercise using C57BL/6J male mice. C57BL/6J mice were randomly assigned to control or 100 mg/kg 6'-SL. After 12 weeks of 6'-SL administration, the mice were made to perform treadmill exercise; their blood lactate and glucose levels were measured at the basal level (rest) and 0, 5, and 10 min after treadmill exercise. Results showed that 6'-SL treatment in C57BL/6J mice significantly reduced blood lactate level and improved blood glucose level. Moreover, 6'-SL increased the expression of slow-myosin heavy chain (MHC) and OXPHOS in gastrocnemius muscle. In addition, 6'-SL treatment for 12 weeks did not affect food intake, serum biomarkers of tissue injury, and lipid profiles compared with those of the controls. These findings indicate that non-toxic 6'-SL suppressed muscle fatigue during exercise by promoting protein expression of muscle fibers, especially slow-twitch muscle fibers characterized by abundant OXPHOS complexes and decreased blood lactate level. This study suggests that 6'-SL holds promise as a nutritional supplement in exercise and clinical settings, subject to further validation.
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Ácido Láctico , Ratones Endogámicos C57BL , Fatiga Muscular , Músculo Esquelético , Condicionamiento Físico Animal , Animales , Masculino , Ácido Láctico/sangre , Ratones , Fatiga Muscular/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Lactosa/análogos & derivados , Lactosa/farmacología , Glucemia/metabolismo , Glucemia/efectos de los fármacosRESUMEN
There is evidence that nitric oxide (NO) modulates the metabolism of glucose and lipid, and some antihypertensive medications have been shown to affect glucose and lipid metabolism. Peristrophe bivalvis is a medicinal plant that has been shown to have antihypertensive properties. The study investigated the effect of aqueous extract of Peristrophe bivalvis leaf (APB) on fasting blood glucose level (FBG) and lipid profile in rats pretreated with nitro-L-arginine methyl ester (L-NAME). Male Wistar rats (150-170 g, n=30) were randomly divided into two groups: control (CT, n=5) and L-NAME pretreated (n=25). CT received 5 mL/kg of distilled water [DW]) while L-NAME pretreated group received 60 mg/kg of L-NAME (L-NAME60) for eight weeks. After eight weeks, the L-NAME pretreated group was randomly subdivided into L-NAME group (LN), L-NAME recovery group (LRE), L-NAME ramipril group (LRA), and L-NAME APB group (LAPB). The groups received L-NAME60+DW, DW, L-NAME60+10 mg/kg ramipril, and L-NAME60+APB (200 mg/kg), respectively, for five weeks. Serum NO, lipid profile, cyclic guanosine monophosphate (cGMP), and insulin were measured by spectrophotometry, assay kits, and ELISA, respectively. Data were analysed using ANOVA at p < 0.05. At the eighth week, a fall in FBG and an increase in triglyceride, total cholesterol, and low-density lipoprotein cholesterol were recorded in L8 compared to CT. The same effects were also noticed in the thirteenth week in LN. However, FBG was significantly increased and lipid levels were decreased in LAPB compared to LN. A significant increase was observed in cGMP level in LAPB compared to LN. The study showed that APB corrected the hyperlipidemia and hypoglycemia caused by L-NAME, and this effect might be via the activation of cGMP.
Asunto(s)
Glucemia , Lípidos , NG-Nitroarginina Metil Éster , Extractos Vegetales , Hojas de la Planta , Ratas Wistar , Animales , Masculino , Extractos Vegetales/farmacología , Glucemia/metabolismo , Glucemia/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Hojas de la Planta/química , Ratas , Lípidos/sangre , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico/sangre , Inhibidores Enzimáticos/farmacologíaRESUMEN
Gestational diabetes mellitus (GDM) is a common disease during pregnancy that has adverse effects on both the mother and fetus. There are currently rare researches on the effect of vitamin supplementation on GDM pregnant mother and their offspring on animal and cell levels systematically. This work supplemented the GDM pregnant mouse model with vitamin D and found that vitamin D can effectively alleviate the hyperglycemia in GDM pregnant mice, increase blood insulin and adiponectin concentrations, and improve GTT and ITT in pregnant mice. In addition, vitamin D can reduce the incidence of death and high birth weight of offspring caused by GDM. The offspring of GDM pregnant mice had higher blood glucose levels in the first 5 weeks after birth compared to the normal group, and then returned to normal levels. Vitamin D can alleviate abnormal glucose metabolism in newborn mice. The therapeutic effect exhibited by vitamin D may be due to their anti-inflammatory effects, as vitamin D supplementation significantly reduces the levels of TFN-?, MCP-1, IL-1? and IL-8 in the blood. Vitamin D also regulates liver lipid metabolism, resulting in a decrease in liver lipid accumulation and a decrease in blood triglycerides (TG) and cholesterol (CHO). The results of this study demonstrate that vitamin D supplementation can serve as an effective treatment strategy for alleviating GDM symptoms. Keywords: Gestational diabetes mellitus, Vitamin D, Glucose metabolism, Anti-inflammatory.
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Glucemia , Diabetes Gestacional , Modelos Animales de Enfermedad , Vitamina D , Animales , Diabetes Gestacional/metabolismo , Diabetes Gestacional/prevención & control , Diabetes Gestacional/sangre , Diabetes Gestacional/tratamiento farmacológico , Femenino , Embarazo , Vitamina D/farmacología , Vitamina D/uso terapéutico , Ratones , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Glucosa/metabolismo , Suplementos Dietéticos , Ratones Endogámicos C57BLRESUMEN
Background: Semaglutide is a glucagon-like peptide-1 receptor agonists (GLP-1-RAs) approved for the treatment of type 2 diabetes mellitus (T2DM) at doses up to 1 mg. The results from randomized control trials and real-world studies revealed that weekly semaglutide was associated with significant improvements in HbA1c and body weight. To our knowledge, no study assessed the effectiveness of using semaglutide for patients with T2DM in the Saudi population. We aim to assess the effectiveness of once weekly SC 0.5 and 1 mg of semaglutide on HbA1c and weight reduction in patients with T2DM in the Saudi population within 12 months of use, evaluate the predictors of response, and compare the effect of the two doses. Method: This is a retrospective cohort study conducted at Security Force Hospital in Riyadh, Saudi Arabia. Using electronic medical records of patients with type two diabetes who received semaglutide 0.5 or 1 mg for a total duration of at least 12 months of use. Results: Within the study period of semaglutide use, HbA1c significantly decreased from baseline by -2.1% (-2.3 to -1.91, 95% CI) (P <0.001). While the mean change in weight was -6.19 kg (-6.66 to -5.72, 95% CI) (P<0.001). Moreover, BMI, FBG, total cholesterol, LDL, and TG all decreased significantly from baseline (p<0.001). When comparing the sub-groups of 0.5 and 1 mg doses, although results were numerically favorable of 1 mg, there were no statistically significant differences in HbA1c % (-2.1 ± 1.8 vs. -2.1 ± 1.9, p-value= 0.934, respectively), and weight (-6.1 ± 5 vs. -6.2 ± 4.4 kg, p-value=0.837, respectively). Significant predictors of HbA1c reduction were the duration of DM, baseline HbA1c, and insulin therapy. While the significant predictor for weight reduction was insulin therapy. Conclusion: This study is document the effectiveness of once-weekly SC semaglutide on glycemic control and weight loss in real-world practice. We recommend a starting goal dose of 0.5 mg and gradual increase of dose based individual patient response. further studies are needed to assess the effectiveness and tolerability of various semagltude doses.
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Diabetes Mellitus Tipo 2 , Péptidos Similares al Glucagón , Hemoglobina Glucada , Hipoglucemiantes , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/sangre , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/administración & dosificación , Hemoglobina Glucada/análisis , Arabia Saudita/epidemiología , Adulto , Anciano , Resultado del Tratamiento , Glucemia/efectos de los fármacos , Glucemia/análisis , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Pérdida de Peso/efectos de los fármacosRESUMEN
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is common in type 2 diabetes mellitus (T2D), leading to high morbidity and mortality. Managing HFpEF in diabetic patients is challenging with limited treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown potential cardiovascular benefits. This meta-analysis compares the effects of GLP1-RA and SGLT2 inhibitors on HFpEF in T2D patients. METHODS: We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating GLP1-RA and SGLT2 inhibitors' impact on HFpEF in T2D patients. Databases searched included PubMed, MEDLINE, and Cochrane Library up to July 2024. Primary outcomes were changes in left ventricular ejection fraction (LVEF), myocardial fibrosis (extracellular volume fraction, ECV), and functional capacity (6-minute walk test, 6MWT). Secondary outcomes included HbA1c, body weight, and systolic blood pressure (SBP). RESULTS: Twelve studies with 3,428 patients (GLP1-RA: 1,654; SGLT2 inhibitors: 1,774) were included. Both GLP1-RA and SGLT2 inhibitors significantly improved LVEF compared to placebo (GLP1-RA: mean difference [MD] 2.8%, 95% confidence interval [CI] 1.5 to 4.1, p < 0.001; SGLT2 inhibitors: MD 3.2%, 95% CI 2.0 to 4.4, p < 0.001). SGLT2 inhibitors significantly reduced myocardial fibrosis (MD -3.5%, 95% CI -4.2 to -2.8, p < 0.001) more than GLP1-RA (MD -2.3%, 95% CI -3.0 to -1.6, p < 0.001). Functional capacity improved significantly with both treatments (GLP1-RA: MD 45 m, 95% CI 30 to 60, p < 0.001; SGLT2 inhibitors: MD 50 m, 95% CI 35 to 65, p < 0.001). Secondary outcomes showed reductions in HbA1c (GLP1-RA: MD -1.1%, 95% CI -1.4 to -0.8, p < 0.001; SGLT2 inhibitors: MD -1.0%, 95% CI -1.3 to -0.7, p < 0.001) and body weight (GLP1-RA: MD -2.5 kg, 95% CI -3.1 to -1.9, p < 0.001; SGLT2 inhibitors: MD -2.0 kg, 95% CI -2.6 to -1.4, p < 0.001). Both treatments significantly lowered SBP (GLP1-RA: MD -5.2 mmHg, 95% CI -6.5 to -3.9, p < 0.001; SGLT2 inhibitors: MD -4.8 mmHg, 95% CI -6.0 to -3.6, p < 0.001). CONCLUSIONS: GLP1-RA and SGLT2 inhibitors significantly benefit HFpEF management in T2D patients. SGLT2 inhibitors reduce myocardial fibrosis more effectively, while both improve LVEF, functional capacity, and metabolic parameters. These therapies should be integral to HFpEF management in diabetic patients. Further research is needed on long-term outcomes and potential combined therapy effects.
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Diabetes Mellitus Tipo 2 , Receptor del Péptido 1 Similar al Glucagón , Insuficiencia Cardíaca , Incretinas , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Volumen Sistólico , Función Ventricular Izquierda , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Volumen Sistólico/efectos de los fármacos , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Receptor del Péptido 1 Similar al Glucagón/agonistas , Función Ventricular Izquierda/efectos de los fármacos , Resultado del Tratamiento , Incretinas/uso terapéutico , Incretinas/efectos adversos , Masculino , Anciano , Persona de Mediana Edad , Femenino , Recuperación de la Función , Estudios Observacionales como Asunto , Hipoglucemiantes/uso terapéutico , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Tolerancia al Ejercicio/efectos de los fármacos , Factores de Riesgo , Agonistas Receptor de Péptidos Similares al GlucagónRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease is the most common neurodegenerative disease with therapeutic limitations. Insulin resistance plays a role in the progression of Alzheimer's disease. Therapies that modulate insulin secretion and signaling, as well as oxidative stress in the brain are now being investigated for their potential role in the prevention of Alzheimer's disease (AD). Terminalia macroptera (Combretaceae) is a plant that different parts have been used traditionally for the treatment of metabolic and neurological conditions. Previous study has indicated that the crude extract exhibit anti-diabetic property. In addition, the plant is a rich source of tannins, phenolic acids, flavonoids, triterpenes. However, there is no study on its protective effect against biochemical alterations of AD in diabetic rats. AIM OF THE STUDY: The present research study investigated the neuroprotective effects of TeMac™ on Alzheimer-like pathology induced by aluminum chloride (AlCl3) in diabetic rats. METHODS: A phytochemical analysis of TeMac™ was carried out to quantify tannins. The potential effect of the tannins-enriched fraction (TEF) of TeMac™ to prevent the formation of senile plaques was conducted by its ability to inhibit the activities of ß-secretase (EC 3.4.23.46), monoamine oxidase A (EC 1.4.3.4) and the fibrillation of Aß. A diabetic model was induced from female Wistar rats by a single intraperitoneal injection of streptozotocin (STZ, 35 mg/kg BW). After that, the blood glucose level was measured to confirm the induction of diabetes. Three days after induction, animals received AlCl3 (75 mg/kg BW) alone (AD control) or concomitantly with 400 mg/kg BW of TEF of TeMac™ or 5 mg/kg BW Daonil by daily gavage for 42 days. At the end of the experiment, rats were sacrificed, blood and brains were collected. The levels of amyloid fibrils, glucose, albumin and the activities of DPP4, ß-secretase and phosphatase, and markers of oxidative stress in the brain were assessed. RESULTS: TEF of TeMac™ displays a potential ability to inhibit the activities of ß-secretase, monoamine oxidase, and Aß fibrillation. Treatment with TEF of TeMac™ significantly inhibited DPP4 and BACE1 activities and reduced brain glucose and amyloid fibril levels, and improved cerebral albumin levels and modulated oxidative stress markers. CONCLUSION: Our findings indicate that TEF of TeMac™ prevents Alzheimer's-type pathology linked to insulin resistance in rats. TEF of TeMac™ may be a potential drug candidate for the treatment of diabetes-associated cognitive impairment.
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Cloruro de Aluminio , Enfermedad de Alzheimer , Diabetes Mellitus Experimental , Resistencia a la Insulina , Estrés Oxidativo , Extractos Vegetales , Ratas Wistar , Taninos , Animales , Estrés Oxidativo/efectos de los fármacos , Taninos/farmacología , Cloruro de Aluminio/toxicidad , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/prevención & control , Enfermedad de Alzheimer/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/inducido químicamente , Extractos Vegetales/farmacología , Ratas , Fármacos Neuroprotectores/farmacología , Masculino , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Glucemia/efectos de los fármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Zhenzhu Tiaozhi (FTZ) capsule is a hospital preparation of a patented traditional Chinese medicine compound. FTZ has been clinically used for nearly 13 years in the treatment of diabetes and glycolipid metabolic diseases. With the significant benefits of SGLT2 inhibitor in patients with diabetic kidney disease (DKD), it provides a research avenue to explore the mechanism of FTZ in treating this disease based on glycolysis pathway. AIM OF THE STUDY: To explore the pharmacological characteristics of FTZ in DKD mice and its impact on the glycolysis pathway. MATERIALS AND METHODS: We induced a DKD model in C57BL/6 mice by injection of streptozotocin (STZ) combined with long-term high-fat diet. We administered three doses of FTZ for 12 weeks of treatment. Kidney function, blood lipid levels, glucose tolerance, and key glycolytic enzymes were evaluated. Renal pathological changes were observed using HE, MASSON, and PAS staining. The potential targets of the active ingredients of FTZ in the glycolysis pathway were predicted using network pharmacology and molecular docking. Validation was performed using immunohistochemistry and Western blotting. RESULTS: FTZ effectively reduces blood glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, 24 h proteinuria, serum creatinine, blood urea nitrogen, and increases urinary glucose levels. Glucose tolerance and renal pathological changes were significantly improved by FTZ treatment. Pinusolidic acid, a component of FTZ, shows good binding affinity with three active pockets of SGLT2. WB and immunohistochemistry revealed that FTZ significantly inhibits the expression of SGLT2 and its glycolytic related proteins (GLUT2/PKM2/HK2). Hexokinase, pyruvate kinase, and lactate dehydrogenase in the kidney were also significantly inhibited by FTZ in a dose-dependent manner. CONCLUSION: FTZ may alleviate the progression of DKD by inhibiting the activation of the SGLT2/glycolytic pathway. Our study provides new insights into the clinical application of FTZ in DKD.
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Diabetes Mellitus Experimental , Nefropatías Diabéticas , Medicamentos Herbarios Chinos , Glucólisis , Ratones Endogámicos C57BL , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Transportador 2 de Sodio-Glucosa , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Masculino , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Glucólisis/efectos de los fármacos , Transportador 2 de Sodio-Glucosa/metabolismo , Ratones , Glucemia/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Simulación del Acoplamiento Molecular , Estreptozocina , Cápsulas , Dieta Alta en Grasa/efectos adversosRESUMEN
This study aimed to evaluate the effects of supplementation with ethanolic and aqueous extracts from the bark of the stem of Guazuma ulmifolia in mice submitted to a high-fat diet as well as to evaluate the chemical composition of these extracts. The chemical composition and antioxidant potential was evaluated in aqueous and ethanolic extracts of the stem bark. The in vivo test consisted of evaluating the effects of the aqueous and ethanolic extracts of the stem bark on C57BL/6 mice receiving a high-fat diet. The animals were evaluated for weight gain, feed consumption, visceral adiposity, serum, and inflammatory and hormonal parameters. The results of the chemical analyses corroborate those obtained by the literature, which reported gallocatechin, epigallocatechin and epigallocatechin gallate. Compared with the ethanolic extract, the aqueous extract showed greater antioxidant capacity. Both extracts resulted in lower feed consumption in the animals, but they did not influence weight gain or visceral adiposity and resulted in varied changes in the lipid profile. In addition, they did not influence glucose tolerance, insulin sensitivity, or fasting blood glucose. Furthermore, the leptin levels increased, which may have contributed to satiety, but this was shown to have a negative impact on other inflammatory and hormonal parameters. Therefore, under the conditions of this study, the biologically active compounds present in the plant species Guazuma ulmifolia were not able to contribute to the treatment of metabolic changes related to the consumption of a high-fat diet.
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Antioxidantes , Dieta Alta en Grasa , Enfermedades Metabólicas , Ratones Endogámicos C57BL , Corteza de la Planta , Extractos Vegetales , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Dieta Alta en Grasa/efectos adversos , Corteza de la Planta/química , Ratones , Enfermedades Metabólicas/tratamiento farmacológico , Enfermedades Metabólicas/prevención & control , Enfermedades Metabólicas/etiología , Antioxidantes/farmacología , Masculino , Apocynaceae/química , Tallos de la Planta/química , Glucemia/efectos de los fármacosRESUMEN
Rosa davurica Pall. is widely used in traditional oriental herbal therapy, but its components and molecular mechanisms of action remain unclear. This study investigates the antidiabetic potential of Rosa davurica Pall. root extract (RDR) and elucidates its underlying molecular mechanisms with in vitro and in vivo models. Data from the current study show that RDR exhibits strong antioxidant activity and glucose homeostasis regulatory effects. It significantly impacts glucose homeostasis in C2C12 skeletal muscle cells by inhibiting α-glucosidase activity. Further molecular mechanistic studies revealed that RDR promoted glucose uptake by phosphorylation of AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC), but not Phosphatidylinositol 3-kinase (PI 3-kinase)/Akt in C2C12 skeletal muscle cells. These actions increased the expression and translocation of glucose transporter type 4 (GLUT4) to the plasma membrane. In addition, RDR treatment in the STZ-induced diabetic rats remarkably improved the low body weight, polydipsia, polyphagia, hyperglycemia, and islet architecture and increased the insulin/glucose ratio. The liver (ALT and AST) and kidney marker enzyme (BUN and creatinine) levels were restored by RDR treatment as well. Phytochemical analysis identified eight major constituents in RDR, crucial for its antioxidant and antidiabetic activity. Through the molecular docking of representative glucose transporter GLUT4 with these compounds, it was confirmed that the components of RDR had a significantly high binding score in terms of structural binding. These findings from the current study highlight the antidiabetic effects of RDR. Collectively, our data suggest that RDR might be a potential pharmaceutical natural product for diabetic patients.
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Diabetes Mellitus Experimental , Transportador de Glucosa de Tipo 4 , Hipoglucemiantes , Extractos Vegetales , Raíces de Plantas , Rosa , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Hipoglucemiantes/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/química , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Raíces de Plantas/química , Rosa/química , Ratas , Transportador de Glucosa de Tipo 4/metabolismo , Masculino , Ratones , Antioxidantes/farmacología , Antioxidantes/química , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Línea Celular , Glucosa/metabolismo , Simulación del Acoplamiento Molecular , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismoRESUMEN
Despite the existence of various therapeutic approaches, diabetes mellitus and its complications have been an increasing burden of mortality and disability globally. Hence, it is necessary to evaluate the efficacy and safety of medicinal plants to support existing drugs in treating diabetes. Xanthones, the main secondary metabolites found in Gentiana dinarica and Gentiana utriculosa, display various biological activities. In in vitro cultured and particularly in genetically transformed G. dinarica and G. utriculosa roots, there is a higher content of xanthones. The aim of this study was to investigate and compare antidiabetic properties of secondary metabolites (extracts) prepared from these two Gentiana species, cultured in vitro and genetically transformed with those collected from nature. We compare HPLC secondary metabolite profiles and the content of the main extract compounds of G. dinarica and G. utriculosa methanol extracts with their ability to scavenge DPPH free radicals and inhibit intestinal α-glucosidase in vitro. Anti-hyperglycemic activity of selected extracts was tested further in vivo on glucose-loaded Wistar rats. Our findings reveal that the most prominent radical scavenging potential and potential to control the rise in glucose level, detected in xanthone-rich extracts, were in direct correlation with an accumulation of xanthones norswertianin and norswertianin-1-O-primeveroside in G. dinarica and decussatin and decussatin-1-O-primeveroside in G. utriculosa.
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Gentiana , Hipoglucemiantes , Extractos Vegetales , Ratas Wistar , Xantonas , Gentiana/química , Xantonas/farmacología , Xantonas/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Animales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Ratas , Masculino , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/química , Glucemia/efectos de los fármacos , alfa-Glucosidasas/metabolismo , Cromatografía Líquida de Alta Presión , Diabetes Mellitus Experimental/tratamiento farmacológico , Raíces de Plantas/químicaRESUMEN
Physical inactivity and poor dietary choices contribute to the rise in cardiometabolic diseases in the United States. It remains critical to identify strategies that may mitigate the negative impact of these behaviors. Several studies have shown that the consumption of dietary inorganic nitrate may improve vascular health and glucose regulation in animal models and some human studies. However, the improvements in glucose regulation have yet to be corroborated in humans with type 2 diabetes (T2D). Therefore, the purpose of this study was to assess the acute effects of beetroot juice (BRJ) on glycemic and hemodynamic responses in individuals with T2D while controlling for medication. Seven participants with a clinical diagnosis of T2D were recruited into this study and were temporarily removed from blood pressure- and glucose-lowering medications. Hemodynamic measurements (pulsewave velocity) and an oral glucose tolerance test (glycemic response) were measured following consumption of either BRJ or a denitrolized placebo. Saliva and blood samples were collected at baseline and two and four hours post supplementation to measure changes in nitrate and nitrite concentrations. We detected significant improvements in total plasma glucose exposure (p = 0.022) and the SVR change score (p = 0.009) in the BRJ condition. This study demonstrated that BRJ consumption can improve oral glucose tolerance in individuals with T2D while controlling for medication; however, future larger-cohort randomized controlled trials are needed to confirm if BRJ is a viable treatment for glucose control in individuals with T2D.
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Beta vulgaris , Glucemia , Presión Sanguínea , Diabetes Mellitus Tipo 2 , Jugos de Frutas y Vegetales , Nitratos , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/sangre , Proyectos Piloto , Beta vulgaris/química , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Masculino , Presión Sanguínea/efectos de los fármacos , Femenino , Persona de Mediana Edad , Nitritos/sangre , Prueba de Tolerancia a la Glucosa , Anciano , Método Doble Ciego , AdultoRESUMEN
Sprouts are an attractive food product that contains high amounts of nutritional substances and has pro-health features. Sprout consumption has strongly increased despite its potential risk to health due to its microbial load. Both the safety and shelf life of sprouts may be negatively affected by a high microbial load. To reduce the microbial contamination in sprouts before consumption, the initial microbial load on the seeds needs to be controlled. Many herbal sprouts have been recommended for diabetes, and fenugreek is one of these sprouts. Thus, the current experiment aimed at disinfecting fenugreek seeds using microwave (5, 10, and 20 s) and hot water (30, 45, and 60 s) treatments for different durations. The best-disinfected sprouts with the highest nutritional properties were used to evaluate their influence on streptozocin-induced diabetic rats in comparison with fenugreek seed feeding. Microwave treatments showed the highest sprout length, fresh weight, total free amino acids, antioxidants, reducing sugars, and total phenols. Additionally, microwave seed treatments showed the lowest bacteria and mold counts on sprouts produced relative to hot water treatments, and the best seed treatment was a microwave for 20 s, which gave the best values in this respect. Feeding diabetic rats with different fenugreek seeds or sprout rates (0, 5, 7.5, and 10% w/w) improved body weight, restricted the growth of glucose levels, lowered total cholesterol and triglycerides, and improved HDL compared with the positive control group, and fenugreek sprouts at higher rates showed the maximum improvements in blood glucose, total cholesterol, and triglycerides. Treating fenugreek seed with microwave radiation for 20 s to disinfect the seeds before sprouting is recommended for lowering the microbial load with optimum nutritional and antioxidant activity, and feeding diabetic rats with these sprouts at the rate of 7.5 and 10% had promising effects on hyperglycemia and associated disorders.
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Diabetes Mellitus Experimental , Valor Nutritivo , Semillas , Trigonella , Animales , Trigonella/química , Semillas/química , Ratas , Masculino , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Desinfección/métodos , Microondas , Antioxidantes/farmacología , Ratas Wistar , Extractos VegetalesRESUMEN
In this study, we aimed to explore the hypoglycemic effects of a hydrolysate on Takifugu bimaculatus skin (TBSH). The effect of the dipeptidyl peptidase-IV (DPP-IV) inhibitory activities from different TBSH fractions was investigated on basic indexes, gut hormones, blood lipid indexes, viscera, and the gut microbiota and its metabolites in rats with type 2 diabetes mellitus (T2DM). The results showed that the <1 kDa peptide fraction from TBSH (TBP) exhibited a more potent DPP-IV inhibitory effect (IC50 = 0.45 ± 0.01 mg/mL). T2DM rats were induced with streptozocin, followed by the administration of TBP. The 200 mg/kg TBP mitigated weight loss, lowered fasting blood glucose levels, and increased insulin secretion by 20.47%, 25.23%, and 34.55%, respectively, rectified irregular hormonal fluctuations, lipid metabolism, and tissue injuries, and effectively remedied gut microbiota imbalance. In conclusion, TBP exerts a hypoglycemic effect in rats with T2DM. This study offers the potential to develop nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus. It will provide information for developing nutritional supplements to treat T2DM and further promote the high-value utilization of processing byproducts from T. bimaculatus.
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Glucemia , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Hiperglucemia , Hipoglucemiantes , Péptidos , Piel , Takifugu , Animales , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ratas , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Hipoglucemiantes/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Piel/efectos de los fármacos , Piel/metabolismo , Hiperglucemia/tratamiento farmacológico , Glucemia/efectos de los fármacos , Péptidos/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Metaboloma/efectos de los fármacos , Ratas Sprague-Dawley , Insulina/metabolismo , Insulina/sangreRESUMEN
As a step toward the development of novel small-molecule positive allosteric modulators (PAMs) of glucagon-like peptide 1 receptor (GLP-1R) for the treatment of type 2 diabetes, obesity, and heart diseases, we discovered a novel 2-amino-thiophene (2-AT) based lead compound bearing an ethyl 3-carboxylate appendage. In this work, we report the syntheses and biological studies of more than forty 2-AT analogs, that have revealed a 2-aminothiophene-3-arylketone analogue 7 (MW 299) showing approximately a 2-fold increase in insulin secretion at 5 µM when combined with the GLP-1 peptide at 10 nM. In vivo studies using CD1 mice at a dose of 10 mg/kg, clearly demonstrated that the blood plasma glucose level was lowered by 50% after 60 min. Co-treatment of 7 with sitagliptin, an inhibitor of GLP-1 degrading enzyme Dipeptidyl Peptidase IV, further confirmed 7 to be an effective PAM of GLP-1R. The small molecular weight and demonstrated allosteric modulating properties of these compound series, show the potential of these scaffolds for future drug development.
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Receptor del Péptido 1 Similar al Glucagón , Tiofenos , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Animales , Tiofenos/farmacología , Tiofenos/química , Tiofenos/síntesis química , Regulación Alostérica/efectos de los fármacos , Ratones , Humanos , Relación Estructura-Actividad , Estructura Molecular , Hipoglucemiantes/farmacología , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Relación Dosis-Respuesta a Droga , Insulina/metabolismo , Fosfato de Sitagliptina/farmacología , Fosfato de Sitagliptina/síntesis química , Fosfato de Sitagliptina/químicaRESUMEN
AIMS: To evaluate whether treatment with insulin is advantageous compared with oral anti-diabetic drugs (OAD) for patients newly diagnosed with type 2 diabetes with moderate hyperglycemia. METHODS: Patients newly diagnosed with type 2 diabetes with moderate hyperglycemia were recruited and randomized to receive insulin, metformin or sitagliptin treatment. The oral glucose tolerance test (OGTT) was performed before treatment and 6 months thereafter. The primary outcome was the glycohemoglobin (HbA1c) level change. For the secondary efficacy analysis, the ß-cell function and insulin sensitivity were calculated from the OGTT, as was the proportion of subjects who reached the treatment target (HbA1c level < 7.0 % or < 6.5 %) at 6 months. RESULTS: We randomized 50 patients to the three groups and 32 patients who received the allocated treatment were analyzed. The change of HbA1c level in the insulin, metformin, and sitagliptin groups was - 2.06 ± 1.37 %, -0.43 ± 0.32 %, and - 1.62 ± 0.92 %, respectively. This change was smallest in the metformin group. There was no significant difference in the changes or final HbA1c levels between the insulin and sitagliptin groups. The treat-to-target (HbA1c level < 7.0 %) rates in the insulin, metformin and sitagliptin were 75 %, 50 % and 100 %, respectively. The treat-to-target rates were not significantly different among the three groups. The insulin secretion indices, including the Matsuda index and HOMA-IR, indicated that the groups did not differ after 6 months of therapy. CONCLUSION: A 6-month course of basal insulin therapy did not benefit patients newly diagnosed with diabetes with moderate hyperglycemia in terms of insulin sensitivity or insulin secretion.