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1.
Braz. J. Pharm. Sci. (Online) ; 58: e18628, 2022. tab, graf
Article in English | LILACS | ID: biblio-1364417

ABSTRACT

Abstract Degenerative diseases diabetes and oxidative stress constitute a major health concern worldwide. Medicinal plants are expected to provide effective and affordable remedies. The present research explored antidiabetic and antioxidant potential of extracts of Carissa opaca roots. Methanolic extract (ME) was prepared through maceration. Its fractions were obtained, sequentially, in hexane, chloroform, ethyl acetate and n-butanol. An aqueous decoction (AD) of the finely ground roots was obtained by boiling in distilled water. The leftover biomass with methanol was boiled in water to obtain biomass aqueous decoction (BAD). The extracts and fractions showed considerable porcine pancreatic α-amylase inhibitory activity with IC50 in the range of 5.38-7.12 mg/mL while acarbose had 0.31 mg/mL. The iron chelating activity in terms of EC50 was 0.2939, 0.3429, 0.1876, and 0.1099 mg/mL for AD, BAD, ME, and EDTA, respectively. The EC50 of beta-carotene bleaching activity for AD, BAD, ME, and standard BHA were 4.10, 4.71, 3.48, and 2.79 mg/mL, respectively. The total phenolic content (TPC) and total flavonoid content (TFC) of AD and BAD were also considerable. In general, ethyl acetate fraction proved to be the most potent. Thus, the C. opaca roots had excellent antioxidant activity while having moderate α-amylase inhibitory potentia


Subject(s)
Plants, Medicinal/adverse effects , Plant Extracts/analysis , Iron Chelating Agents/analysis , beta Carotene/analysis , Apocynaceae/classification , Disease , Inhibitory Concentration 50 , Hypoglycemic Agents/pharmacology , Antioxidants
2.
Braz. j. biol ; 81(3): 621-631, July-Sept. 2021. tab, graf
Article in English | LILACS | ID: biblio-1153391

ABSTRACT

Abstract Campomanesia xanthocarpa, a plant belonging to the Myrtaceae family, is popularly known as gabiroba. Leaves of gabiroba has been popularly used to treat various diseases, including inflammatory, renal, and digestive, among others. Additionally, studies have shown an effect to reduce blood cholesterol levels. The aim of this study was to evaluate the antihyperglycemic and hypolipidemic effects of Campomanesia xanthocarpa seed extract in hyperglycemic rats. The results showed that 400 mg/kg of seed extract was able to decrease blood glucose levels and to increase the muscular and hepatic glycogen content as well as to inhibit the sucrase and maltase activity. At doses of 200 mg/kg and 800 mg/kg, the activity of these enzymes was also reduced. In the lipid profile 400 mg/kg produced a decrease in total and LDL cholesterol serum levels; and with 200 mg/kg there was an increase in HDL cholesterol levels. The extract did not present hepatic and renal toxic effects at the different doses tested. The results suggest that the treatment with Campomanesia xanthocarpa seeds extract is useful in reducing glycemia, total cholesterol and LDL levels with potential adjuvant therapeutic in the treatment of diabetes and hypercholesterolemia, however, additional pharmacological and toxicological studies are still required.


Resumo Campomanesia xanthocarpa, planta pertencente à família Mirtaceae, é popularmente conhecida como gabiroba. Folhas da gabiroba são popularmente usadas para tratar de doenças inflamatórias, renais, digestivas entre outras. Além disso, estudos têm mostrado um efeito redutor dos níveis de colesterol. O objetivo deste estudo foi avaliar os efeitos anti-hiperglicêmico e hipolipidêmico do extrato de sementes de Campomanesia xanthocarpa em ratos hiperglicêmicos. Os resultados mostraram que 400 mg/kg do extrato da semente foi capaz de reduzir os níveis de glicose sanguínea e aumentar o conteúdo de glicogênio hepático e muscular, bem como inibir a atividade da maltase e sacarase. Na dose de 200 mg/kg e 800 mg/kg, a atividade das enzimas também foi reduzida. No perfil lipídico, 400 mg/kg produziu uma redução nos níveis séricos de colesterol total e LDL e com 200 mg/kg houve um aumento nos níveis de colesterol HDL. O extrato não apresentou efeitos tóxicos hepáticos e renais nas doses testadas. Os resultados sugerem que o tratamento com o extrato de Campomanesia xanthocarpa é eficaz na redução da glicemia, de colesterol total e LDL com potencial para tratamento adjuvante do diabetes e hipercolesterolemia, no entanto estudos farmacológicos e toxicológicos adicionais são necessários.


Subject(s)
Animals , Rats , Carbon Dioxide , Myrtaceae , Seeds , Plant Extracts/pharmacology , Hypoglycemic Agents/pharmacology
3.
Rev. urug. cardiol ; 36(2): e401, ago. 2021. ilus, tab
Article in Spanish | LILACS, BNUY, UY-BNMED | ID: biblio-1289997

ABSTRACT

La diabetes mellitus, la insuficiencia cardíaca y la enfermedad renal crónica tienen alta prevalencia en la población. Asimismo, estas patologías están comprendidas en un "círculo vicioso" porque comparten mecanismos fisiopatológicos que predisponen a su coexistencia en un mismo paciente, incrementando significativamente el riesgo de eventos cardiovasculares. Recientemente se han agregado al arsenal terapéutico las gliflozinas, un grupo de fármacos con beneficios en las tres enfermedades mencionadas. Saber cómo se desarrolló la investigación con estos fármacos y sus mecanismos de acción es fundamental para optimizar el tratamiento de los pacientes.


Diabetes mellitus, heart failure, and chronic kidney disease are highly prevalent in the population. Likewise, these pathologies are included in a "vicious circle" because they share pathophysiological mechanisms that predispose to their coexistence in the same patient, significantly increasing the risk of cardiovascular events. Gliflozins, a group of drugs with benefits in the three mentioned pathologies, have recently been added to the therapeutic arsenal. Knowing how research with these drugs and its mechanisms of action is essential to optimize the treatment of patients.


Diabetes mellitus, insuficiência cardíaca e doença renal crônica são altamente prevalentes na população. Estas patologias fazem parte de um "círculo vicioso", compartilhando mecanismos fisiopatológicos que predispõem à coexistência no mesmo paciente, e aumentando significativamente o risco de eventos cardiovasculares. As gliflozinas, são un grupo de drogas com benefícios das três patologias citadas, foram adicionadas recentemente ao arsenal terapêutico. Saber como foram desenvolvidas as pesquisas com esses medicamentos e seus mecanismos de ação é essencial para otimizar o tratamento dos pacientes.


Subject(s)
Humans , Diabetes Mellitus/drug therapy , Renal Insufficiency, Chronic/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Heart Failure/drug therapy , Hypoglycemic Agents/pharmacology , Treatment Outcome
4.
Article in Chinese | WPRIM | ID: wpr-878878

ABSTRACT

Polysaccharides are macromolecular compounds formed by more than 10 monosaccharide molecules linked by glycosidic bonds. Polysaccharides have a wide range of sources, high safety and low toxicity, with a variety of biological activities, such as anti-tumor, anti-virus, immune regulation, lowering blood glucose, and lowering blood lipids. Type 2 diabetes mellitus(T2 DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance and low inflammation. In recent years, the treatment of T2 DM with polysaccharide has become a research hotspot. Polysaccharides can not only make up for the side effects such as hypoglycemia, weight gain, gastrointestinal injury caused by long-term treatment of acarbose, biguanidine and sulfonylurea, but also play an effective role in reducing glucose by regulating glucose metabolism, oxidative stress, inflammatory response, intestinal flora, etc. In this paper, the research progress of polysaccharides in the treatment of T2 DM was reviewed. In addition, the hot spots such as the hypoglycemic activity of polysaccharides with structural modifications were summarized, providing theoretical guidance for the development of active polysaccharide hypoglycemic medicines and the further study of action mechanism.


Subject(s)
Blood Glucose , Diabetes Mellitus, Type 2/drug therapy , Humans , Hypoglycemic Agents/pharmacology , Insulin Resistance , Polysaccharides
5.
Bol. latinoam. Caribe plantas med. aromát ; 19(2): 188-206, mar. 2020. ilus, tab
Article in English | LILACS | ID: biblio-1104201

ABSTRACT

The present study aimed to screen the Rhazya stricta Decne root for its antihyperglycemic and antioxidants potential through invitro assays along with phytochemical and elemental analyses. The crude extract was prepared through maceration and fractionated using solvent-solvent extraction technique. The spectroscopic studies indicated the presence of various phytochemical classes in the extract and its fractions. The antioxidant assays showed notable results along with a good concentration of phenolic and flavonoid contents. Enzyme inhibition assays demonstrated glucose-lowering effects by inhibiting the enzyme activity which could reduce post-prandial blood glucose level. The Dipeptidyl peptidase-IV (DPP-IV) inhibition assay results showed the novel DPP-IV inhibition activity of the plant extract and all fractions showed noteworthy enzyme inhibition and antihyperglycemic activity. Conclusively, the Rhazya stricta root extract displayed its antioxidant and antihyperglycemic potential due to the presence of various classes of phytochemicals and micro-nutrients.


El presente estudio tuvo como objetivo examinar la raíz de Rhazya stricta Decne por su potencial antihiperglicémico y antioxidante a través de ensayos in vitro junto con análisis fitoquímicos y elementales. El extracto crudo se preparó por maceración y se fraccionó usando una técnica de extracción solvente-solvente. Los estudios espectroscópicos indicaron la presencia de varias clases fitoquímicas en el extracto y sus fracciones. Los ensayos antioxidantes mostraron resultados notables junto con una importante concentración de contenido fenólico y flavonoide. Los ensayos de inhibición enzimática demostraron efectos reductores de la glucosa al inhibir la actividad enzimática que podría reducir el nivel de glucosa posprandial en sangre. Los resultados del ensayo de inhibición de Dipeptidyl peptidase-IV (DPP-IV) mostraron la nueva actividad de inhibición de DPP-IV del extracto de la planta y todas las fracciones mostraron una notable inhibición enzimática y actividad antihiperglicémica. En conclusión, el extracto de raíz de Rhazya stricta Decne mostró su potencial antioxidante y antihiperglicémico debido a la presencia de varias clases de fitoquímicos y micronutrientes.


Subject(s)
Plant Extracts/pharmacology , Apocynaceae/chemistry , Hypoglycemic Agents/pharmacology , Antioxidants/pharmacology , Phenols/analysis , Spectrophotometry, Ultraviolet , Flavonoids/analysis , Blood Glucose/drug effects , In Vitro Techniques , Plant Extracts/chemistry , Spectroscopy, Fourier Transform Infrared , Plant Roots/chemistry , Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/antagonists & inhibitors , Phytochemicals , Hypoglycemic Agents/chemistry , Antioxidants/chemistry
6.
Electron. j. biotechnol ; 43: 41-47, Jan. 2020. graf, ilus
Article in English | LILACS | ID: biblio-1087517

ABSTRACT

Background: The harmful effects of type 2 diabetes mellitus and its complications have become a major global public health problem. In this study, the effects of Momordica charantia saponins (MCS) on lipid metabolism, oxidative stress, and insulin signaling pathway in type 2 diabetic rats were investigated. Results: MCS could attenuate the tendency of weight loss of the model rats. It could also improve glucose tolerance; reduce fasting blood glucose, nonesterified fatty acid, triglyceride, and total cholesterol; and increase the insulin content and insulin sensitivity index of the rats. The activity of superoxide dismutase and catalase increased, and the content of malondialdehyde decreased in the liver and pancreas tissues of rats in MCS-treated groups significantly. In addition, the expression of p-IRS-1 (Y612) and p-Akt (S473) increased, and the expression of p-IRS-1 (S307) decreased in the liver tissues and pancreas tissues of rats in MCS-treated groups significantly. Conclusion: MCS has an antidiabetic effect, which may be related to its improving the lipid metabolism disorder, reducing oxidative stress level, and regulating the insulin signaling pathway.


Subject(s)
Animals , Male , Rats , Saponins/therapeutic use , Momordica charantia/chemistry , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/therapeutic use , Pancreas/drug effects , Saponins/pharmacology , Blood Glucose/drug effects , Body Weight , Insulin Resistance , Rats, Wistar , Oxidative Stress/drug effects , Hypoglycemic Agents/pharmacology , Lipids , Liver/drug effects
7.
Rev. Assoc. Med. Bras. (1992) ; 66(supl.1): s17-s24, 2020. tab, graf
Article in English | LILACS | ID: biblio-1057108

ABSTRACT

SUMMARY Type 2 diabetes mellitus is an important public health problem, with a significant impact on cardiovascular morbidity and mortality and an important risk factor for chronic kidney disease. Various hypoglycemic therapies have proved to be beneficial to clinical outcomes, while others have failed to provide an improvement in cardiovascular and renal failure, only reducing blood glucose levels. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, represented by the empagliflozin, dapagliflozin, and canagliflozin, have been showing satisfactory and strong results in several clinical trials, especially regarding the reduction of cardiovascular mortality, reduction of hospitalization due to heart failure, reduction of albuminuria, and long-term maintenance of the glomerular filtration rate. The benefit from SGLT2 inhibitors stems from its main mechanism of action, which occurs in the proximal tubule of the nephron, causing glycosuria, and a consequent increase in natriuresis. This leads to increased sodium intake by the juxtaglomerular apparatus, activating the tubule glomerular-feedback and, finally, reducing intraglomerular hypertension, a frequent physiopathological condition in kidney disease caused by diabetes. In addition, this class of medication presents an appropriate safety profile, and its most frequently reported complication is an increase in the incidence of genital infections. Thus, these hypoglycemic agents gained space in practical recommendations for the management of type 2 diabetes mellitus and should be part of the initial therapeutic approach to provide, in addition to glycemic control, cardiovascular outcomes, and the renoprotection in the long term.


Subject(s)
Humans , Cardiovascular Diseases/prevention & control , Diabetes Mellitus, Type 2/drug therapy , Sodium-Glucose Transporter 2/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Hypoglycemic Agents/pharmacology , Kidney Diseases/prevention & control , Benzhydryl Compounds/therapeutic use , Cardiovascular Diseases/etiology , Cardiovascular Diseases/mortality , Diabetes Mellitus, Type 2/complications , Diabetic Nephropathies/etiology , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/prevention & control , Sodium-Glucose Transporter 2/therapeutic use , Canagliflozin/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Glomerular Filtration Rate , Glucose/metabolism , Glucosides/therapeutic use , Hypoglycemic Agents/therapeutic use , Kidney/drug effects , Kidney/physiopathology , Kidney/metabolism , Kidney Diseases/etiology , Kidney Diseases/metabolism
8.
Article in Chinese | WPRIM | ID: wpr-879924

ABSTRACT

Endothelial progenitor cells (EPCs) play an important role in diabetic vascular complications. A large number of studies have revealed that some clinical antihyperglycemics can improve the complications of diabetes by regulating the function of EPCs. Metformin can improve EPCs function in diabetic patients by regulating oxidative stress level or downstream signaling pathway of adenosine monophosphate activated protein kinase; Pioglitazone can delay the aging of EPCs by regulating telomerase activity; acarbose, sitagliptin and insulin can promote the proliferation, migration and adhesion of EPCs. In addition to lowering blood glucose, the effects of antihyperglycemics on EPCs may also be one of the mechanisms to improve the complications of diabetes. This article reviews the research progress on the regulation of EPC proliferation and function by antihyperglycemics.


Subject(s)
Cell Movement/drug effects , Cells, Cultured , Endothelial Progenitor Cells/drug effects , Humans , Hypoglycemic Agents/pharmacology , Signal Transduction/drug effects
9.
Rev. Assoc. Med. Bras. (1992) ; 65(9): 1144-1150, Sept. 2019. tab, graf
Article in English | LILACS | ID: biblio-1041074

ABSTRACT

SUMMARY OBJECTIVE In view of the high incidence of polycystic ovary syndrome (PCOS) and the unsatisfactory therapeutic effects of dimethyldiguanide or clomifene citrate alone, our study aimed to investigate the therapeutic effects of dimethyldiguanide combined with clomifene citrate in the treatment of PCOS. METHODS A total of 79 patients with POCS and 35 healthy females were included, and endometrial biopsies were obtained. The sterol regulatory element-binding protein-1 (SREBP1) expression in endometrial tissues was detected by qRT-PCR. POC patients were randomly divided into group A (n=40) and group B (n=39). Patients in group A were treated with dimethyldiguanide combined with clomifene citrate, while patients in group B were treated with clomifene citrate alone. The number of mature follicles and cervical mucus score, follicular development rate and single follicle ovulation rate, cycle pregnancy rate, early miscarriage rate, ovulation rate, endometrial thickness, positive rate of three lines sign, follicle stimulating hormone level and luteinizing hormone level were compared between the two groups. RESULTS The expression level of SREBP1 was higher in PCOS patients than that in the healthy control. SREBP1 expression was inhibited after treatment, while the inhibitory effects of combined treatment were stronger than those of clomifene citrate alone. Compared with clomifene citrate alone, the combined treatment improved cervical mucus score, follicle development rate, single follicle ovulation rate, endometrial thickness, positive rate of three lines sign, and follicle-stimulating hormone level. CONCLUSION The therapeutic effect of combined treatment is better than clomifene citrate alone in the treatment of PCOS.


RESUMO OBJETIVO Tendo em vista a alta incidência de síndrome dos ovários policísticos (SOP) e os efeitos terapêuticos insatisfatórios da dimetildiguanida ou do citrato de clomifeno isoladamente, nosso estudo teve como objetivo investigar os efeitos terapêuticos da dimetildiguanida associada ao citrato de clomifeno no tratamento da SOP. MÉTODOS Um total de 79 pacientes com POCS e 35 mulheres saudáveis foram incluídos, e biópsias endometriais foram obtidas. A expressão da proteína de ligação do elemento regulador de esterol-1 (SREBP1) nos tecidos endometriais foi detectada por qRT-PCR. Pacientes POC foram divididos aleatoriamente em grupo A (n=40) e grupo B (n=39). Os pacientes do grupo A foram tratados com dimetildiguanida combinada com citrato de clomifeno, enquanto os pacientes do grupo B foram tratados apenas com citrato de clomifeno. O número de folículos maduros e muco cervical, taxa de desenvolvimento folicular e taxa de ovulação, taxa de gravidez, abortamento precoce, taxa de ovulação, espessura endometrial, taxa positiva de três linhas, nível de hormônio folículo estimulante e nível de hormônio luteinizante foram comparados entre os dois grupos. RESULTADOS O nível de expressão do SREBP1 foi maior nos pacientes com SOP do que no controle normal. A expressão de SREBP1 foi inibida após o tratamento, enquanto os efeitos inibidores do tratamento combinado foram mais fortes do que os do citrato de clomifeno isoladamente. Comparado com o citrato de clomifeno sozinho, o tratamento combinado melhorou significativamente a pontuação do muco cervical, a taxa de desenvolvimento folicular, a taxa de ovulação do folículo único, a espessura endometrial, a taxa positiva de três linhas de sinal e o nível de hormônio folículo estimulante. CONCLUSÃO O efeito terapêutico do tratamento combinado é melhor do que o citrato de clomifeno isolado no tratamento da SOP.


Subject(s)
Humans , Female , Adult , Young Adult , Polycystic Ovary Syndrome/drug therapy , Clomiphene/therapeutic use , Fertility Agents, Female/therapeutic use , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Ovulation Induction , Cervix Mucus/drug effects , Gene Expression Regulation/drug effects , Clomiphene/pharmacology , Drug Therapy, Combination , Endometrium/physiopathology , Sterol Regulatory Element Binding Protein 1/adverse effects , Sterol Regulatory Element Binding Protein 1/genetics , Fertility Agents, Female/pharmacology , Ovarian Follicle/drug effects , Hypoglycemic Agents/pharmacology , Metformin/pharmacology
10.
Braz. j. pharm. sci ; 55: e18157, 2019. tab, graf
Article in English | LILACS | ID: biblio-1011648

ABSTRACT

In the current study, four Onobrychis species, O. albiflora Hub.-Mor., O. argyrea Boiss. subsp. argyrea Boiss., O. galegifolia Boiss., and O. tournefortii (Willd.) Desv. were collected from Anatolia to be evaluated for their antidiabetic activities. Methanol water extracts of the aerial parts were used for experiments. An alloxan-induced diabetic mice test model was used. Phytochemical analysis of the tested extracts was investigated using the HPLC method. The highest activity was observed with treatment of O. albiflora aerial part extract. Significant decrements were detected in the blood glucose levels as follows: 180.83±47.48 and 252.83±50.47mg/dL at 100 mg/kg and 200 mg/kg doses of O. albiflora, respectively, when compared to the isotonic saline solution control group, eliciting a blood glucose level of 494.20±27.32. Among the tested standard compounds, rutin and isoquercetin were detected in the examined species. The highest amount of rutin (1.1981±0.0017%) and isoquercetin (0.7318±0.0197%) were found in O. albiflora and O. argyrea subsp. argyrea, respectively. Antidiabetic activities of the tested Onobrychis species seem to indicate a possible correlation with their rutin and isoquercetin contents. Therefore, rutin and isoquercetin may be the antidiabetic compounds that contribute to the antidiabetic activity of the tested Onobrychis species.


Subject(s)
Plant Extracts/analysis , Hypoglycemic Agents/pharmacology , Fabaceae/adverse effects , Rutin/analysis , Chromatography, High Pressure Liquid/methods , Alloxan/adverse effects
11.
Einstein (Säo Paulo) ; 17(3): eAO4635, 2019. tab, graf
Article in English | LILACS | ID: biblio-1012003

ABSTRACT

ABSTRACT Objective: To investigate the anti-hyperglycemic effects of Plathymenia reticulata hydroalcoholic extract and related changes in body weight, lipid profile and the pancreas. Methods: Diabetes was induced in 75 adult male Wistar rats via oral gavage of 65mg/Kg of streptozotocin. Rats were allocated to one of 8 groups, as follows: diabetic and control rats treated with water, diabetic and control rats treated with 100mg/kg or 200mg/kg of plant extract, and diabetic and control rats treated with glyburide. Treatment consisted of oral gavage for 30 days. Blood glucose levels and body weight were measured weekly. Animals were sacrificed and lipid profile and pancreatic tissue samples analyzed. Statistical analysis consisted of ANOVA, post-hoc Tukey-Kramer, paired Student's t and χ2 tests; the level of significance was set at 5%. Results: Extract gavage at 100mg/kg led to a decrease in blood glucose levels in diabetic rats in the second, third (198.71±65.27 versus 428.00±15.25) and fourth weeks (253.29±47.37 versus 443.22±42.72), body weight loss (13.22±5.70 versus 109.60±9.95) and lower cholesterol levels (58.75±3.13 versus 80.11±4.01) in control rats. Extract gavage at 200mg/Kg led to a decrease in glucose levels on the fourth week in diabetic rats, body weight loss in the second, third and fourth weeks in control rats, and lower cholesterol levels in diabetic and control rats. Islet hyperplasia (p=0.005) and pancreatic duct dilation (p=0.047) were observed in diabetic and control rats. Conclusion: Plathymenia extract reduced blood glucose levels in diabetic rats, and body weight in control rats, and promoted pancreatic islet hyperplasia in diabetic and control rats.


RESUMO Objetivo: Avaliar o efeito anti-hiperglicêmico do extrato hidroalcoólico de Plathymenia reticulata, alterações no peso, lipídeos e efeito sobre o pâncreas. Métodos: O diabetes foi induzido pela administração de estreptozotocina 65mg/kg, em 75 ratos Wistar adultos machos, divididos em 8 grupos diferentes: ratos diabéticos e controle + água, ratos diabéticos e controle + 100mg/kg ou 200mg/kg de extrato, ratos diabéticos e controle + gliburida. O tratamento foi realizado por gavagem (oral) por 30 dias. Níveis de glicose e peso foram verificados semanalmente. Os animais foram sacrificados, e amostras de lipídeos e do pâncreas foram analisadas. A análise estatística incluiu ANOVA, post-hoc Tukey-Kramer, teste t de Student pareado e teste do χ2, com nível de significância de 5%. Resultados: O extrato 100mg/kg promoveu redução nos níveis de glicose sanguínea em ratos diabéticos na segunda, terceira (198,71±65,27 versus 428,00±15,25) e quarta semanas (253,29±47,37 versus 443,22±42,72), perda de peso (13,22±5,70 versus 109,60±9,95) e diminuição do colesterol (58,75±3,13 versus 80,11±4,01) em ratos controle. Com extrato de 200mg/kg, houve redução dos níveis de glicose na quarta semana, nos ratos diabéticos; de peso na segunda, terceira e quarta semanas, nos ratos controle; e de colesterol nos animais diabéticos e controle. Ocorreram hiperplasia de ilhotas (p=0,005) e dilatação dos ductos pancreáticos (p=0,047) em ratos diabéticos e controles. Conclusão: O extrato de Plathymenia reduziu os níveis de glicose em ratos diabéticos e de peso em ratos controle, além de ter promovido hiperplasia de ilhotas pancreáticas em diabéticos e controles.


Subject(s)
Animals , Male , Rats , Plant Extracts/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/pharmacology , Fabaceae , Blood Glucose/analysis , Body Weight/drug effects , Cholesterol , Rats, Wistar , Streptozocin , Plant Leaves , Diabetes Mellitus, Experimental/chemically induced , Disease Models, Animal , Hyperplasia/pathology , Phytotherapy
12.
Arq. bras. cardiol ; 111(2): 162-169, Aug. 2018. graf
Article in English | LILACS | ID: biblio-950215

ABSTRACT

Abstract Background: Pioglitazone has been widely used as an insulin-sensitizing agent for improving glycemic control in patients with type 2 diabetes mellitus. However, cardiovascular risk and protective effects of pioglitazone remain controversial. Objectives: In this study, we investigated whether pioglitazone affects cardiomyocyte apoptosis and hypertrophy by regulating the VEGFR-2 signaling pathway. Methods: Cardiomyocytes were enzymatically isolated from 1- to 3-day-old Sprague-Dawley rat ventricles. Effects of pioglitazone and the VEGFR-2-selective inhibitor apatinib on cardiomyocyte apoptotic rate was determined using flow cytometry, and hypertrophy was evaluated using [3H]-leucine incorporation. The protein expressions of unphosphorylated and phosphorylated VEGFR-2, Akt, P53, and mTOR were determined by Western-Blotting. Analysis of variance (ANOVA) was used to assess the differences between groups. Results: Pioglitazone and VEGFR-2-selective inhibitor apatinib reduced rat cardiomyocyte viability and cardiomyocyte hypertrophy induced by angiotensin II in vitro. Furthermore, in the same in vitro model, pioglitazone and apatinib significantly increased the expression of Bax and phosphorylated P53 and decreased the expression of phosphorylated VEGFR-2, Akt, and mTOR, which promote cardiomyocyte hypertrophy. Conclusions: These findings indicate that pioglitazone induces cardiomyocyte apoptosis and inhibits cardiomyocyte hypertrophy by modulating the VEGFR-2 signaling pathway.


Resumo Fundamento: A pioglitazona tem sido amplamente utilizada como droga sensibilizadora da insulina para melhorar o controle glicêmico em pacientes com diabetes mellitus tipo 2. No entanto, o risco cardiovascular bem como os efeitos protetores da pioglitazona ainda são controversos. Objetivos: Neste estudo, investigamos se os efeitos da pioglitazona sobre a apoptose e a hipertrofia de cardiomiócitos ocorrem via regulação da via de sinalização do VEGFR-2. Métodos: os cardiomiócitos foram isolados enzimaticamente dos ventrículos de ratos Sprague-Dawley de 1-3 anos de vida. Os efeitos da pioglitazona e do inibidor seletivo de VEGFR-2 apatinib sobre a taxa de apoptose dos cardiomiócitos foram avaliados por citometria de fluxo, e a hipertrofia avaliada por incorporação de leucina-[3H]. As expressões de VEGFR-2, Akt, P53, e mTOR fosforiladas e não fosforiladas foram determinadas por Western Blotting. Análise de variância (ANOVA) foi usada para avaliar diferenças entre os grupos. Resultados: a pioglitazona e o apatinib reduziram a viabilidade e a hipertrofia de cardiomiócitos induzida por angiotensina II in vitro. Além disso, no mesmo modelo in vitro, a pioglitazona e o apatinib aumentaram significativamente a expressão de Bax e P53 fosforilada, e diminuiu a expressão de VEGFR-2, Akt, e mTOR, que promove hipertrofia de cardiomiócitos. Conclusões: Esses resultados indicam que a pioglitazona induz a apoptose e inibe a hipertrofia de cardiomiócitos pela modulação da via de sinalização de VEGFR-2.


Subject(s)
Animals , Rats , Apoptosis/drug effects , Vascular Endothelial Growth Factor Receptor-2/drug effects , Thiazolidinediones/pharmacology , Hypoglycemic Agents/pharmacology , Signal Transduction/drug effects , Rats, Sprague-Dawley , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/pathology , Pioglitazone , Hypertrophy/chemically induced , Hypertrophy/pathology , Animals, Newborn
13.
Braz. J. Pharm. Sci. (Online) ; 54(2): e17467, 2018. tab, graf
Article in English | LILACS | ID: biblio-951941

ABSTRACT

ABSTRACT The leaves of Acacia modesta Wall. have been shown to possess diverse pharmacological properties. Therefore, we aimed at evaluating anti-diabetic, cytotoxic and proliferative effects of extracts of Acacia modesta Wall. leaves. After evaluating the primary and secondary metabolites, anti-diabetic activity of various extracts was assessed by α-amylase inhibition, glucose uptake by yeast cells and non-enzymatic glycosylation of hemoglobin assay. Cytotoxicity and proliferative potential was assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and short term proliferation assays, respectively, using human liver carcinoma cell line, HepG2. Among other extracts, chloroform extract exhibited 34.16% inhibition of α-amylase, 90.65% inhibition of hemoglobin glycosylation and 94.75% glucose uptake employing α-amylase inhibition, non-enzymatic glycosylation of hemoglobin and glucose uptake by yeast cells assays, respectively. Moreover, extracts exhibited no significant effects on HepG2 cell viability and proliferation. So, this data suggested that chloroform extract of leaves of Acacia modesta Wall., exhibited higher anti-hyperglycemic activity in comparison to extracts in other solvents, while no extract demonstrated cytotoxic and proliferation effects when tested using HepG2 cell line


Subject(s)
Plant Leaves/classification , Acacia/adverse effects , In Vitro Techniques , Plant Extracts/analysis , Hypoglycemic Agents/pharmacology
14.
Braz. j. med. biol. res ; 51(4): e6980, 2018. graf
Article in English | LILACS | ID: biblio-889067

ABSTRACT

Hormones regulate hepatic gene expressions to maintain metabolic homeostasis. Ectonucleotide pyrophosphatase/phosphodiesterase 1 has been thought to interfere with insulin signaling. To determine its potential role in the regulation of metabolism, we analyzed its gene (Enpp1) expression in the liver of rats experiencing fasting and refeeding cycles, and in primary rat hepatocytes and human hepatoma HepG2 cells treated with insulin and dexamethasone using northern blot and real-time PCR techniques. Hepatic Enpp1 expression was induced by fasting and reduced by refeeding in the rat liver. In primary rat hepatocytes and HepG2 hepatoma cells, insulin reduced Enpp1 mRNA abundance, whereas dexamethasone induced it. Dexamethasone disrupted the insulin-reduced Enpp1 expression in primary hepatocytes. This is in contrast to the responses of the expression of the cytosolic form of phosphoenolpyruvate carboxykinase gene to the same hormones, where insulin reduced it significantly in the process. In addition, the dexamethasone-induced Enpp1 gene expression was attenuated in the presence of 8-Br-cAMP. In conclusion, we demonstrated for the first time that hepatic Enpp1 is regulated in the cycle of fasting and refeeding, a process that might be attributed to insulin-reduced Enpp1 expression. This insulin-reduced Enpp1 expression might play a role in the development of complications in diabetic patients.


Subject(s)
Humans , Animals , Male , Rats , Pyrophosphatases/genetics , RNA, Messenger/drug effects , Dexamethasone/pharmacology , Phosphoric Diester Hydrolases/genetics , Glucocorticoids/pharmacology , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Liver/enzymology , Pyrophosphatases/biosynthesis , Pyrophosphatases/drug effects , Insulin Resistance , RNA, Messenger/metabolism , Gene Expression Regulation, Enzymologic/drug effects , Enzyme Induction/drug effects , Fasting/metabolism , Rats, Sprague-Dawley , Phosphoric Diester Hydrolases/biosynthesis , Phosphoric Diester Hydrolases/drug effects , Hep G2 Cells , Real-Time Polymerase Chain Reaction
15.
An. acad. bras. ciênc ; 89(3): 1699-1705, July-Sept. 2017. graf
Article in English | LILACS | ID: biblio-886771

ABSTRACT

ABSTRACT Introduction/Aim: The gut has shown to have a pivotal role on the pathophysiology of metabolic disease. Food stimulation of distal intestinal segments promotes enterohormones secretion influencing insulin metabolism. In diabetic rats, oral insulin has potential to change intestinal epithelium behavior. This macromolecule promotes positive effects on laboratorial metabolic parameters and decreases diabetic intestinal hypertrophy. This study aims to test if oral insulin can influence metabolic parameters and intestinal weight in obese non-diabetic rats. Methods: Twelve weeks old Wistar rats were divided in 3 groups: control (CTRL) standard chow group; high fat diet low carbohydrates group (HFD) and HFD plus daily oral 20U insulin gavage (HFD+INS). Weight and food consumption were weekly obtained. After eight weeks, fasting blood samples were collected for laboratorial analysis. After euthanasia gut samples were isolated. Results: Rat oral insulin treatment decreased body weight gain (p<0,001), fasting glucose and triglycerides serum levels (p<0,05) an increased intestinal weight of distal ileum (P<0,05). Animal submitted to high fat diet presented higher levels of HOMA-IR although significant difference to CT was not achieved. HOMA-beta were significantly higher (p<0.05) in HFD+INS. Visceral fat was 10% lower in HFD+INS but the difference was not significant. Conclusions: In non-diabetic obese rats, oral insulin improves metabolic malfunction associated to rescue of beta-cell activity.


Subject(s)
Animals , Male , Rats , Blood Glucose/analysis , Weight Loss/drug effects , Diet, High-Fat , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Lipids/blood , Blood Glucose/drug effects , Radioimmunoassay , Rats, Wistar , Hypoglycemic Agents/pharmacology , Insulin/pharmacology
16.
An. acad. bras. ciênc ; 89(1): 317-331, Jan,-Mar. 2017. tab, graf
Article in English | LILACS | ID: biblio-886626

ABSTRACT

ABSTRACT Mansoa hirsuta (Bignoniaceae) is a native plant from caatinga in Brazilian semiarid. This plant has been locally used as antimicrobial and hypoglycemiant agents, but their action mechanisms and toxicity remain largely unknown. Therefore, we evaluated the composition and antioxidant, cytoprotective and hypoglycemiant effects of raw extract, fractions and compounds from leaves of M. hirsuta. The cytogenotoxic effects of ursolic and oleanolic acids, the main phytotherapic components of this plant, were assessed. The raw extract and fractions presented steroids, saponins, flavonols, flavanonols, flavanones, xanthones, phenols, tannins, anthocyanins, anthocyanidins and flavonoids. The ethyl acetate fraction inhibited efficiently the cascade of lipid peroxidation while the hydroalcoholic fraction was richer in total phenols and more efficient in capturing 2,2-diphenyl-1-picrylhydrazyl (·DPPH) and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS·+) radicals. The isolated fraction of M. hirsuta also inhibited the α-amylase activity. Cytotoxic effects were absent in both raw extract and fractions while ursolic+oleanolic acids were efficient in protecting cells after exposure to hydrogen peroxide. Moreover, this mixture of acid shad no significant interference on the mitotic index and frequency of nuclear and/or chromosomal abnormalities in Allium cepa test. Therefore, M. hirsuta represents a potential source of phytochemicals against inflammatory and oxidative pathologies, including diabetes.


Subject(s)
Animals , Plant Extracts/pharmacology , Bignoniaceae/chemistry , Hypoglycemic Agents/pharmacology , Antioxidants/pharmacology , Reference Values , Triterpenes/chemistry , Brazil , Cell Survival/drug effects , Cells, Cultured , Reproducibility of Results , Cricetinae , Plant Leaves/chemistry , Onions/drug effects , Cytoprotection , Ethanol/chemistry , alpha-Amylases/chemistry , Fibroblasts/drug effects , Hypoglycemic Agents/isolation & purification , Antioxidants/isolation & purification
17.
An. acad. bras. ciênc ; 89(1): 263-272, Jan,-Mar. 2017. tab, graf
Article in English | LILACS | ID: biblio-886644

ABSTRACT

ABSTRACT Bauhinia holophylla, commonly known as "cow's hoof", is widely used in Brazilian folk medicine for the diabetes treatment. Therefore, the aim of this study was at evaluating the aqueous extract effect of Bauhinia holophylla leaves treatment on the streptozotocin-induced diabetic rats. Diabetes was induced by Streptozotocin (40 mg/Kg) in female Wistar rats. Oral administration of aqueous extract of Bauhinia holophylla leaves was given to non-diabetic and diabetic rats at a dose of 400 mg/kg during 21 days. On day 17 of treatment, the Oral Glucose Tolerance Test was performed to determine the area under the curve. At the end of the treatment, the animals were anesthetized and blood was collected for serum biochemical parameters analysis. After treatment with Bauhinia holophylla extract, non-diabetic and diabetic rats presented no glycemic changes. On the other hand, the plant treatment decreased body weight and increased ALT and AST activities. In conclusion, the treatment with aqueous extract of B. holophylla leaves given to diabetic rats presented no hypoglycemic effect in nondiabetic animals and no antidiabetic effect in diabetic animals with the doses studied. In addition, the diabetic animals treated with the B. holophylla extract showed inconvenient effects and its indiscriminate consumption requires particular carefulness.


Subject(s)
Animals , Female , Plant Extracts/therapeutic use , Bauhinia/chemistry , Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/therapeutic use , Time Factors , Blood Glucose/analysis , Blood Glucose/drug effects , Body Weight , Plant Extracts/pharmacology , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Streptozocin , Plant Leaves/chemistry , Drinking , Eating , Glucose Tolerance Test , Hypoglycemic Agents/pharmacology
18.
Rev. bras. enferm ; 70(1): 7-14, jan.-fev. 2017. tab, graf
Article in Portuguese | LILACS, BDENF | ID: biblio-843603

ABSTRACT

RESUMO Objetivo: descrever o processo de construção de uma cartilha educativa sobre insulinoterapia para crianças com diabetes mellitus tipo 1. Método: abordagem metodológica, na qual se seguiram as etapas: seleção do conteúdo e tipo de tecnologia a ser construída (para essa etapa, foi realizada revisão integrativa, análises dos comentários de blogs sobre Diabetes Mellitus tipo 1 e entrevista com as crianças), criação de imagens, diagramação e composição do layout. Resultados: o trabalho resultou na produção da versão final da cartilha educativa, que teve como título Aplicando a insulina: a aventura de Beto. O processo de construção da cartilha foi embasado na participação ativa das crianças e norteado pelo referencial teórico do Construtivismo Piagetiano. Conclusão: o recurso é facilitador para a melhoria do conhecimento e das práticas de autocuidado de crianças com Diabetes Mellitus tipo 1.


RESUMEN Objetivo: describir el proceso de construcción de una cartilla educativa sobre insulinoterapia para niños con diabetes mellitus tipo 1. Método: abordaje metodológico en el que unas etapas fueron seguidas: selección de contenido y tipo de tecnología a ser construida (para esa etapa, se realizó una revisión integrativa, análisis de comentarios de blogs sobre Diabetes Mellitus tipo 1 y entrevista con los niños), creación de imágenes, diagramación y composición de layout. Resultados: el trabajo resultó en la producción de una versión final de una cartilla educativa, cuyo título fue Aplicando la insulina: la aventura de Beto. El proceso de construcción de la cartilla se basó en la participación activa de los niños y se norteó por el referencial teórico del Constructivismo Piagetiano. Conclusión: el recurso es facilitador para la mejoría del conocimiento y de las prácticas de autocuidado de niños con Diabetes Mellitus tipo 1.


ABSTRACT Objective: to describe the process of developing of an educational booklet on insulin therapy for children with diabetes mellitus type 1. Method: methodological approach, in which the following steps were carried out: selecting of the content and type of technology to be developed (for this step, an integrative review, an analysis of the comments of blogs about Diabetes Mellitus type 1 and interviews with the children were performed), creation of images, formatting and layout composition. Results: the work resulted in the production of the final version of the educational booklet, which was titled Aplicando a insulina: a aventura de Beto [Applying insulin: Beto's adventure]. The process of developing of the booklet was based on the active participation of the children and guided by the theoretical framework of Piagetian Constructivism. Conclusion: the resource is a facilitator for the improvement of the knowledge and practices of self care of children with Diabetes Mellitus type 1.


Subject(s)
Humans , Child, Preschool , Child , Adolescent , Pamphlets , Self Care/methods , Patient Education as Topic/methods , Program Development/methods , Diabetes Mellitus, Type 1/drug therapy , Hyperglycemia/drug therapy , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/pharmacology , Insulin/therapeutic use , Insulin/pharmacology
19.
Biol. Res ; 50: 9, 2017. tab, graf
Article in English | LILACS | ID: biblio-838964

ABSTRACT

BACKGROUND: A number of dysregulated miRNAs have been identified and are proposed to have significant roles in the pathogenesis of type 2 diabetes mellitus or renal pathology. Alpinia oxyphylla has shown significant anti-inflammatory properties and play an anti-diabetes role. The objective of this study was to detect the alteration of miRNAs underlying the anti-diabetes effects of A. oxyphylla extract (AOE) in a type II diabetic animal model (C57BIKsj db-/db-). RESULTS: Treatment with AOE for 8 weeks led to lower concentrations of blood glucose, urine albumin, and urine creatinine. 17 and 13 miRNAs were statistically identified as differentially regulated in the DB/DB and db-/db- AOE mice, respectively, compared to the untreated db-/db- mice. Of these, 7 miRNAs were identified in both comparison groups, and these 7 miRNAs were verified by quantitative real-time PCR. Functional bioinformatics showed that the putative target genes of 7 miRNAs were associated with several diabetes effects and signaling pathways. CONCLUSIONS: These founding suggest that the potential of AOE as a medicinal anti-diabetes treatment through changes in the expressions of specific miRNAs. The results provide a useful resource for future investigation of the role of AOE-regulated miRNAs in diabetes mellitus.


Subject(s)
Animals , Male , Mice , Plant Extracts/pharmacology , MicroRNAs/drug effects , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/pharmacology , Kidney/drug effects , Time Factors , Blood Glucose/analysis , Gene Expression Regulation , Reproducibility of Results , Treatment Outcome , Sequence Analysis, RNA , Creatinine/blood , MicroRNAs/metabolism , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/metabolism , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/drug therapy , Albuminuria , Real-Time Polymerase Chain Reaction , Kidney/metabolism , Mice, Inbred C57BL
20.
Pakistan Journal of Pharmaceutical Sciences. 2017; 30 (1): 171-178
in English | IMEMR | ID: emr-185755

ABSTRACT

To investigate the antihyperglycemic and antioxidant activity of the total flavones of Potentilla kleiniana Wight et Arn. [TFP] in streptozotocin [STZ] induced diabetic rats. STZ-induced diabetic rats were treated with TFP weekly for 4 weeks at three doses [100 mg/kg, 200 mg/kg and 400 mg/kg]. Blood glucose levels [BGL], body weight, insulin, total cholesterol [TC], triglyceride [TG], high density lipoprotein [HDL], very low density lipoprotein [VLDL], low density lipoprotein [LDL], malondialdehyde [MDA], glutathione [GSH], super oxide dismutase [SOD] and catalase [CAT] levels of liver and pancreas were measured weekly for 4 weeks. STZ administration resulted in oxidative damage of pancreas, then hyperglycemia proved by higher MDA, lower insulin and higher BGL in comparison to normal rats. TC, TG, LDL and VLDL cholesterol levels were also significantly elevated with decreased GSH, SOD, and CAT levels. A steady decrease in BGL and increase in insulin level were observed 4 weeks after TFP treatment in a dose dependent manner, as well as remarkable improvement in body weight and biochemical parameters. TFP have the effect of inhibiting hyperglycemia and oxidative stress, and the administration may be helpful in the prevention of diabetic complications associated with oxidative stress


Subject(s)
Animals, Laboratory , Male , Streptozocin , Hypoglycemic Agents/pharmacology , Antioxidants/pharmacology , Phytotherapy , Plants, Medicinal , Rats, Wistar
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