Inhibition of α-Glycosidase by Lippia dulcis Trevir. (Verbenaceae) Preparations, Quantification of Verbascoside, and Study of Its Molecular Docking.

This study aimed to quantify verbascoside (VEB), perform molecular docking studies of VEB with the α-glucosidase (GL) of Bacillus stearothermophilus, and evaluate the inhibition of the enzyme by L. dulcis preparations. The substrate concentration and presence of reduced glutathione were evaluated for their effect on the in vitro inhibition of the GL enzyme. Assays were also performed in the presence and absence of simulated gastric fluid. The antidiabetic fractions 2 and 3 were the most inhibited GL, but their activity were significantly decreased in the presence of gastric fluid. Chromatographic analyses confirmed the predominant presence of VEB in the samples. The samples had VEB concentrations between 49.9 and 243.5 mg/g. Simulation of the molecular docking of VEB were consistent with its GL-inhibitory activity. It can conclude that the crude ethanol extract and fractions show inhibitory activity against the GL enzyme.

An Insulin Receptor-Binding Multifunctional Protein from Tamarindus indica L. Presents a Hypoglycemic Effect in a Diet-Induced Type 2 Diabetes-Preclinical Study.

The objectives of this study were to evaluate the hypoglycemic effect of the trypsin inhibitor isolated from tamarind seeds (TTI) in an experimental model of T2DM and the in silico interaction between the conformational models of TTI 56/287 and the insulin receptor (IR). After inducing T2DM, 15 male Wistar rats were randomly allocated in three groups (n = 5): 1-T2DM group without treatment; 2-T2DM group treated with adequate diet; and 3-T2DM treated with TTI (25 mg/kg), for 10 days. Insulinemia and fasting glucose were analyzed, and the HOMA-IR and HOMA-ß were calculated. The group of animals treated with TTI presented both lower fasting glucose concentrations (p = 0.0031) and lower HOMA-IR indexes (p = 0.0432), along with higher HOMA-ß indexes (p = 0.0052), than the animals in the other groups. The in silico analyses showed that there was an interaction between TTIp 56/287 and IR with interaction potential energy (IPE) of -1591.54 kJ mol-1 (±234.90), being lower than that presented by insulin and IR: -894.98 kJ mol-1 (±32.16). In addition, the presence of amino acids, type of binding and place of interaction other than insulin were identified. This study revealed the hypoglycemic effect of a bioactive molecule of protein origin from Tamarind seeds in a preclinical model of T2DM. Furthermore, the in silico analysis allowed the prediction of its binding in the IR, raising a new perspective for explaining TTI's action on the glycemic response.

Atividade antidiabética de Syzygium cumini l. ­ uma revisão sistemática / Antidiabetic activity of Syzygium cumini l. - a systematic review

RESUMO: Introdução- O Diabetes Mellitus (DM) é um distúrbio metabólico caracterizado por hiperglicemia, devido a uma deficiência de secreção de insulina, à diminuição da sensibilidade à insulina e/ou ambos. Trata-se de uma doença comum e crescente que apresenta alta morbimortalidade, com perda importante na qualidade de vida, além de grande impacto econômico e social nos serviços de saúde. Apesar das várias opções de fármacos sintéticos disponíveis para o seu tratamento, com a frequência e gravidade dos efeitos colaterais, se faz necessário a busca por novas alternativas terapêuticas. As plantas medicinais podem ser utilizadas como medicina alternativa, por se tratar de uma terapia de baixo custo de aquisição, além de menor incidência de efeitos colaterais e maior acesso pela população. A planta Syzygium cumini, conhecida popularmente como jambolão, possui propriedades antidiabéticas que vêm sendo estudadas através de ensaios pré-clínicos e clínicos em comparação com tratamentos convencionais. Além disso, essa busca traz apoio à pesquisa botânica, desenvolvimento tecnológico e diversidade biológica. Portanto, a presente revisão teve como objetivo reunir estudos semelhantes sobre a atividade antidiabética da Syzygium cumini L. e avaliá-los criticamente segundo sua metodologia elucidando sua utilização como antidiabético. Metodologia- Estudo de revisão sistemática da literatura de ensaios préclínicos e clínicos, através das bases de dados Medline, LILACS, Web of Science e Embase, a partir do ano de 2010 até o ano de 2021. Dentre os 15 estudos incluídos na revisão, 13 são ensaios pré-clínicos e 2 ensaios clínicos. Resultados- Nos estudos selecionados observou-se redução considerável da glicemia, hemoglobina glicada, resistência à insulina e aumento da insulina sérica, em comparação com grupos placebo e fármacos convencionais, com valor de P estatisticamente significante (P<0,05). Discussão- A dose administrada da planta variou de 20 miligramas por quilo de peso corporal por dia a 1,25 gramas por quilo de peso corporal por dia nos ensaios pré- clínicos; e 10 gramas por dia nos ensaios clínicos; e de maneira geral, os resultados de efeito hipoglicêmico foram dependentes da dose administrada. Ainda em relação à administração, a planta foi administrada em forma de pó, extrato aquoso, extrato etanólico, fração de acetato de etila e dieta nutracêutica. Já o tempo de tratamento variou de 1 (dose única) a 90 dias. O mecanismo de ação é proposto, porém não conclusivo. Conclusão- Tendo em vista o exposto na revisão, compreende-se que a planta Syzygium cumini L. possui atividade antidiabética, podendo ser utilizado como um potente e custo eficaz coadjuvante no tratamento do Diabetes mellitus, sendo necessário mais estudos clínicos para elucidação de sua ação terapêutica em seres humanos.

Introduction- Diabetes mellitus is a metabolic disorder characterized by hyperglycemia, due to insulin secretion deficiency, decreased insulin sensitivity and/or both. It is a common and growing disease that has high morbidity and mortality with significant loss in quality of life, in addition to a great economic and social impact on health services. Besides the various options of synthetic drugs available for treatment, with the frequency and severity of side effects, it is necessary to search for new therapeutic alternatives. Medicinal plants can be used as an alternative medicine because it is a low-cost acquisition therapy, in addition to a lower incidence of side effects and greater access by the population. The plant Syzygium cumini popularly known as Jambolão has antidiabetic properties have been studied through pre-clinical and clinical trials compared to conventional treatments. In addition, this search supports botanical research, technological development and biological diversity. Therefore, the present review aimed to bring similar studies on the antidiabetic activity of Syzygium cumini L. and evaluate them critically according to their methodology, elucidating their use as antidiabetic. Method- Systematic review study of the literature of pre-clinical and clinical trials through the databases Medline, LILACS, Web of Science and Embase, from 2010 to 2021. Among the 15 studies included in the review, 13 are pre-clinical trials and 2 clinical trials. Results- In the selected studies, a considerable reduction in blood glucose, glycated hemoglobin, insulin resistance and increased insulin was observed, compared to placebo groups and conventional drugs, with a statistically P value (P<0.05). Discussion- In preclinical trials, the plant's administered dose ranged from 20 milligrams per kilogram of body weight per day to 1.25 grams per kilogram of body weight per day; in clinical trials, the administered dose ranged from 10 grams per day to 20 milligrams per kilogram of body weight per day; and in general, the hypoglycemic effect was dependent on the administered dose. In terms of administration, the plant was given in powder form, aqueous extract, ethanol extract, ethyl acetate fraction, and a nutraceutical diet. The duration of treatment varies from one (single dose) to ninety days. The action mechanism is suggested, but not proven. Conclusion- Based on the findings of the review,it is believed that the plant Syzygium cumini L. has antidiabetic activity and could be used as a potent, safe, and cost-effective adjuvant in the treatment of diabetes mellitus, though more clinical research is needed to fully understand its therapeutic action in humans.

Vanadium(IV)-diamine complex with hypoglycemic activity and a reduction in testicular atrophy.

The insulin enhancing activity, histological analysis and, testicular degeneration by a VIVO-complex containing the 2,2'-(ethane-1,2-diylbis(azanediyl))diethanolate ligand, VOIV(C6H14N2O2-κ2N,κ2O), abbreviated VIVO(BHED), were investigated in diabetic male Wistar rats. The complex was administered by oral gavage of freshly prepared solutions of vanadium complex. Biological studies demonstrated that the vanadium complex normalized the elevated glucose levels in male Wistar rats with streptozotocin-induced diabetes and these compounds also avoided common responses in diabetic animals such as weight loss and reduction in the size of the epididymis, prostate, testis and seminal gland. The 51V NMR and EPR studies showed the formation of VIVO(BHED) and the oxidation product [VVO2BHED]- with two possible decomposition pathways. In summary, these studies demonstrate that the VIVO(BHED) complex or its decomposition products show similar effects as insulin in decreasing elevated blood glucose levels.

Insulin-Like Proteins in Plant Sources: A Systematic Review.

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia. Proteins in plant sources that enable the maintenance of the glycemic profile may be of interest in the context of T2DM. However, their mechanisms of action are unclear, unlike other bioactive compounds. This systematic review identified and described the mechanisms of action of isolated and purified proteins and peptides extracted from vegetables on the reduction of blood glucose in T2DM in experimental studies. The research was done in PubMed, ScienceDirect, Scopus, Web of Science, Embase and Virtual Health Library (VHL) databases in March 2019. The initial search retrieved 916 articles, and, after reading the title, abstract and keywords, 24 articles were eligible for full reading. Then, five articles were eligible to build this systematic review. The evaluation of the evidence and the strength of the recommendations of the studies was evaluated with the SYstematic Review Center for Laboratory animal Experimentation - SYRCLE. Studies with proteins or peptides extracted from soybean (Glycine max), corn (Zea mays), peas (Pisum sativum), costus (Costus igneus) and ginseng (Panax ginseng) were found, and all of them decreased glycemia but not by the same mechanisms. The mechanism of action of proteins extracted from Glycine max, Pisum sativum, Costus igneus were similar, acting in the insulin-mediated pathways. The peptide derived from Zea mays increased GLP-1 expression, and the peptide from Panax ginseng reduced NF-kB signaling, both resulting in stimulating the release of insulin. Therefore, bioactive proteins and peptides of plant sources act through biochemical pathways, in the modulation of insulin resistance and the hyperglycemic state. These compounds are promising in scientific research on T2DM, because there is a probable similarity of these proteins with insulin, which enables them to act as insulin-like molecules.

Beetle (Ulomoides dermestoides) fat improves diabetes: effect on liver and pancreatic architecture and on PPARgamma expression

Ulomoides dermestoides is a beetle traditionally consumed to treat diabetes. In this study, we performed a composition analysis of U. dermestoides to obtain the principal fractions, which were used to assess the effect on glycemia, liver and pancreatic architecture, and PPARγ and GLUT4 expression. Normal mice and alloxan-induced diabetic mice were administered fractions of chitin, protein or fat, and the acute hypoglycemic effect was evaluated. A subacute study involving daily administration of these fractions to diabetic mice was also performed over 30 days, after which the liver and pancreas were processed by conventional histological techniques and stained with hematoxylin and eosin to evaluate morphological changes. The most active fraction, the fat fraction, was analyzed by gas chromatography-mass spectrometry (GC-MS), and PPARγ and GLUT4 mRNA expressions were determined in 3T3-L1 adipocytes. The protein and fat fractions exhibited hypoglycemic effects in the acute as well as in the 30-day study. Only the fat fraction led to elevated insulin levels and reduced glycemia, as well as lower intake of water and food. In the liver, we observed recovery of close hepatic cords in the central lobule vein following treatment with the fat fraction, while in the pancreas there was an increased density and percentage of islets and number of cells per islet, suggesting cellular regeneration. The GC-MS analysis of fat revealed three fatty acids as the major components. Finally, increased expression of PPARγ and GLUT4 was observed in 3T3-L1 adipocytes, indicating an antidiabetic effect.

Caracterização do fármaco hipoglicemiante glibenclamida / Characterization of the hypoglycemic drug glibenclamide

A glibenclamida (GLIB) é um fármaco de segunda geração, administrado por via oral na forma de comprimidos, utilizado para o tratamento de Diabetes mellitus. GLIB possui baixa solubilidade aquosa, o que pode levar a uma baixa liberação a partir de formas farmacêuticas sólidas no teste de dissolução e, portanto, a variabilidades no tratamento. Neste estudo, avaliam-se as características da matéria-prima GLIB, que podem influenciar o perfil de dissolução, e conseqüentemente, a biodisponibilidade, por meio de técnicas tais como, adsorção de nitrogênio, difração de raio laser, análise térmica, espectroscopia por IV/UV e difração de raios X.

Glibenclamide (GLIB) or glyburide, a second-generation hypoglycemic agent is orally used in the form of tablets for the treatment of diabetes mellitus. Bulk GLIB has a low aqueous solubility and it may yield low drug release in the dissolution test, causing variabilility in the treatment. This work evaluates the bulk GLIB features, which may influence drug release profile, hence, bioavailability, by means of techniques such as nitrogen sorption analysis, laser diffraction, thermal analysis, IV/UV spectroscopy and X-ray analysis.

Teste de dissolução para avaliação de liberação de glibenclamida em comprimidos / Glibenclamide dissolution test for drug release evaluation in tablets

A glibenclamida (GLIB) ou gliburida, é um hipoglicemiante oral de segunda geração, da classe das sulfoniluréias, usado sob a forma de comprimidos para tratamento do diabetes mellitus. Variações no tratamento podem ocorrer, devido à baixa solubilidade do fármaco em comprimidos. A comparação de várias formulações de comprimidos piloto com comprimidos do medicamento referência (Daonil®, glibenclamida 5 mg comprimidos, Aventis Pharma Ltda.) foi avaliada por meio do desenvolvimento de um teste de dissolução sem adição de solventes orgânicos ou tensoativos no meio, que mostrou ser discriminativo para as diferentes formulações farmacêuticas propostas. A quantificação de GLIB foi realizada por meio de cromatografia líquida de alta eficiência em fase reversa (CLAE-FR), método previamente validado. A partir de vários ensaios de perfil de dissolução testados comparativamente àquele de comprimidos do medicamento referência, verificou-se o potencial de determinada formulação proposta (f1 4,04 and f2 69,35) como candidata a medicamento genérico no mercado brasileiro.

Glibenclamide (GLIB) or glyburide, a second-generation hypoglycemic agent is used per oral as tablets for the treatment of diabetes mellitus. Much variabilility in the treatment may occur because of the low drug aqueous solubility in tablets dosage forms. This work reports the comparison of several pilot formulation batches with the commercial reference drug dosage form (Daonil®, glibenclamide 5 mg per tablet, Aventis Pharma Ltda.). A feasible dissolution test, developed with no use of organic solvents or surfactants in the medium, showed to be discriminative regarding to different formulations tested. GLIB quantitation was performed by a previously validated reverse-phase high performance liquid chromatography (RP-HPLC). Among several dissolution profiles compared with that of a commercial reference, a potential for a generic candidate was evident (f1 4.04 and f2 69.35) for a proposed solid dosage formulation in the Brazilian market.