RESUMO
Bioinformatics has expedited the screening of new efficient therapeutic agents for diseases such as diabetes mellitus (DM). The objective of this systematic review (SR) was to understand naturally occurring proteins and peptides studied in silico and subsequently reevaluated in vivo for treating DM, guided by the question: which peptides or proteins have been studied in silico for the treatment of diabetes mellitus? The RS protocol was registered in the International Prospective Register of Systematic Reviews database. Articles meeting the eligibility criteria were selected from the PubMed, ScienceDirect, Scopus, Web of Science, Virtual Health Library (VHL), and EMBASE databases. Five studies that investigated peptides or proteins analyzed in silico and in vivo were selected. Risk of bias assessment was conducted using the adapted Strengthening the Reporting of Empirical Simulation Studies (STRESS) tool. A diverse range of assessed proteins and/or peptides that had a natural origin were investigated in silico and corresponding in vivo reevaluation demonstrated reductions in glycemia and/or insulin, morphological enhancements in pancreatic ß cells, and alterations in the gene expression of markers associated with DM. The in silico studies outlined offer crucial insights into therapeutic strategies for DM, along with promising leads for screening novel therapeutic agents in future trials.
Assuntos
Simulação por Computador , Diabetes Mellitus , Peptídeos , Animais , Humanos , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Biologia Computacional/métodos , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/uso terapêutico , ProteínasRESUMO
PURPOSE: To assess the effect of Amorphophallus campanulatus tuber (Ac) extract in the protection of diabetic nephropathy in streptozotocin (STZ) induced diabetic nephropathy (DN) rat model. METHODS: Diabetes was induced with STZ (60 mg/kg, i.p.), and DN was confirmed after six weeks of STZ administration with the estimation of kidney function test. Further rats were treated with Ac 250 and 500 mg/kg p.o. for next four week. Oxidative stress and level of inflammatory cytokines were estimated in the kidney tissue of DN rats. Histopathology of kidney tissue was performed using hematoxylin and eosin staining. RESULTS: There was improvement in the body weight of Ac treated groups than DN group of rats. Blood glucose level was observed to be reduced in Ac treated groups than DN group on 42nd and 70th day of protocol. Treatment with Ac ameliorated the altered level of kidney function tests (creatinine and BUN), enzymes of liver function (aspartate aminotransferase and alanine aminotransferase), and lipid profile in the serum of DN rats. Oxidative stress parameters (malondialdehyde and reactive oxygen species enhances and reduction in the level of glutathione and superoxide dismutase) and inflammatory cytokines such as interleukin-6, tumour necrosis factor-α, and monocyte chemoattractant protein-1 reduces in the tissue of Ac treated group than DN group. Treatment with Ac also attenuates the altered histopathological changes in the kidney tissue of DN rats. CONCLUSIONS: The report suggests that Ac protects renal injury in DN rats by regulating inflammatory cytokines and oxidative stress.
Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Estresse Oxidativo , Extratos Vegetais , Fator de Necrose Tumoral alfa , Animais , Estresse Oxidativo/efeitos dos fármacos , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/prevenção & controle , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Masculino , Estreptozocina , Ratos , Ratos Wistar , Rim/efeitos dos fármacos , Rim/patologia , Glicemia/efeitos dos fármacos , Glicemia/análise , Modelos Animais de Doenças , Reprodutibilidade dos Testes , Tubérculos/químicaRESUMO
Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. METHODOLOGY: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. RESULTS: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. CONCLUSION: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.
Assuntos
Adipocinas , Berberina , Composição Corporal , Gymnema sylvestre , Obesidade , Resistina , Humanos , Masculino , Feminino , Adulto , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Adipocinas/sangue , Adipocinas/metabolismo , Composição Corporal/efeitos dos fármacos , Pessoa de Meia-Idade , Berberina/farmacologia , Resistina/sangue , Resistina/metabolismo , Apelina , Pressão Sanguínea/efeitos dos fármacos , Nicotinamida Fosforribosiltransferase/metabolismo , Citocinas/metabolismo , Citocinas/sangue , Extratos Vegetais/farmacologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Lectinas , Proteínas Ligadas por GPI/metabolismo , Proteínas Ligadas por GPI/genética , Fármacos Antiobesidade/farmacologia , Fármacos Antiobesidade/uso terapêuticoRESUMO
Introduction: Diabetes stands as one of the leading causes of death worldwide. Glucagon-like peptide-1 receptor agonists rank among the most effective medications for lowering blood glucose and body weight, as well as reducing cardiovascular risk in individuals with diabetes. Observational studies complement experimental evidence in new settings, different populations, and real-world healthcare practices. Methods: A multicentric observational study of adults with type 2 diabetes treated with once-weekly subcutaneous semaglutide in four health centers in Colombia was conducted. The protocol for the present study was not pre-registered. Results: Data from 186 patients were included. Most patients were women (57%) with a mean age of 62.8 ± 12.1 years. One year of once-weekly semaglutide usage was associated with a mean reduction in HbA1C of -1.47% (95% CI -1.76, -1.17), weight loss of -4.23 kg (95% CI -5.34, -3.12), and albumin/creatinine ratio of -18.6 mg/g (95% CI -60.2, -5.9). Approximately half the treated patients achieved a level of HbA1c ≤7% by the end of follow-up. Adverse events were rare and consistent with clinical trial safety profiles. Conclusion: In Colombia, administering semaglutide subcutaneously once a week over a 1-year period led to an average weight loss of 4.2 kg and a decrease of 1.4% in HbA1c.
Assuntos
Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Estudos Retrospectivos , Colômbia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/efeitos adversos , Idoso , Hemoglobinas Glicadas/análise , Glicemia/efeitos dos fármacos , Glicemia/análise , Resultado do Tratamento , Esquema de MedicaçãoRESUMO
This study aims to evaluate the phytochemical properties of Bauhinia holophylla (Bong.) Steud leaf extract, and their impact on maternal reproductive and fetal development in diabetic rats. For this, adult female Wistar rats (100 days of life) received streptozotocin (40 mg/Kg, intraperitoneal) for induction of diabetes, were mated and distributed into four groups: Nondiabetic; Nondiabetic given B. holophylla; Diabetic; and Diabetic given B. holophylla. The plant extract was given by gavage at increasing doses: 200, 400, and 800 mg/Kg. At day 21 of pregnancy, liver and blood samples were obtained for oxidative parameters and biochemical analysis, respectively. The uterus was removed for maternal-fetal outcomes. Phytochemical analysis showed a high content of phenolic components and biogenic amines. B. holophylla extract did not alter the glycemic levels but improved the lipid profile in diabetic animals. Besides that, the number of live fetuses and maternal weight gain were decreased in Diabetic group, and were not observed in animals treated. The group Diabetic treated presented a higher percentage of fetuses classified as adequate for gestational age compared to the Diabetic group. However, the treatment with plant extract caused embryo losses, fetal growth restriction, and teratogenicity in nondiabetic rats. Thus, the indiscriminate consumption requires carefulness.
Assuntos
Bauhinia , Diabetes Mellitus Experimental , Hipoglicemiantes , Extratos Vegetais , Ratos Wistar , Animais , Feminino , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Bauhinia/química , Gravidez , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Ratos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/análise , Desenvolvimento Fetal/efeitos dos fármacos , Estreptozocina , Glicemia/efeitos dos fármacos , Glicemia/análise , Folhas de Planta/químicaRESUMO
Alloxan-induced diabetic rats present with hypothyroidism. When treated with triiodothyronine (T3), glycemia and proinflammatory cytokine expression are downregulated, improving insulin sensitivity. The effectiveness of associating T3 with insulin (replacement dose [6â U] and [3â U]) in controlling glycemia was investigated in this experimental model. Male Wistar rats were made diabetic by alloxan injection and sorted into groups treated or not with insulin (3 or 6â U) associated or not with T3 (1.5 µg 100â g-1 BW) for 28 days. Nondiabetic rats constituted the control group. Fasting glycemia, glucose decay rate, and thyrotropin (TSH) were measured in the blood/serum of all animals. Immunoblotting was used to assess total GLUT4 expression in skeletal muscles and epididymal white adipose tissue. Cytokine and nuclear factor-κB (NF-κB) expression were measured in these tissues and liver. Diabetic rats presented with increased fasting glycemia, inflammatory cytokines, and NF-κB expression, TSH levels, and insulin resistance. In diabetic rats treated with T3 and/or insulin, these parameters were decreased, whereas GLUT4 and anti-inflammatory cytokine expression were increased. T3 combined with 3-U insulin restored the parameters to values of the control group and was more effective at controlling glycemia than 6-U insulin. Thus, a combination of T3 and insulin might represent a promising strategy for diabetes management since it reduces the insulin requirement by half and improves glycemic control of diabetic rats, which could postpone insulin resistance that develops with chronic insulin administration. These findings open a perspective for using thyroid analogues that provide tissue-specific effects, which might result in a potentially more effective treatment of diabetes.
Assuntos
Glicemia , Diabetes Mellitus Experimental , Transportador de Glucose Tipo 4 , Insulina , NF-kappa B , Ratos Wistar , Tri-Iodotironina , Animais , Masculino , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Tri-Iodotironina/sangue , Tri-Iodotironina/farmacologia , Ratos , Transportador de Glucose Tipo 4/metabolismo , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , NF-kappa B/metabolismo , Resistência à Insulina , Aloxano , Músculo Esquelético/metabolismo , Músculo Esquelético/efeitos dos fármacos , Tireotropina/sangue , Citocinas/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêuticoRESUMO
Type 2 diabetes mellitus (T2DM) is a major global public health concern, prompting the ongoing search for new treatment options. Medicinal plants have emerged as one such alternative. Our objective was to evaluate the antidiabetic effect of an extract from the leaves of Passiflora ligularis (P. ligularis). For this purpose, T2DM was first induced in mice using a high-fat diet and low doses of streptozotocin. Subsequently, an aqueous extract or an ethanolic extract of P. ligularis leaves was administered for 21 days. The following relevant results were found: fasting blood glucose levels were reduced by up to 41%, and by 29% after an oral glucose overload. The homeostasis model assessment of insulin resistance (HOMA-IR) was reduced by 59%. Histopathologically, better preservation of pancreatic tissue was observed. Regarding oxidative stress parameters, there was an increase of up to 48% in superoxide dismutase (SOD), an increase in catalase (CAT) activity by 35% to 80%, and a decrease in lipid peroxidation (MDA) by 35% to 80% in the liver, kidney, or pancreas. Lastly, regarding the lipid profile, triglycerides (TG) were reduced by up to 30%, total cholesterol (TC) by 35%, and low-density lipoproteins (LDL) by up to 32%, while treatments increased high-density lipoproteins (HDL) by up to 35%. With all the above, we can conclude that P. ligularis leaves showed antihyperglycemic, hypolipidemic, and antioxidant effects, making this species promising for the treatment of T2DM.
Assuntos
Glicemia , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Dieta Hiperlipídica , Hipoglicemiantes , Passiflora , Extratos Vegetais , Folhas de Planta , Animais , Folhas de Planta/química , Diabetes Mellitus Experimental/tratamento farmacológico , Extratos Vegetais/farmacologia , Hipoglicemiantes/farmacologia , Dieta Hiperlipídica/efeitos adversos , Passiflora/química , Camundongos , Masculino , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Estreptozocina , Resistência à Insulina , Pâncreas/efeitos dos fármacos , Pâncreas/patologia , Pâncreas/metabolismo , Antioxidantes/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lipídeos/sangue , FitoterapiaRESUMO
BACKGROUND: Biochemical events provoked by oxidative stress and advanced glycation may be inhibited by combining natural bioactives with classic therapeutic agents, which arise as strategies to mitigate diabetic complications. The aim of this study was to investigate whether lycopene combined with a reduced insulin dose is able to control glycemia and to oppose glycoxidative stress in kidneys of diabetic rats. METHODS: Streptozotocin-induced diabetic rats were treated with 45 mg/kg lycopene + 1 U/day insulin for 30 days. The study assessed glycemia, insulin sensitivity, lipid profile and paraoxonase 1 (PON-1) activity in plasma. Superoxide dismutase (SOD) and catalase (CAT) activities and the protein levels of advanced glycation end-product receptor 1 (AGE-R1) and glyoxalase-1 (GLO-1) in the kidneys were also investigated. RESULTS: An effective glycemic control was achieved with lycopene plus insulin, which may be attributed to improvements in insulin sensitivity. The combined therapy decreased the dyslipidemia and increased the PON-1 activity. In the kidneys, lycopene plus insulin increased the activities of SOD and CAT and the levels of AGE-R1 and GLO-1, which may be contributing to the antialbuminuric effect. CONCLUSIONS: These findings demonstrate that lycopene may aggregate favorable effects to insulin against diabetic complications resulting from glycoxidative stress.
Assuntos
Antioxidantes , Diabetes Mellitus Experimental , Produtos Finais de Glicação Avançada , Insulina , Rim , Licopeno , Estresse Oxidativo , Ratos Wistar , Animais , Licopeno/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Antioxidantes/farmacologia , Masculino , Insulina/sangue , Insulina/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Catalase/metabolismo , Arildialquilfosfatase/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Resistência à Insulina , Lactoilglutationa Liase/metabolismo , Quimioterapia Combinada , Hipoglicemiantes/farmacologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismoRESUMO
OBJECTIVE: Clinacanthus nutans (C. nutans) is a medicinal herb that most people with diabetes have historically taken. It's a diet high in antioxidants, which are supposed to help people live longer and be healthier. It is the first study to suggest using C. nutans to enhance the quality of sperm in male mice given a streptozotocin (STZ) injection. METHODS: Sixty mice were divided into two groups at the age of four weeks: group one was fed a regular diet (n=10), while group two was administered a high-fat diet (n=50) for eight weeks to develop obesity. Obese mice were given 100mg/kg of STZ to produce hyperglycemia with a 20% mortality rate. Then, 40 hyperglycemic mice were separated into two groups: STZ (n=10) and sample (n=30). The treatment groups were administered a methanolic extract of C. nutans leaves by gavage at doses of 150, 300, and 500mg/kg of body weight (n=10) for 4 weeks. RESULTS: In contrast to the STZ group, there was a substantial (p=0.001) drop in serum blood glucose and total sperm abnormalities in mice at varying doses. Catalase, glutathione s-transferase (GST), and total antioxidant capacity significantly (p=0.001) increased in the STZ mice group at varying doses, but malondialdehyde was reduced. In comparison to STZ mice, testosterone and luteinizing hormone (LH) levels improved in mice treated with extracts of C. nutans at various doses. For all of the following dependent variables, extraction of the leaf at higher concentrations of 500 milligrams/kilogram has better efficacy than 300 and 150 mg/kg after 4 weeks of treatment. CONCLUSIONS: The research and development of new natural agents to combat oxidative stress-related diseases have sparked a lot of interest. As a result, the potential leaf extract of C. nutans contains anti-hyperglycemic compounds and improves the quality of sperm in male mice.
Assuntos
Acanthaceae , Antioxidantes , Diabetes Mellitus Experimental , Extratos Vegetais , Folhas de Planta , Espermatozoides , Animais , Masculino , Camundongos , Extratos Vegetais/farmacologia , Antioxidantes/farmacologia , Espermatozoides/efeitos dos fármacos , Folhas de Planta/química , Acanthaceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Estreptozocina , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Análise do Sêmen , Estresse Oxidativo/efeitos dos fármacosRESUMO
The byproduct of Salvia hispanica (chia) seed oil extraction by cold pressing, also known as expeller, possesses a high nutritional value. It is rich in proteins, fibers, minerals, and has a residual oil content of 7-11%, which is rich in omega 3 linolenic acid (ALA). However, this byproduct has been historically undervalued. Thus, the aim of current work was to study the effects of consuming of a rich in chia expeller diet on a rabbit model of metabolically unhealthy normal weight to validate their use as a functional food. Rabbits were fed different diets for a period of 6 weeks: a standard diet (CD), a high-fat diet (HFD), a rich in expeller CD (Exp-CD) and a rich in expeller HFD (Exp-HFD). The Exp-HFD attenuated the rise in basal glucose, TyG index, triglycerides, cholesterol and non-HDL cholesterol induced by the HFD. Both rich in expeller diets reduced mean arterial blood pressure (MAP) and increase liver and fat ALA levels compared to their respective controls. Furthermore, the angiotensin converting enzyme (ACE) activity was lower in the lungs of animals fed on rich in expeller diets compared to their respective controls. In vitro studies showed that ALA inhibited ACE activity. The evaluation of vascular reactivity revealed that rich in expeller diets improved angiotensin II affinity and reduced contractile response to noradrenaline. In conclusion, the consumption of rich in expeller diets showed beneficial effects in preventing cardiovascular risk factors such as insulin resistance, dyslipidemia and MAP. Therefore, its use as functional ingredient holds significant promise.