scholarly journals Metabolic Effects of Mulberry Leaves: Exploring Potential Benefits in Type 2 Diabetes and Hyperuricemia

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
A. Hunyadi ◽  
E. Liktor-Busa ◽  
Á. Márki ◽  
A. Martins ◽  
N. Jedlinszki ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Glucose Consumption ◽  
Metabolic Effects ◽  
Bioactive Constituents ◽  
Mulberry Leaves

The leaves ofMorus albaL. have a long history in Traditional Chinese Medicine and also became valued by the ethnopharmacology of many other cultures. The worldwide known antidiabetic use of the drug has been suggested to arise from a complex combination effect of various constituents. Moreover, the drug is also a potential antihyperuricemic agent. Considering that type 2 diabetes and hyperuricemia are vice-versa in each other’s important risk factors, the use of mulberry originated phytotherapeutics might provide an excellent option for the prevention and/or treatment of both conditions. Here we report a series of relevantin vitroandin vivostudies on the bioactivity of an extract of mulberry leaves and its fractions obtained by a stepwise gradient on silica gel.In vivoantihyperglycemic and antihyperuricemic activity, plasma antioxidant status, as well asin vitroglucose consumption by adipocytes in the presence or absence of insulin, xanthine oxidase inhibition, free radical scavenging activity, and inhibition of lipid peroxidation were tested. Known bioactive constituents ofM. alba(chlorogenic acid, rutin, isoquercitrin, and loliolide) were identified and quantified from the HPLC-DAD fingerprint chromatograms. Iminosugar contents were investigated by MS/MS, 1-deoxynojirimycin was quantified, and amounts of 2-O-alpha-D-galactopyranosyl-1-deoxynojirimicin and fagomine were additionally estimated.

scholarly journals Free Radicals Scavenging Capacity, Antidiabetic and Antihypertensive Activities of Flavonoid-Rich Fractions from Leaves ofTrichilia emeticaandOpilia amentaceain an Animal Model of Type 2 Diabetes Mellitus

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Kiessoun Konaté ◽  
Kassi Yomalan ◽  
Oksana Sytar ◽  
Patrice Zerbo ◽  
Marian Brestic ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Animal Model ◽  
Type 2 Diabetes Mellitus ◽  
Therapeutic Potential ◽  
Radical Scavenging Activity ◽  
Radical Scavenging

Trichilia emeticaandOpilia amentaceatraditional Burkinabe medicinal plants were investigated to determine their therapeutic potential to inhibit key enzymes in carbohydrate metabolism, which has relevance to the management of type 2 diabetes.In vitroandin vivoantioxidant and antihypertensive potential and antilipidemia and antihyperglycemia activities in an animal model of type 2 diabetes mellitus have been studied. The antioxidant activity of the flavonoids from leaves ofTrichilia emeticaandOpilia amentaceahas been evaluated usingβ-carotene-linoleic acid system, 1,1-diphenyl-2-picrylhydrazyl inhibitory activity, chelation of iron (II) ions, and lipid peroxidation which showed more pronounced antioxidant capacities ofTrichilia emetica. Total cholesterol concentrations decreased in an animal model of type 2 diabetes mellitus under effects of flavonoid-rich fractions from leaves ofTrichilia emeticaandOpilia amentaceahas been observed. Extract of flavonoid-rich fractions fromTrichilia emeticashown maximum radical scavenging activity and possessed marked antiamylase activity which may be due to the presence of certain secondary metabolites. Suggested better antihyperglycemia, antilipidemia, and antihypertensive properties of flavonoid-rich fractions fromTrichilia emeticacompared to the extract ofOpilia amentaceaare demonstrating antidiabetic potential ofTrichilia emeticaas therapeutic targets for the management of type 2 diabetes.

scholarly journals Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 268
Author(s):  
Jonathan Ribot ◽  
Cyprien Denoeud ◽  
Guilhem Frescaline ◽  
Rebecca Landon ◽  
Hervé Petite ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Bone Marrow ◽  
Stromal Cells ◽  
Adipogenic Differentiation ◽  
Therapeutic Modality ◽  
Multipotent Stromal Cells ◽  
Cell Therapies

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

scholarly journals PAR-4/Ca2+-calpain pathway activation stimulates platelet-derived microparticles in hyperglycemic type 2 diabetes

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Alessandra Giannella ◽  
Giulio Ceolotto ◽  
Claudia Maria Radu ◽  
Arianna Cattelan ◽  
Elisabetta Iori ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Normal Glucose Tolerance ◽  
Calpain Inhibitor ◽  
Pathway Activation ◽  
Normal Glucose ◽  
Circulating Levels ◽  
Dependent Mechanism

Abstract Background Patients with type 2 diabetes (T2DM) have a prothrombotic state that needs to be fully clarified; microparticles (MPs) have emerged as mediators and markers of this condition. Thus, we investigate, in vivo, in T2DM either with good (HbA1c ≤ 7.0%; GGC) or poor (HbA1c > 7.0%; PGC) glycemic control, the circulating levels of MPs, and in vitro, the molecular pathways involved in the release of MPs from platelets (PMP) and tested their pro-inflammatory effects on THP-1 transformed macrophages. Methods In 59 T2DM, and 23 control subjects with normal glucose tolerance (NGT), circulating levels of CD62E+, CD62P+, CD142+, CD45+ MPs were determined by flow cytometry, while plasma levels of ICAM-1, VCAM-1, IL-6 by ELISA. In vitro, PMP release and activation of isolated platelets from GGC and PGC were investigated, along with their effect on IL-6 secretion in THP-1 transformed macrophages. Results We found that MPs CD62P+ (PMP) and CD142+ (tissue factor-bearing MP) were significantly higher in PGC T2DM than GGC T2DM and NGT. Among MPs, PMP were also correlated with HbA1c and IL-6. In vitro, we showed that acute thrombin exposure stimulated a significantly higher PMP release in PGC T2DM than GGC T2DM through a more robust activation of PAR-4 receptor than PAR-1 receptor. Treatment with PAR-4 agonist induced an increased release of PMP in PGC with a Ca2+-calpain dependent mechanism since this effect was blunted by calpain inhibitor. Finally, the uptake of PMP derived from PAR-4 treated PGC platelets into THP-1 transformed macrophages promoted a marked increase of IL-6 release compared to PMP derived from GGC through the activation of the NF-kB pathway. Conclusions These results identify PAR-4 as a mediator of platelet activation, microparticle release, and inflammation, in poorly controlled T2DM.

scholarly journals In Vitro Antioxidant and Anti-Diabetic Potential of Gymnema Sylvestre Methanol Leaf Extract

2017 ◽  
Vol 13 (36) ◽  
pp. 218 ◽  
Author(s):  
Ibrahim A. ◽  
Babandi A. ◽  
Tijjani A.A. ◽  
Murtala Y. ◽  
Yakasai H.M. ◽  
...  
Keyword(s):  
Normal Control ◽  
Leaf Extract ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Significant Inhibition ◽  
Alpha Amylase ◽  
Gymnema Sylvestre ◽  
Total Flavonoids Content

Some medicinal plants and their purified derivatives have demonstrated beneficial therapeutic potentials for many centuries. They have been reported to exhibit antioxidant activity, reducing the oxidative stress in cells and are therefore useful in the treatment of many human diseases, including diabetes and other non-communicable diseases. This study evaluated antioxidative activity and enzymatic (alpha-amylase and alphaglucosidase) inhibitory potentials of Gymnema sylvestre methanolic leaf extract (GSMLE) using standard methods. Phytochemical screening revealed the presence of alkaloids, tannins, saponins, steroids, terpenoids and flavonoids. The total phenolics and total flavonoids content in the extract were found to be 6.629±0.745 (µg/ml of catechol equivalent) and 0.004±0.0012 (µg/ml of quercetin equivalent) respectively. GSMLE was shown to have radical scavenging activity against DPPH (290.54 ± 39.72 %), hydroxyl radical (86.507 ± 23.55 %) and hydrogen peroxide (45.25 ± 25.23 %). The level of SOD was significantly decreased in H2O2 induced and H2O2+extract induced when compared with normal control (p<0.05); the level of GSH was significantly increased in H2O2 induced control and significantly decreased in H2O2+extract induced test when compared to normal control. GSH was also decreased significantly in H2O2+extract induced when compared to H2O2 induced control (p<0.05). The extract also demonstrated significant inhibition of alpha-glucosidase (IC50 182.26 ±1.05μg/ml) when compared with standard acarbose (IC50 189.52±0.46) and was more potent than the arcarbose on alpha-amylase inhibition with IC50 of 195.3±4.40 and 200.05±7.16 respectively. These findings may therefore, stress the potentiality of using Gymnema sylvestre as a natural remedy for the management of type 2 diabetes.

scholarly journals Study of Antimicrobial, Antioxidant and Cytotoxicity Properties of Selected Plant Extracts for Food Preservative Applications

2021 ◽  
pp. 95-111
Author(s):  
Tania Islam ◽  
Md Nazrul Islam ◽  
Wahidu Zzaman ◽  
Md Morsaline Billah
Keyword(s):  
Pathogenic Bacteria ◽  
Radical Scavenging Activity ◽  
Radical Scavenging ◽  
Antimicrobial Properties ◽  
In Vivo Studies ◽  
Diffusion Method ◽  
Plant Materials ◽  
Food Preservative

An attempt has been made to evaluate antimicrobial, antioxidant and cytotoxicity properties of extracts from onion (Allium cepa L.), garlic (Allium sativum), leaves of guava (Psidium guajava), papaya (Carica papaya), tea (Camellia sinensis), baen (Avicennia alba) and keora (Sonneratia apetala), respectively to apply as natural preservatives for tomatoes. The air-dried plant materials of the respective plant species were subjected to ethanol-methanol extraction, concentrated and stored at 4 °C before use. The extracts were dissolved in 95% ethanol for analysis of antioxidant and antimicrobial properties. Of the extracts tested, tea extracts showed the highest zone of inhibition against several pathogenic bacteria (E. coli 35.0±3.2 mm; P. aeruginosa 29.3±2.6 mm; S. typhi 28.4±2.1 mm and S. pyogenes 27.7±3.7 mm) using the disc diffusion method. In regard to DPPH free radical scavenging assay, keora and guava extracts showed the highest percentage of radical scavenging activity with the values of 89.64± 0.18 and 89.39± 0.88, respectively, which were in agreement with higher total antioxidant capacity (TAC) of these extracts obtained by the phosphomolybdenum method. Brine shrimp lethality bioassay for cytotoxicity assessment showed LC50 of 132.54 ± 18.99 µg/mL for the leaf extract of keora which was found to be most toxic among all studied extracts. The initial results indicated that the extracts could be used for food preservative applications based on the antimicrobial, antioxidant and cytotoxicity properties of the tested extracts. However, efficacy, stability and safety issues need to be addressed with both in vitro and in vivo studies.

Abstract 424: An IFNg-regulated Macrophage Protein Network Links Type 2 Diabetes to Atherosclerosis

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Catherine A Reardon ◽  
Amulya Lingaraju ◽  
Kelly Q Schoenfelt ◽  
Guolin Zhou ◽  
Ning-Chun Liu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Increased Risk ◽  
Macrophage Dysfunction ◽  
Macrophage Protein

Type 2 diabetics have a higher risk for atherosclerosis, but the mechanisms underlying the increased risk are poorly understood. Macrophages, which are activated in type 2 diabetes (T2D) and have a role in all stages of atherogenesis, are an attractive link. Our hypothesis is that T2D promotes macrophage dysfunction to promote atherosclerosis. To investigate the relationship between T2D and macrophage dysfunction, we used a proteomics approach to identify dysregulated proteins secreted from peritoneal macrophages in a diet induced mouse model of obesity and insulin resistance in the absence of hypercholesterolemia. Twenty-seven T2D responsive proteins were identified that predict defects in many of the critical functions of macrophages in atherosclerosis (e.g. decreased apoE- cholesterol efflux; decreased MFGE8 – efferocytosis, increased MMP12- matrix degradation). The macrophages from lean and obese mice were not lipid loaded, but the obese macrophages accumulated significantly more cholesterol when exposed to high levels of atherogenic lipoproteins in vitro suggesting that dysregulation of the T2D responsive proteins in diabetic mice render macrophages more susceptible to cholesterol loading. Importantly, many of these same protein changes, which were present in atherosclerotic Ldlr-/- mice with T2D, were normalized when these mice were fed non-diabetogenic hypercholesterolemic diets. Thus, foam cell formation in the presence and absence of T2D produces distinct effects on macrophage protein levels, and hence function. Further, we identify IFNγ as a mediator of the T2D responsive protein dysfunction. IFNγ, but not other cytokines, insulin or glucose, promote the T2D responsive protein dysregulation and increased susceptibility to cholesterol accumulation in vitro and the dysregulation is not observed in macrophage foam cells obtained from obese, diabetic IFNγ receptor 1 knockout animals. We also demonstrate that IFNγ can target these proteins in arterial wall macrophages in vivo . These studies suggest that IFNγ is an important mediator of macrophage dysfunction in T2D that may contribute to the enhanced cardiovascular risk in these patients.

Glucagon-like Peptide 1 Receptor Agonists, Diabetic Retinopathy and Angiogenesis: The AngioSafe Type 2 Diabetes Study

2019 ◽  
Vol 105 (4) ◽  
pp. e1549-e1560 ◽  
Author(s):  
Bénédicte Gaborit ◽  
Jean-Baptiste Julla ◽  
Samaher Besbes ◽  
Matthieu Proust ◽  
Clara Vincentelli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Fundus Photography ◽  
Endothelial Cell Proliferation ◽  
Receptor Agonists ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Aims Recent trials provide conflicting results on the association between glucagon-like peptide 1 receptor agonists (GLP-1RA) and diabetic retinopathy (DR). The aim of the AngioSafe type 2 diabetes (T2D) study was to determine the role of GLP-1RA in angiogenesis using clinical and preclinical models. Methods We performed two studies in humans. In study 1, we investigated the effect of GLP-1RA exposure from T2D diagnosis on the severity of DR, as diagnosed with retinal imaging (fundus photography). In study 2, a randomized 4-week trial, we assessed the effect of liraglutide on circulating hematopoietic progenitor cells (HPCs), and angio-miRNAs. We then studied the experimental effect of Exendin-4, on key steps of angiogenesis: in vitro on human endothelial cell proliferation, survival and three-dimensional vascular morphogenesis; and in vivo on ischemia-induced neovascularization of the retina in mice. Results In the cohort of 3154 T2D patients, 10% displayed severe DR. In multivariate analysis, sex, disease duration, glycated hemoglobin (HbA1c), micro- and macroangiopathy, insulin therapy and hypertension remained strongly associated with severe DR, while no association was found with GLP-1RA exposure (o 1.139 [0.800–1.622], P = .47). We further showed no effect of liraglutide on HPCs, and angio-miRNAs. In vitro, we demonstrated that exendin-4 had no effect on proliferation and survival of human endothelial cells, no effect on total length and number of capillaries. Finally, in vivo, we showed that exendin-4 did not exert any negative effect on retinal neovascularization. Conclusions The AngioSafe T2D studies provide experimental and clinical data confirming no effect of GLP-1RA on angiogenesis and no association between GLP-1 exposure and severe DR.

Animal Research for Type 2 Diabetes Mellitus, Its Limited Translation for Clinical Benefit, and the Way Forward

2018 ◽  
Vol 46 (1) ◽  
pp. 13-22 ◽  
Author(s):  
Zeeshan Ali ◽  
P. Charukeshi Chandrasekera ◽  
John J. Pippin
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Animal Models ◽  
Animal Research ◽  
Therapeutic Options ◽  
Research Findings

Obesity and type 2 diabetes mellitus (T2DM) have reached pandemic proportions worldwide, and considerable research efforts have been dedicated to investigating disease pathology and therapeutic options. The two hallmark features of T2DM, insulin resistance and pancreatic dysfunction, have been studied extensively by using various animal models. Despite the knowledge acquired from such models, particularly mechanistic discoveries that sometimes mimic human T2DM mechanisms or pathways, many details of human T2DM pathogenesis remain unknown, therapeutic options remain limited, and a cure has eluded research. Emerging human data have raised concern regarding inter-species differences at many levels (e.g. in gene regulation, pancreatic cytoarchitecture, glucose transport, and insulin secretion regulation), and the subsequent impact of these differences on the clinical translation of animal research findings. Therefore, it is important to recognise and address the translational gap between basic animal-based research and the clinical advances needed to prevent and treat T2DM. The purpose of this report is to identify some limitations of T2DM animal research, and to propose how greater human relevance and applicability of hypothesis-driven basic T2DM research could be achieved through the use of human-based data acquisition at various biological levels. This report addresses how in vitro, in vivo and in silico technologies could be used to investigate particular aspects of human glucose regulation. We do not propose that T2DM animal research has been without value in the identification of mechanisms, pathways, or potential targets for therapies, nor do we claim that human-based methods can provide all the answers. We recognise that the ultimate goal of T2DM animal research is to identify ways to advance the prevention, recognition and treatment of T2DM in humans, but postulate that this is where the use of animal models falls short, despite decades of effort. The best way to achieve this goal is by prioritising human-centred research.

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