scholarly journals Antidiabetic Potential of Prosopis farcta Roots: In Vitro Pancreatic Beta Cell Protection, Enhancement of Glucose Consumption, and Bioassay-Guided Fractionation

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Behzad Shahbazi ◽  
Saba Feyzmand ◽  
Fataneh Jafari ◽  
Nastaran Ghiasvand ◽  
Gholamreza Bahrami ◽  
...  

By using the streptozotocin- (STZ-) induced cytotoxicity in β-TC3 cells as an assay model, a bioassay-guided fractionation study was employed to isolate and characterize the potential antidiabetic principles of roots of Prosopis farcta. A combination of open column chromatography on reverse-phase silica gel using a water-ethanol gradient (10 : 90 to 100 : 0) followed by HPLC-based fractionation led to an active compound that appears to be composed of carbohydrate/sugar. When cell viability under STZ was reduced to 49.8 ± 4% (mean ± SD), treatment with the active compound at the concentration of 0.5 mg/mL either as a coadministration or a pretreatment improved the viability to 93 ± 1.9% and 91.5 ± 7%, respectively. The reduction in the mitochondrial membrane potential by STZ (47.34 ± 8.9% of control) was similarly recovered to 84.5 ± 4.3 (coadministration) and 88 ± 5.5% (pretreatment) by the active fraction. The bioassay-guided fractionation, β-cell protective effect, and increased glucose consumption (up to 1.49-fold increase) in hepatocytes by the extracts and active fraction are also discussed.

2015 ◽  
Vol 51 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Azar Hosseini ◽  
Reza Shafiee-Nick ◽  
Ahmad Ghorbani

Although currently available drugs are useful in controlling early onset complications of diabetes, serious late onset complications appear in a large number of patients. Considering the physiopathology of diabetes, preventing beta cell degeneration and stimulating the endogenous regeneration of islets will be essential approaches for the treatment of insulin-dependent diabetes mellitus. The current review focused on phytochemicals, the antidiabetic effect of which has been proved by pancreatic beta cell protection/regeneration. Among the hundreds of plants that have been investigated for diabetes, a small fraction has shown the regenerative property and was described in this paper. Processes of pancreatic beta cell degeneration and regeneration were described. Also, the proposed mechanisms for the protective/regenerative effects of such phytochemicals and their potential side effects were discussed.


2013 ◽  
Vol 8 (5) ◽  
pp. 1934578X1300800
Author(s):  
Guy E. Raoelison ◽  
Mamy H. Rafamantanana ◽  
René Razafindrazaka ◽  
Adolphe Randriantsoa ◽  
Suzanne Urverg-Ratsimamanga ◽  
...  

Spirospermum penduliflorum Thouars (Menispermaceae) is widely used on the eastern coast of Madagascar to treat hypertension. The aim of the present study was to analyse the vasorelaxant properties of different leaf extracts. The activity of the n-hexane, dichloromethane and methanolic extracts was tested on phenylephrine-contracted aorta. The dichloromethane extract was shown to be the most effective. Further fractionation of this extract led to the isolation of an active fraction relaxing phenylephrine-contracted aorta with an IC50 of 0.18 μg/mL {log IC50 (μg/mL) −0.74 ± 0.03} but was much less effective on KCl induced contractions. Bioassay-guided fractionation of this fraction led to the isolation of two aporphinoid alkaloids, neolitsine and dicentrine, which at concentrations of 0.1 μM and 1 μM displaced to the right the phenylephrine concentration-contraction curve. Our results show that Spirospermum penduliflorum extracts possess vasorelaxant activity in vitro that could be related to the presence of dicentrine in the extracts having an α1 antagonist activity. This finding is not in accord with the previous studies by Rasoanaivo et al where no alkaloids were detected in the leaves of Spirospermum penduliflorum.


1976 ◽  
Vol 35 (02) ◽  
pp. 350-357 ◽  
Author(s):  
Hana Bessler ◽  
Galila Agam ◽  
Meir Djaldetti

SummaryA three-fold increase of protein synthesis by human platelets during in vitro phagocytosis of polystyrene latex particles was detected. During the first two hours of incubation, the percentage of phagocytizing platelets and the number of latex particles per platelet increased; by the end of the third hour, the first parameter remained stable, while the number of latex particles per cell had decreased.Vincristine (20 μg/ml of cell suspension) inhibited platelet protein synthesis. This effect was both time- and dose-dependent. The drug also caused a decrease in the number of phagocytizing cells, as well as in their phagocytotic activity.


1994 ◽  
Vol 72 (05) ◽  
pp. 685-692 ◽  
Author(s):  
Michael T Nurmohamed ◽  
René J Berckmans ◽  
Willy M Morriën-Salomons ◽  
Fenny Berends ◽  
Daan W Hommes ◽  
...  

SummaryBackground. Recombinant hirudin (RH) is a new anticoagulant for prophylaxis and treatment of venous and arterial thrombosis. To which extent the activated partial thromboplastin time (APTT) is suitable for monitoring of RH has not been properly evaluated. Recently, a capillary whole blood device was developed for bed-side monitoring of the APTT and it was demonstrated that this device was suitable to monitor heparin therapy. However, monitoring of RH was not evaluated.Study Objectives. To evaluate in vitro and ex vivo the responsiveness and reproducibility for hirudin monitoring of the whole blood monitor and of plasma APTT assays, which were performed with several reagents and two conventional coagulometers.Results. Large interindividual differences in hirudin responsiveness were noted in both the in vitro and the ex vivo experiments. The relationship between the APTT, expressed as clotting time or ratio of initial and prolonged APTT, and the hirudin concentration was nonlinear. A 1.5-fold increase of the clotting times was obtained at 150-200 ng/ml plasma. However, only a 2-fold increase was obtained at hirudin levels varying from 300 ng to more than 750 ng RH/ml plasma regardless of the assays. The relationship linearized upon logarithmic conversion of the ratio and the hirudin concentration. Disregarding the interindividual differences, and presuming full linearity of the relationship, all combinations were equally responsive to hirudin.Conclusions. All assays were equally responsive to hirudin. Levels up to 300 ng/ml plasma can be reliably estimated with each assay. The manual device may be preferable in situations where rapid availability of test results is necessary.


1966 ◽  
Vol 51 (2) ◽  
pp. 193-202
Author(s):  
J. A. Antonioli ◽  
A. Vannotti

ABSTRACT 1. The metabolism of suspensions of circulating leucocytes has been studied after intramuscular injection of a dose of 50 mg/kg of a corticosteroid (cortisone acetate). The suspensions were incubated under aerobic conditions in the presence of a glucose concentration of 5.6 mm. Glucose consumption, lactate production, and variations in intracellular glycogen concentration were measured. After the administration of the corticosteroid, the anabolic processes of granulocyte metabolism were reversibly stimulated. Glucose consumption and lactate production increased 12 hours after the injection, but tended to normalize after 24 hours. The glycogen content of the granulocytes was enhanced, and glycogen synthesis during the course of the incubation was greatly stimulated. The action of the administered corticosteroid is more prolonged in females than in males. The injection of the corticosteroid caused metabolic modifications which resemble in their modulations and in their chronological development those found in circulating granulocytes of guinea-pigs suffering from sterile peritonitis. These results suggest, therefore, that, in the case of acute inflammation, the glucocorticosteroids may play an important role in the regulation of the metabolism of the blood leucocytes.


2007 ◽  
Vol 30 (4) ◽  
pp. 96
Author(s):  
Michael R. Ward ◽  
Qiuwang Zhang ◽  
Duncan J. Stewart ◽  
Michael J.B. Kutryk

Autologous endothelial progenitor cells (EPCs) have been used extensively in the development of cell-based therapy for acute MI. However, EPCs isolated from patients with CAD and/or CAD risk factors have reduced regenerative activity compared to cells from healthy subjects. As in endothelial cells, endothelial NO synthase (eNOS) expression and subsequent NO production are believed to be critical determinants of EPC function. Recently, the ability of EPCs to migrate in vitro in response to chemotactic stimuli has been shown to predict their regenerative capacity in clinical studies. Therefore, we hypothesized that the regenerative function of EPCs from patients with or at high risk for CAD will be enhanced by overexpression of eNOS, as assessed by migratory capacity. Methods: EPCs were isolated from the blood of human subjects with CAD risk factors (>15% Framingham risk score; FRS) (± CAD) by Ficoll gradient separation and differential culture. Following 3 days in culture, cells were transduced using lentivirus vectors containing either eNOS or GFP (sham) at an MOI of 3. The cells were cultured for an additional 5 days before being used in functional assays. Cell migration and chemotaxis in response to VEGF (50 ng/mL) and SDF-1 (100 ng/mL) were assessed using a modified Boyden Chamber assay. Results: Transduction at an MOI of 3 led to a ~90-100-fold increase in eNOS mRNA expression and a 5-6 fold increase in eNOS protein expression, as assessed by qRT-PCR and Western Blotting. Moreover, there was a significant improvement in the migration of EPCs following eNOS transduction compared to sham-transduced EPCs in response to both VEGF (44.3 ± 8.4 vs. 31.1 ± 4.6 cells/high power field; n=10, p < 0.05) and SDF-1 (51.9 ± 11.1 vs. 34.5 ± 3.3 cells/HPF; n=10, p < 0.05). Conclusions: These data show that the reduced migration capacity of EPCs isolated from patients with CAD and/or CAD risk factors can be significantly improved through eNOS overexpression in these cells. Thus, eNOS transduction of autologous EPCs may enhance their ability to restore myocardial perfusion and function following acute MI. We intend to further explore the regenerative potential of eNOS-transduced EPCs using various in vitro and in vivo models.


2020 ◽  
Vol 21 (5) ◽  
pp. 438-450
Author(s):  
Ramya Ramchandran ◽  
Swetha Ramesh ◽  
Anviksha A ◽  
RamLal Thakur ◽  
Arunaloke Chakrabarti ◽  
...  

Background:: Antifungal cyclic lipopeptides, bioactive metabolites produced by many species of the genus Bacillus, are promising alternatives to synthetic fungicides and antibiotics for the biocontrol of human pathogenic fungi. In a previous study, the co- production of five antifungal lipopeptides homologues (designated as AF1, AF2, AF3, AF4 and AF5) by the producer strain Bacillus subtilis RLID 12.1 using unoptimized medium was reported; though the two homologues AF3 and AF5 differed by 14 Da and in fatty acid chain length were found effective in antifungal action, the production/ yield rate of these two lipopeptides determined by High-Performance Liquid Chromatography was less in the unoptimized media. Methods:: In this study, the production/yield enhancement of the two compounds AF3 and AF5 was specifically targeted. Following the statistical optimization (Plackett-Burman and Box-Behnken designs) of media formulation, temperature and growth conditions, the production of AF3 and AF5 was improved by about 25.8- and 7.4-folds, respectively under static conditions. Results:: To boost the production of these two homologous lipopeptides in the optimized media, heat-inactivated Candida albicans cells were used as a supplement resulting in 34- and 14-fold increase of AF3 and AF5, respectively. Four clinical Candida auris isolates had AF3 and AF5 MICs (100 % inhibition) ranging between 4 and 16 μg/ml indicating the lipopeptide’s clinical potential. To determine the in vitro pharmacodynamic potential of AF3 and AF5, time-kill assays were conducted which showed that AF3 (at 4X and 8X concentrations) at 48h exhibited mean log reductions of 2.31 and 3.14 CFU/ml of C. albicans SC 5314, respectively whereas AF5 at 8X concentration showed a mean log reduction of 2.14 CFU/ml. Conclusion:: With the increasing threat of multidrug-resistant yeasts and fungi, these antifungal lipopeptides produced by optimized method promise to aid in the development of novel antifungal that targets disease-causing fungi with improved efficacy.


2019 ◽  
Vol 16 (5) ◽  
pp. 478-491 ◽  
Author(s):  
Faizan Abul Qais ◽  
Mohd Sajjad Ahmad Khan ◽  
Iqbal Ahmad ◽  
Abdullah Safar Althubiani

Aims: The aim of this review is to survey the recent progress made in developing the nanoparticles as antifungal agents especially the nano-based formulations being exploited for the management of Candida infections. Discussion: In the last few decades, there has been many-fold increase in fungal infections including candidiasis due to the increased number of immunocompromised patients worldwide. The efficacy of available antifungal drugs is limited due to its associated toxicity and drug resistance in clinical strains. The recent advancements in nanobiotechnology have opened a new hope for the development of novel formulations with enhanced therapeutic efficacy, improved drug delivery and low toxicity. Conclusion: Metal nanoparticles have shown to possess promising in vitro antifungal activities and could be effectively used for enhanced and targeted delivery of conventionally used drugs. The synergistic interaction between nanoparticles and various antifungal agents have also been reported with enhanced antifungal activity.


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