A double-blinded, randomized, placebo-controlled study evaluating the impact of dates vinegar consumption on blood biochemical and hematological parameters in patients with type 2 diabetes

Purpose: To determine the effects of dates vinegar on blood biochemical and hematological parameters in type 2 diabetic subjects.Methods: Current research focused on fifty-five subjects having blood sugar more than126 mg/dL. Participants ingested dates vinegar (20 mL) daily into their normal diets for a period of 10 weeks. Glycated hemoglobin (HbA1c), fasting blood sugar (FBS), total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine (Cr), urea, complete blood count (CBC), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), potassium and folate levels were analyzed before, after 5 weeks and after the experiment Results: Dates vinegar improved the blood concentrations of HbA1c (6.80 ±2.34 to 6.17 ± 2.14 (%)), FBS (171.43 ±36.74 to 147.56 ± 38.86 mg/dL,p=0.001), TC (218.10 ± 16.9 to 191.14 ± 14.23 mg/dL, p<0.001), ALT (24.94 ± 5.03 to 21.88±5.08 IU/L, p=0.002) and ALP (264.32± 45.26 to 257.30 ±44.21 IU/L) and folate (34.6 ± 6.6 to 41.7 ± 6.5 nmol/ L, p<0.001).Conclusion: Dates vinegar significantly improved the total cholesterol.The other blood biochemical and hematological factors were also improved however; the improvements were not significant.Keywords: Dates vinegar, diabetes, glycated hemoglobin, hyperlipidemi

Hybrid Quinoline-Thiosemicarbazone Therapeutics as a New Treatment Opportunity for Alzheimer’s Disease‒Synthesis, In Vitro Cholinesterase Inhibitory Potential and Computational Modeling Analysis

From MDPI via Jisc Publications RouterHistory: accepted 2021-10-27, pub-electronic 2021-10-30Publication status: PublishedAlzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. The limited pharmacological approaches based on cholinesterase inhibitors only provide symptomatic relief to AD patients. Moreover, the adverse side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with these drugs and numerous clinical trial failures present substantial limitations on the use of medications and call for a detailed insight of disease heterogeneity and development of preventive and multifactorial therapeutic strategies on urgent basis. In this context, we herein report a series of quinoline-thiosemicarbazone hybrid therapeutics as selective and potent inhibitors of cholinesterases. A facile multistep synthetic approach was utilized to generate target structures bearing multiple sites for chemical modifications and establishing drug-receptor interactions. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). In vitro inhibitory results revealed compound 5b as a promising and lead inhibitor with an IC50 value of 0.12 ± 0.02 μM, a 5-fold higher potency than standard drug (galantamine; IC50 = 0.62 ± 0.01 μM). The synergistic effect of electron-rich (methoxy) group and ethylmorpholine moiety in quinoline-thiosemicarbazone conjugates contributes significantly in improving the inhibition level. Molecular docking analysis revealed various vital interactions of potent compounds with amino acid residues and reinforced the in vitro results. Kinetics experiments revealed the competitive mode of inhibition while ADME properties favored the translation of identified inhibitors into safe and promising drug candidates for pre-clinical testing. Collectively, inhibitory activity data and results from key physicochemical properties merit further research to ensure the design and development of safe and high-quality drug candidates for Alzheimer’s disease

Impact of vitamin C supplementation on composition, stability, fatty acids profile, organic acids, antioxidant properties and sensoric acceptability of cultured buttermilk

Buttermilk is a fermented drink widely used all over the world. It is produced widely both traditionally and commercially through pasteurization. Buttermilk, produced during churning of cultured cream, was supplemented with vitamin C at four different concentrations i.e., 100, 200, 300, 400 mg/100 ml, and zero concentrations (T1, T2, T3, T4 and control) and was evaluated for different parameters. Vitamin C supplementation at all concentrations had no effect on compositional attributes of buttermilk (p>0.05). The results also showed that concentration of vitamin C supplemented buttermilk in T1, T2, T3, T4, and control was 98.81, 196.14, 277.38, 382.19, and 0 mg/100 ml (p0.05) respectively. Oleic acid content in control, T1, T2, T3, T4 was 35.79, 35.75, 35.65, 35.63 and 35.19% (p>0.05). Linoleic acid content in control, T1, T2, T3, and T4 was 7.49, 7.05, 7.13, 7.10 and 7.33% (p0.05) but the variation is due to storage period. Total antioxidant capacity of T1, T2, T3, T4 and control was 35.72, 42.74, 52.93, 68.77 and 84.66% (p0.05). According to trained judges, sensory evaluation of all the treatments were performed on a 9 point hedonic scale and the results showed a non-significant difference between control and treatments. From commercial point of view, sensory results were promising as vitamin C did not affect sensory attributes of buttermilk which is quite acceptable from consumer perspective. It is therefore concluded from the results that buttermilk can be supplemented with vitamin C

Preliminary study to evaluate the phytochemicals and physiochemical properties in red and black date's vinegar

Antioxidant activity, total phenolic content (TPC), total flavonoids, carotenoids, pH, and total titratable acidity of red and black date's vinegar were analyzed. The extraction method was designed and optimized for this purpose with respect to the variety and solvent concentrations along with the time of ultrasonication. The results showed that red dates' vinegar has significantly (p < 0.05) higher total phenols (3.38 ± 0.13 mg GAE/ml) and antioxidant activity as compared to black dates' vinegar, which had a higher amount of carotenoids (3.43 ± 0.11 mg/100 ml). Similarly, red dates' vinegar has more flavonoids as compared to commercially available Zhenjiang vinegar. In terms of physiochemical properties, both red and black date's vinegar were not significantly different (p > 0.05). Use of 50% and 80% methanol with 25 min of ultrasonication for extraction seemed more effective. The total phenols, flavonoids, antioxidant activity, carotenoids, and physiochemical analysis of the red and black date's vinegar indicated that vinegar from dates (red or black dates) is a competitive product in the marketplace

Hybrid Quinoline-Thiosemicarbazone Therapeutics as a New Treatment Opportunity for Alzheimer’s Disease‒Synthesis, In Vitro Cholinesterase Inhibitory Potential and Computational Modeling Analysis

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the leading cause of dementia worldwide. The limited pharmacological approaches based on cholinesterase inhibitors only provide symptomatic relief to AD patients. Moreover, the adverse side effects such as nausea, vomiting, loss of appetite, muscle cramps, and headaches associated with these drugs and numerous clinical trial failures present substantial limitations on the use of medications and call for a detailed insight of disease heterogeneity and development of preventive and multifactorial therapeutic strategies on urgent basis. In this context, we herein report a series of quinoline-thiosemicarbazone hybrid therapeutics as selective and potent inhibitors of cholinesterases. A facile multistep synthetic approach was utilized to generate target structures bearing multiple sites for chemical modifications and establishing drug-receptor interactions. The structures of all the synthesized compounds were fully established using readily available spectroscopic techniques (FTIR, 1H- and 13C-NMR). In vitro inhibitory results revealed compound 5b as a promising and lead inhibitor with an IC50 value of 0.12 ± 0.02 μM, a 5-fold higher potency than standard drug (galantamine; IC50 = 0.62 ± 0.01 μM). The synergistic effect of electron-rich (methoxy) group and ethylmorpholine moiety in quinoline-thiosemicarbazone conjugates contributes significantly in improving the inhibition level. Molecular docking analysis revealed various vital interactions of potent compounds with amino acid residues and reinforced the in vitro results. Kinetics experiments revealed the competitive mode of inhibition while ADME properties favored the translation of identified inhibitors into safe and promising drug candidates for pre-clinical testing. Collectively, inhibitory activity data and results from key physicochemical properties merit further research to ensure the design and development of safe and high-quality drug candidates for Alzheimer’s disease

Design and synthesis of novel anti-urease imidazothiazole derivatives with promising antibacterial activity against Helicobacter pylori.

Urease enzyme is a known therapeutic drug target for treatment of Helicobacter pylori infection due to its role in settlement and growth in gastric mucosa. In this study, we designed a new series of sulfonates and sulfamates bearing imidazo[2,1-b]thiazole scaffold that exhibit a potent inhibitory activity of urease enzyme. The most potent compound 2c inhibited urease with an IC50 value of 2.94 ± 0.05 μM, which is 8-fold more potent than the thiourea positive control (IC50 = 22.3 ± 0.031 μM). Enzyme kinetics study showed that compound 2c is a competitive inhibitor of urease. Molecular modeling studies of the most potent inhibitors in the urease active site suggested multiple binding interactions with different amino acid residues. Phenotypic screening of the developed compounds against H. pylori delivered molecules of that possess high potency (1a, 1d, 1h, 2d, and 2f) in comparison to the positive control, acetohydroxamic acid. Additional studies to investigate the selectivity of these compounds against AGS gastric cell line and E. coli were performed. Permeability of the most promising derivatives (1a, 1d, 1h, 2d, and 2f) in Caco-2 cell line, was investigated. As a result, compound 1d presented itself as a lead drug candidate since it exhibited a promising inhibition against urease with an IC50 of 3.09 ± 0.07 μM, MIC value against H. pylori of 0.031 ± 0.011 mM, and SI against AGS of 6.05. Interestingly, compound 1d did not show activity against urease-negative E. coli and exhibited a low permeability in Caco-2 cells which supports the potential use of this compound for GIT infection without systemic effect