A possible alternative therapy for type 2 diabetes using Myristica fragrans Houtt in combination with glimepiride: in vivo evaluation and in silico support

2020 ◽  
Vol 75 (3-4) ◽  
pp. 103-112
Author(s):  
Waheeda Nasreen ◽  
Suchitra Sarker ◽  
Md. Abu Sufian ◽  
F.A. Dain Md. Opo ◽  
Mohammad Shahriar ◽  
...  

AbstractThe current study aimed to evaluate the in vivo hypoglycemic potential of Myristica fragrans seed extract co-administered with glimepiride in Swiss albino mice. Computational tools were used to further verify the in vivo findings and to help compare this combination to the glimepiride-pioglitazone combination in terms of the binding affinity of the ligands to their respective target protein receptors and the relative stability of the drug-protein complexes. The effect of the combined therapy was observed both in alloxan- and glucose-induced hyperglycemic Swiss albino mice. The mean fasting blood glucose level of the test groups was measured and statistically evaluated using Student’s t test. The combined therapy significantly reduced the blood glucose level in a time-dependent manner compared to glimepiride alone. The binding affinity of glimepiride was found to be −7.6 kcal/mol with sulfonylurea receptor 1 in molecular docking. Conversely, macelignan-peroxisome proliferator-activated receptor (PPAR) α and macelignan-PPAR γ complexes were stabilized with −9.2 and −8.3 kcal/mol, respectively. Molecular dynamic simulation revealed that macelignan-PPAR α and γ complexes were more stable than pioglitazone complexes. The combination shows promise in animal and computer models and requires further trials to provide evidence of its activity in humans.

2021 ◽  
Vol 4 (1) ◽  
pp. 1-6
Author(s):  
Usman Garkuwa ◽  
Buhari Ibrahim ◽  
Aisha Balanmalam ◽  
Sayyadatu Muhammad ◽  
Mustapha Muazu ◽  
...  

Curcuma longa (C. longa), also known as curcumin, is a lipophilic polyphenol substance proven to have cholesterol-lowering, anti-diabetic, anti-inflammatory, anti-oxidant, and anti-cancer properties in both in vitro and in vivo models. Most previous studies investigated the effect of C. longa on diabetic mice and therefore, there is a need to investigate the effect of C. longa on normoglycemic mice. Depression is a common consequence of anxiety that affects 21% of the world’s population. Since the prevalence of diabetes and depression is on the rise globally, it is important to search for safer and cost-effective management for these disorders. In doing so, it is therefore essential to investigate its effect in normoglycemic mice. The current study determines the effect of C. longa on blood glucose level and anxiety-like behavior in normoglycemic Swiss albino mice. A total of 20 mice were divided into four groups of five (n=5 per group). Group I (control) received distilled water 10 ml/kg, groups II, III, and IV received C. longa at 5%, 10%, and 20%, respectively, for 14 days. We found that 20% C. longa group showed a significant (p<0.05) increase in fasting blood glucose level (195.84±14.46 mg/dl) after 14 days of administration compared with the control group (134.60±4.52 mg/dl).  We also found that 20% C. longa increased the anxiety-like behavior in normoglycemic Swiss albino mice compared with the control group. However, there was no significant (p>0.05) difference in both fasting blood glucose level and anxiety-like behavior between the mice treated with 5% and 10% C. longa and the control group. This study indicates that C. longa at high concentration is unsafe for consumption by normoglycemic Swiss albino mice.


Author(s):  
Adel M. Aly ◽  
Ahmed S. Ali

: Glipizide (GZ) is an oral blood-glucose-lowering drug of the sulfonylurea class characterized by its poor aqueous solubility. Aiming for the production of GZ tablets with rapid onset of action followed by prolonged effect; GZ-Polyethylene glycol (PEG 4000 and 6000) solid dispersions with different ratios, (using melting and solvent evaporation method), as well as, coprecipitate containing GZ with polymethyl-methacrylate (PMMA) were prepared. Four tablet formulations were prepared containing; a) GZ alone, b) GZ: PEG6000, 1:10, c) GZ:PMMA 1:3, and, d)both GZ:PEG6000 1:10 and GZ:PMMA 1:3. The solvent evaporation method showed more enhancement of GZ solubility than the melting one, and this solubilizing effect increased with PEG increment. Generally, PEG6000 showed more enhancement of dissolution than PEG4000 especially at 1:10 drug: polymer ratio (the most enhancing formula). Also, the prepared tablet formulations showed acceptable physical properties according to USP/NF requirements. The dissolution results revealed that tablets containing PEG6000 (1:10) have the most rapid release rate, followed by the formula containing both PEG6000 and PMMA, while that including PMMA alone showed the slowest dissolution rate. Moreover, In-vivo studies for each of the above four formulations, were performed using four mice groups. The most effective formula in decreasing the blood glucose level, through the first 6 hours, was that containing GZ and PEG6000, 1:10. However, formula containing the combination of enhanced and sustained GZ was the most effective in decreasing the blood glucose level through 16 hours. Successful in-vitro in-vivo correlations could be detected between the percent released and the percent decreasing of blood glucose level after 0.5 hours.


2019 ◽  
Vol 9 (3) ◽  
pp. 248-263 ◽  
Author(s):  
Ashish K. Parashar ◽  
Preeti Patel ◽  
Arun K. Gupta ◽  
Neetesh K. Jain ◽  
Balak Das Kurmi

Background: The present study was aimed at developing and exploring the use of PEGylated Poly (propyleneimine) dendrimers for the delivery of an anti-diabetic drug, insulin. Methods: For this study, 4.0G PPI dendrimer was synthesized by successive Michael addition and exhaustive amidation reactions, using ethylenediamine as the core and acrylonitrile as the propagating agent. Two different activated PEG moieties were employed for PEGylation of PPI dendrimers. Various physicochemical and physiological parameters UV, IR, NMR, TEM, DSC, drug entrapment, drug release, hemolytic toxicity and blood glucose level studies of both PEGylated and non- PEGylated dendritic systems were determined and compared. Results: PEGylation of PPI dendrimers caused increased solubilization of insulin in the dendritic framework as well as in PEG layers, reduced drug release and hemolytic toxicity as well as increased therapeutic efficacy with reduced side effects of insulin. These systems were found to be suitable for sustained delivery of insulin by in vitro and blood glucose-level studies in albino rats, without producing any significant hematological disturbances. Conclusion: Thus, surface modification of PPI dendrimers with PEG molecules has been found to be a suitable approach to utilize it as a safe and effective nano-carrier for drug delivery.


1997 ◽  
Vol 87 (2) ◽  
pp. 354-360 ◽  
Author(s):  
Yumiko Ishizawa ◽  
Shuichiro Ohta ◽  
Hiroyuki Shimonaka ◽  
Shuji Dohi

Background Although hyper- and hypoglycemia induce neurophysiologic changes, there have been no reports on the effects of blood glucose changes on anesthetic requirements. This study examined the effects of hyper- and hypoglycemia on the minimum alveolar concentration (MAC) of halothane in rats. In addition, based on a previous finding that the level of brain acetylcholine was reduced during mild hypoglycemia, the authors examined the influence of physostigmine on MAC during hypoglycemia. Methods In Sprague-Dawley rats, anesthesia was induced and maintained with halothane in oxygen and air. The MAC was determined by observing the response to tail clamping and tested during mild hypoglycemia (blood glucose level, 60 mg/dl) and hyperglycemia (blood glucose level, 300 and 500 mg/dl) induced by insulin and glucose infusion, respectively (experiment 1). The effects of 0.3 and 1.0 mg/kg physostigmine given intraperitoneally on MAC were examined in rats with mild and severe hypoglycemia (blood glucose level, 60 and 30 mg/dl; experiment 2). Results In experiment 1, mild hypoglycemia significantly reduced the MAC of halothane (0.76 +/- 0.03%) compared with the control value (0.92 +/- 0.04%), but hyperglycemia did not change MAC. In experiment 2, mild and severe hypoglycemia reduced MAC of halothane in a degree-dependent manner. Physostigmine (1 mg/kg) had no effect on MAC regardless of blood glucose level, but 0.3 mg/kg reduced MAC. Conclusions Hypoglycemia reduced anesthetic requirements in a degree-dependent manner, whereas hyperglycemia had no effects. Although the mechanism of hypoglycemic MAC reduction needs further investigations, physostigmine studies suggest that this may not be related to inhibition of cholinergic transmission.


Author(s):  
Shibu Narayan Jana ◽  
Papiya Mitra Mazumder

Objective: The present study was aimed at the development of partial pancreatectomy in a murine model for diabetes.Methods: Diabetes model was successfully developed by partial pancreatectomy method. In this study, cyclosporine was used for influenced the glycaemic status. Diabetes status was evaluated by fasting blood glucose level (FBG), lipid profile (by estimation of total cholesterol level and HDL-level), serum amylase and biochemical assay like glutathione estimation.Results: We report here the restoration of euglycaemic status in cyclosporine-induced diabetic in swiss albino mice after 30% pancreatectomy. In this study, Pancreatectomised (partial) group of animals showed a rapid elevation of glycaemic status, starting from 15th post observational d, but the level of significance decreased gradually from 15th (P<0.01) to 60th (P<0.05) d. This was probably due to nesidioblastotic activity which shifted the fasting blood glucose level towards normoglycaemic status with β-cells regeneration. Cyclosporine treated a group of mice showed normoglycaemic status throughout the whole experimental period, but the cholesterol level remained significant (P<0.001) till the end of the experimental d. Gradually decrements in glycaemia of the diabetic pancreatectomised animals demonstrate islets neogenesis occurring after the operative activity, leading to normoglycaemic condition, probably attributed to β-cells proliferation.Conclusion: The biochemical and histopathological evaluations suggest that there is the development of the diabetic model in the pancreatectomized group and diabetes status induced by pancreatectomy is curable to a certain extent due to the regeneration of β-cells.


2020 ◽  
Vol 23 (2) ◽  
pp. 135-140
Author(s):  
Md Monirul Islam ◽  
Tufael Ahmed ◽  
Hajera Khatun ◽  
Mohammad A Rashid

The fruits of Stixis suaveolens (Roxb.) have been a popular folk medicine among traditional practitioners. However, there are questions about its traditional uses due to lack of scientific evidence. This study was aimed to evaluate the effects of crude methanol extract of fruits of S. suaveolens in mice model. The central and peripheral analgesic activity were evaluated using the ‘tail flick’ and ‘writhing’ assay respectively. The anti-hyperglycemic potential was assessed by the ability of the crude extract in reducing blood glucose level in mice after oral administration of glucose. Oral administration (400 mg/kg bw) of the extract showed significant (p<0.001) delay in pain sensation and inhibition of acetic acid induced writhing response in mice model. The results were compared with the respective standard morphine (2 mg/kg bw) and diclofenac (50 mg/kg bw). Likewise, in anti-hyperglycemic assay, maximum reduction (p<0.001) of blood glucose level (39.6%) was observed 120 min after oral intake (400 mg/kg bw) of the extract as compared that exhibited by the standard drug, glibenclamide (46.83%). The in vivo bioassays confirmed that the crude methanolic extract of fruits of S. suaveolens possesses significant central- and peripheral-analgesic as well as anti-hyperglycemic activities. These findings justify its popularity as a traditional medicine and hence demands future study involving isolation and characterization of its bioactive compounds. Bangladesh Pharmaceutical Journal 23(2): 135-140, 2020


Author(s):  
Sachiko Kessoku ◽  
Katsuhiko Maruo ◽  
Shinpei Okawa ◽  
Kazuto Masamoto ◽  
Yukio Yamada

Various non-invasive glucose monitoring methods using near-infrared spectroscopy have been investigated although no method has been successful so far. Our previous study has proposed a new promising method utilizing numerically generated absorbance spectra instead of the experimentally acquired absorbance spectra. The method suggests that the correct estimation of the optical properties is very important for numerically generating the absorbance spectra. The purpose of this study is to measure the change in the optical properties of the skin with the change in the blood glucose level in vivo. By measuring the reflectances of light incident on the skin surface at two distances from the incident point, the optical properties of the skin can be estimated. The estimation is a kind of the inverse problem based on the simulation of light propagation in the skin. Phantom experiments have verified the method and in vivo experiments are to be performed.


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