Pronounced Hypoglycemic Effect Research Articles

Evaluation and comparison of efficacy and safety of tirzepatide, liraglutide and SGLT2i in patients with type 2 diabetes mellitus: a network meta-analysis.

The objective is to assess the effectiveness and safety of tirzepatide, liraglutide, and SGLT2i in individuals diagnosed with type 2 diabetes. An inquiry was undertaken within the electronic database spanning from its inception to February 11th, 2024, aimed at identifying randomized controlled trials that assess the efficacy and safety of tirzepatide, liraglutide, canagliflozin, ertugliflozin, empagliflozin, dapagliflozin, and henagliflozin. Perform a network meta-analysis to examine the distinctions among them (PROSPERO registration number: CRD42024537006). Twenty-eightRCTs were included, involving 8499 participants. Compared with placebo, all treatments improved HbA1c levels: tirzepatide 15 mg reduced HbA1c the most (MD [95% CI], -2.24% [-2.52, -1.96]%), followed by tirzepatide 10 mg (MD [95% CI], -1.99% [-2.29, -1.69]%), tirzepatide 5 mg (MD [95% CI], -1.82% [-2.11, -1.53]%), and liraglutide 1.2 mg (MD [95% CI], -1.23% [-1.41, -1.05]%). Canagliflozin 300 mg also showed a significant reduction in HbA1c (MD [95% CI], -1.00% [-1.18, -0.82]). Tirzepatide was also the most effective in promoting weight loss, with the following results compared with placebo: tirzepatide 15 mg (MD [95% CI], -8.74 kg [-9.83, -7.66] kg), tirzepatide 10 mg (MD [95% CI], -7.13 kg [-8.40, -5.88] kg), tirzepatide 5 mg (MD [95% CI], -5.38 kg [-6.65, -4.11] kg), canagliflozin 300 mg (MD [95% CI], -2.31 kg [-2.79, -1.83] kg), and empagliflozin 10 mg (MD [95% CI], -2.00 kg [-2.44, -1.55] kg). In reducing systolic blood pressure (SBP), canagliflozin 300 mg showed the greatest effect (MD [95% CI], -5.96% [-7.96, -3.96] %). For diastolic blood pressure (DBP), henagliflozin 5 mg demonstrated the most significant reduction compared to placebo (MD [95% CI], -2.46% [-3.82, -1.10] %). Liraglutide 1.8 mg was most likely to cause adverse events (AE) (OR [95% CI], 2.57 [1.78, 3.70]), but there was no significant difference in serious adverse events (SAEs) between the interventions (including placebo). Out of the seven medications examined in this study, tirzepatide demonstrates the most effective antidiabetic and weight-reducing effects. Furthermore, the dosage of Liraglutide at 1.2 mg and above demonstrates a more pronounced hypoglycemic effect in comparison to SGLT2 inhibitors. SGLT2 inhibitors exhibit a distinct hypotensive effect and are suitable for diabetic individuals experiencing hypertension.

Research on the effects of intestinal FXR agonists and antibiotics on the regulation of red kidney bean polysaccharides in the liver metabolism in mice with type 2 diabetes

AbstractOur previous study revealed that red kidney bean polysaccharides (RKB) exhibit a pronounced hypoglycemic effect on type 2 diabetic rats, while simultaneously exerting a significant ameliorative impact on hepatic damage in these animals. However, the precise mechanism underlying the effects of RKB on diabetes and liver metabolism remains unproven. In this study, we utilized a mouse model of type 2 diabetes induced by a high‐fat diet combined with streptozotocin to investigate the impact of RKB. We administered a combined intervention involving antibiotics, fexaramine, and RKB to elucidate the mechanism underlying RKB's effects. Our findings demonstrated that RKB significantly ameliorated liver function indices and histopathological injuries. Nevertheless, when antibiotics and fexaramine were introduced as interventions, they hindered the beneficial effects of RKB on liver function in type 2 diabetic mice. Furthermore, our nontargeted metabolomics analysis revealed that antibiotics and fexaramine exerted their inhibitory actions on RKB efficacy through modulation of distinct metabolites involved in glycerophospholipid and purine metabolic pathways.

The Active Ingredient Catalpol in Rehmannia glutinosa Reduces Blood Glucose in Diabetic Rats via the AMPK Pathway.

Type 2 diabetes mellitus (T2DM) poses a huge threat to population health globally, and more drugs need to be explored for treatment. In this study, we investigated the mechanism of active ingredient catalpol in Rehmannia glutinosa on reduces blood glucose in diabetic. The T2DM model was constructed by intraperitoneal injection of streptozotocin into Sprague-Dawley (SD) rats, which were randomly grouped into diabetes model group, pioglitazone group, Rehmannia glutinosa group, catalpol high-dose group, catalpol low-dose group and normal control group.The intervention was continued for 28 d, and changes in body weight, fasting blood glucose, insulin and lipid levels were observed. Of all the drugs, pioglitazone had the most pronounced hypoglycemic effect, which began to decline after 2 weeks of treatment in the low-dose catalpol group and had no hypoglycemic effect in the high-dose catalpol group. Among them, Rehmannia glutinosa was able to increase serum triglyceride level, and pioglitazone effectively reduced total cholesterol level in rats. The low dose of catalpol decreased the concentration of low-density lipoprotein cholesterol (LDL), while the high dose of catalpol increased the concentration of LDL. As an active ingredient in Rehmannia glutinosa, catalpol has the potential to lower blood glucose and improve blood lipids in diabetes treatment, and its action may be achieved by regulating the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway, which provides a new idea for the development of new diabetes therapeutic approaches.

Neuroprotective potential of gliflozins

Gliflozins are a relatively new class of oral antihyperglycemic drugs that are increasingly being introduced into routine practice in the treatment of patients with type 2 diabetes mellitus (DM2). The hypoglycemic effect of gliflozins is associated with the stimulation of glucosuria, however, in addition to a pronounced hypoglycemic effect and high safety, these drugs also have many pleiotropic properties, due to the presence of many direct and indirect points of application. The purpose of this paper is to provide an overview of the currently best studied neuroprotective effects of this class of drugs. As materials in the course of the work, studies of foreign colleagues published in the period 2008–2022 were used. Analysis of the works showed that the neuroprotective effect of gliflozins is associated with many different mechanisms. Thus, gliflozins realize an anti-inflammatory effect by activating the M2 subpopulation of macrophages, reducing pro-inflammatory neurotransmitters (related primarily to the inflammasome). In addition, by reducing the activity of the mTOR signaling pathway, the drugs reduce the amount of beta-amyloid and improve neurotransmission. A group of works also showed the antiacetylcholinesterase effect of gliflozins, not to mention the decrease in the intensity of non-enzymatic protein glycation and insulin resistance. All of the above mechanisms provide an anti-inflammatory, anti-atherogenic effect, improve cognitive abilities in patients, reduce the frequency of hemorrhagic stroke, and can also potentially improve prognosis in patients with Alzheimer’s disease (AD). The effects described above were obtained during preclinical trials and many experimental studies, and some effects have already demonstrated their consistency in prospective clinical trials. However, the data obtained are still insufficient to form clear indications for this class of drugs in neurology, so the topic requires further study and clinical trials.

Neuroprotective potential of incretinomimetics

In the prescriptions of an endocrinologist to patients with diabetes mellitus, glucagon-like peptide agonists, belonging to the group that affects the incretin system of the body, have recently been increasingly appearing. In addition to the pronounced hypoglycemic effect and high safety, these drugs also have many pleiotropic properties due to the presence of glucagon-like peptide receptors in the vascular endothelium, kidneys, heart and nervous tissue. The purpose of this work is to describe the most studied neuroprotective effects of this class of drugs. As materials in the course of the work, studies of domestic and foreign colleagues published in the period from 2008 to 2022 were used. Our work has shown that the neuroprotective effect of GLP-1 is associated with the activation of the corresponding receptor systems in the central nervous system, which leads to increased cellular survival in ischemic conditions by reducing reactive oxygen species, stimulating beta-oxidation by mitochondria, and reducing pro-inflammatory cytokines. In addition, the analysis of the literature also established the positive role of GLP-1 in neurodegenerative diseases – drugs reduce the amount of unnormal proteins (alphasynuclein, microtubular T-peptide, etc.), reduce the activity of non-enzymatic glycation of proteins in hyperglycemia, as well as reduce insulin resistance. The effects described above were analyzed during preclinical trials of GLP-1, and also demonstrated their validity in human models during some clinical trials. However, the data obtained is not yet sufficient to form clear indications for this class of drugs in neurology, so the topic requires further study and large clinical trials.

Synthesis and Evaluation of Hypoglycemic Activity of Structural Isomers of ((Benzyloxy)phenyl)propanoic Acid Bearing an Aminobornyl Moiety.

Free fatty acid receptor-1 (FFAR1) agonists are promising candidates for therapy of type 2 diabetes because of their ability to normalize blood sugar levels during hyperglycemia without the risk of hypoglycemia. Previously, we synthesized compound QS-528, a FFA1 receptor agonist with a hypoglycemic effect in C57BL/6NCrl mice. In the present work, structural analogs of QS-528 based on (hydroxyphenyl)propanoic acid bearing a bornyl fragment in its structure were synthesized. The seven novel compounds synthesized were structural isomers of compound QS-528, varying the positions of the substituents in the aromatic fragments as well as the configuration of the asymmetric center in the bornyl moiety. The studied compounds were shown to have the ability to activate FFAR1 at a concentration of 10 μM. The cytotoxicity of the compounds as well as their effect on glucose uptake in HepG2 cells were studied. The synthesized compounds were found to increase glucose uptake by cells and have no cytotoxic effect. Two compounds, based on the meta-substituted phenylpropanoic acid, 3-(3-(4-(((1R,2R,4R)-1,7,7-trimethylbicyclo-[2.2.1]heptan-2-ylamino)methyl)benzyloxy)phenyl)propanoic acid and 3-(3-(3-(((1R,2R,4R)-1,7,7-trimethylbicyclo [2.2.1]heptan-2-ylamino)methyl)benzyloxy)phenyl)propanoic acid, were shown to have a pronounced hypoglycemic effect in the oral glucose tolerance test with CD-1 mice.

Study of hypoglycemic properties of «Glyphasonorm» tablets and «Glyphasolin» capsules on the streptozotocin-induced diabetic rat model

The risk of developing any complications of diabetes is significantly reduced by monitoring and correcting blood glucose levels and blood pressure, as well as by observing healthy lifestyle rules. Early detection and treatment of type 2 diabetes contribute to the prevention of disease progression and the development of complications.
 The aim is to study the hypoglycemic effect of «Glyphasonorm» tablets and «Glyphasolin» capsules in a rat model of streptozotocin-induced diabetes.
 Materials and methods. The studies were carried out on Wistar rats injected intraperitoneally with nicotinamide at a dose of 230 mg/kg 15 minutes before intravenous injection of streptozotocin at a dose of 65 mg/kg. The dynamics of body weight of rats, glucose and glycosylated haemoglobin levels under the impact of long-term administration of metformin, «Glyphasonorm» tablets and «Glyphasolin» capsules were investigated.
 Results and discussion. The studies on a streptozotocin-induced diabetic model have established that under the action of «Glyphasonorm» tablets and «Glyphasolin» capsules, the level of glycosylated haemoglobin, which decreased along with the level of glucose in the blood of animals, was significantly reduced in comparison with diabetic control. After 14 days of research, the "Glyphasolin" capsules showed more pronounced hypoglycemic activity (4.4 % and 8.0 % more) than the "Glyphasonorm" tablets and the reference drug metformin. The «Glyphasolin» capsules on the 12th day of the study showed a marked decrease in glycosylated haemoglobin in the blood of animals (3.1 % and 5.6 % more) than the «Glyphasonorm» tablets and metformin.
 Conclusions. In the experimental model of streptozotocin diabetes in rats, "Gliphasolin" capsules showed a more pronounced hypoglycemic effect, which was manifested by a decrease in the content of glycosylated haemoglobin in the blood and prevailed over the effect of the comparative drug metformin and "Gliphasonorm" tablets.
 «Glyphasolin» capsules and «Glyphasonorm» tablets based on bioflavonoid complex from bean show promise in the treatment of type 2 diabetes on the background of obesity and reducing the risk of micro- and macroangiopathy

9-N-n-alkyl Berberine Derivatives: Hypoglycemic Activity Evaluation

Several novel 9-N-n-alkyl derivatives of berberine (C5, C7, C10, C12) were synthesized. They were analyzed in vitro and in vivo for their hypoglycemic activity. In vitro studies showed that the derivatives with shorter alkyl substitutes at concentrations ranging from 2.5 to 10 μM were able to stimulate glucose consumption by HepG2 cells more prominently than the derivatives with longer substitutes (C10 and C12). All compounds demonstrated a better effect compared to berberine. Their impact on cells' viability also depended on the alkyl substitutes length, but in this case, C10 and C12 derivatives demonstrated the best results. A similar correlation was also found in the OGTT, where the C5 derivative demonstrated a pronounced hypoglycemic effect at a dose of 15 mg/kg and C12 was less effective. This compound was further investigated in C57BL/6Ay mice for four weeks and was administered at a dose of 15 mg/kg. Pronounced effect of C12 on carbohydrate metabolism in mice was discovered: there was a decrease in fasting glucose levels and an increase in glucose tolerance in OGTT on the 14th and 28th days of the experiment. However, at the end of the experiment, signs of hepatosis exacerbation and an increase in the content of hepatic aminotransferases in blood were found.

Synthesis and Pharmacological Evaluation of (+)-Usnic Acid Derivatives as Hypoglycemic Agents

Usnic acid is produced by lichens and exhibits different biological properties, including hypoglycemic ones. However, this effect becomes noticeable only at relatively high doses, something that may lead to some adverse effects. The chemical modification of the molecule is able to enhance its safety profile and its hypoglycemic properties. We synthesized six enamine derivatives of (+)-usnic acid, and two of them are novel. All compounds were evaluated for the hypoglycemic effect after oral introduction in mice with alloxan-induced diabetes mellitus at a dose of 50 mg/kg. The derivative containing a 4-trifluoromethylphenyl fragment showed the most pronounced hypoglycemic effect, which was detected starting from sixth day of the experiment. Also, OGTT was performed in mice without alteration of glucose metabolism (C57BL/6), which showed no hypoglycemic effect after oral introduction of all studied compounds.

Assessment of the influence of the mineral complex of rutin on the degree of expression of anti-diabetic activity

Assessment of the influence of the mineral complex of rutin on the degree of expression of anti-diabetic activity

Medicinal Plants Galega officinalis L. and Yacon Leaves as Potential Sources of Antidiabetic Drugs.

Hypoglycemic and antioxidant properties of extracts of medicinal plants Galega officinalis L. (aboveground part) and yacon (Smallanthus sonchifolius Poepp. & Endl.) (leaves) as potential sources of biologically active substances with antidiabetic action have been studied. The pronounced hypoglycemic effect of Galega officinalis extract, devoid of alkaloids, at a dose of 600 mg/kg in experimental diabetes mellitus (DM) has been proven. The established effect is evidenced by a decrease in the concentration of glucose and glycosylated hemoglobin in the blood, increase glucose tolerance of cells, increase C-peptide and insulin content in the plasma of rats’ blood. The effective hypoglycemic effect of the extract in the studied pathology was confirmed by histological examination of the pancreas. The cytoprotective effect of the studied extract on pancreatic cells at a dose of 1200 mg/kg was experimentally confirmed. In the standard cut area, an increase was found in the number of Langerhans islets, their average area, diameter, volume, and a number of β-cells relative to these indicators in animals with diabetes. Comparative screening of the antioxidant properties of 30, 50, 70, and 96% water–ethanol extracts of yacon indicates the highest potential of 50% water-ethanol extract to block free radicals in in vitro model experiments. The non-alkaloid fraction of Galega officinalis extract showed moderate antioxidant activity and was inferior to yacon extract in its ability to neutralize reactive oxygen species (ROS) and bind metal ions of variable valence. The level of antioxidant potential of the studied extracts is due to differences in the quantitative content of compounds of phenolic nature in their compositions. The obtained data on the biological effects of Galega officinalis extract on the structural and functional state of β-cells of the pancreas and antioxidant properties of Galega officinalis and yacon extracts substantiate the prospects of using these plants to create antidiabetic medicines and functional foods based on them.

Вплив речовин гумінової природи на вуглеводний обмін при алоксан-індукованому цукровому діабеті у щурів

The article presents study results of the effect of humic nature biologically active additive «Humilid» on carbohydrate metabolism, namely on glucose, insulin and C-peptide in alloxan-induced diabetes mellitus in rats. The purpose of the experiment was to investigate how “Humilid” affects carbohydrate metabolism in rats; to study and analyze the effect of the humic nature biologically active substance «Humilid» on metabolic processes. In the work we used biochemical methods for studying the blood of experimental rats. Adult male white rats were taken for the experiment, from which four groups were formed. The experiment lasted three weeks, during which the animals from the first experimental group received daily in addition to the main feed an aqueous solution of feed additive «Humilid» at dose 5 mg / kg of body weight of the active substance, and had free access to water. Rats of the second and third groups were injected with alloxan as a single intraperitoneal injection. The rats of the third group additionally received an aqueous solution of feed additive «Humilid». It was identified that “Humilid” has an antioxidant activity, which may be one of the mechanisms of its antidiabetic action, as it is known that alloxan causes free radical damage to β-cells with weak antioxidant protection. The use of a biologically active feed additive of humic nature was found to have a hypoglycemic effect in both healthy animals as well as in rats with alloxan-induced diabetes mellitus. It was found that the use of “Humilid” in rats enhances energy processes in their bodies of experimental animals. There was a decrease in glucose content in rats from second group by 11.9% (P ≤ 0.001) compared with the control one. At the same time, the glucose content in animals from third and fourth groups was higher by 35.9% (P ≤ 0.001) and 20% (P ≤ 0.001) higher than in animals from the control one. The insulin concentration in the blood of rats from the second group was 7.4% higher (P ≤ 0.05) compared to the animals from first group. The concentration of C-peptide was within the reference values. The levels of insulin and C-peptide concentration in animals of the third and groups were lower by 47.8% (P ≤ 0.001) and 32.4% (P ≤ 0.001) and 55.5% (P ≤ 0.001) and 37.5% (P ≤ 0.001) in comparison with animals of first group. A pronounced hypoglycemic effect, which was due to an increase in the sensitivity of tissues to glucoregulatory hormones and an increase in the body’s tolerance to excessive intake of carbohydrates. The obtained results of the study indicate the regulatory effect of humic feed additive «Humilid» on key links in the regulation of carbohydrate metabolism, which is characterized by the decrease in blood glucose level due to activation of the synthesis and secretion of insulin and C-peptide.

HYPOGLYCEMIC ACTIVITY OF NANOCHROMIUM CITRATE

The study deals with clarification of nanochromium citrate (NCC) effect on glucose level in the blood of animals in a wide range of doses under various regimens (single, repeated) and ways of administration. Objective: to investigate nanochromium citrate effect on glucose level in the blood of normoglycemic animals under various conditions and regimens of administration. Material and methods. The study was conducted on 84 mature male rats with the body weight of 160-180 g. During screening examination glucose concentration in the blood of intact (normoglycemic) rats was determined after NCC single administration through the peritoneum in a wide range of doses (0,22; 0,11; 0,04; 0,02; 0,01 mg/kg), different more than 20 times and were 5; 2,5; 1; 0,5; 0,25% from DL50 respectively. Blood was taken for analysis 2 hours after NCC administration. In other series hypoglycemic activity of NCC was examined after a long (14 days) administration into the peritoneum and intracutaneously. Glucose level in the blood taken from the caudal vein was determined by means of glucometer (Accu-Chek Active New, Germany). Results. After a single NCC administration into the peritoneum in the doses 0,22; 0,11 mg/kg (5; 2,5% from DL50) hypoglycemic effect was not observed, with smaller doses – 0,04; 0,02 mg/kg (1%; 0,5% from DL50) it was unreliable, and with NCC in the still smaller dose – 0,01 mg/kg (0,25% from DL50) glucose concentration in the blood decreased 17.6% (p<0,05) in comparison with the control animals. Thus, from a wide range of the examined doses the most pronounced hypoglycemic effect of NCC was found to occur in the dose of 0,01 mg/kg, which can be considered as conditionally effective. Against a background of repeated (14 days) administrations of NCC in the doses of 0,01 and 0,02 mg/kg glucose level in the blood 47,3% and 44,6% decreased respectively in comparison with the control animals. The bigger the dose of NCC (0,04; 0,11; 0,22 mg/ kg) was, the smaller glucose concentration became, less pronounced – 39,1%, 39,1%; 38,85%; and 36,7%. That is, together with a course dose increase hypoglycemic activity of NCC decreases similar to that of a single administration. Comparison of sugar reducing effect of NCC in intact animals under conditions of a single and long (14 days) administration into the peritoneum in similar doses indicated that hypoglycemic effect of NCC was more pronounced during repeated administrations (on an average 1,5 times, р<0,01). Similar to a single administration an inversely proportional dependence is seen between a sugar reducing effect and the dose given: with smaller doses (0,01 mg/kg) hypoglycemic effect of NCC was more pronounced than with bigger ones and vice-versa. After a long (14 days) administration into the stomach sugar reducing effect of NCC remains and increases analogically to administration into the peritoneum with longer introduction. On the one hand, the obtained results of hypoglycemic activity of NCC with a long administration in different ways (intracutaneously, intraperitoneally) are indicative of the lack of tolerance with repeated NCC administration. On the other hand, hypoglycemic activity is intensified with a reduced dose. Conclusions. 1. NCC demonstrates hypoglycemic action during parenteral (into the peritoneum) and enteral (intracutaneous) administrations and depends on the dose and regimens of use. The most pronounced hypoglycemic effect of NCC is found after a single administration in the dose of 0,01 mg/kg (0,25% from DL50) as conditionally effective. 2. During a long (14 days) administration into the peritoneum and intracutaneously hypoglycemic activity of NCC remains and increases. An inversely proportional dependence is observed between hypoglycemic effect of NCC and the dose given.

Physiological and biochemical studies as a necessary component of the algorithm for assessing the effectiveness of food minor biologically active substances

Preclinical physiological and biochemical studies of the effectiveness of the tested biologically active substances in the conditions of simulated pathology in laboratory animals are an important stage preceding the assessment of the clinical effectiveness of the created specialized foods for therapeutic or preventive nutrition. The aim of this work is a brief review of the developed algorithm for preclinical assessment of the effectiveness of specialized foods, which includes a set of sequential stages of testing the safety, stability, bioavailability and effectiveness of biologically active substances in experiments on laboratory animals. Results. The paper presents a brief review of methodological approaches for in vivo preclinical assessment of the effectiveness of minor plant biologically active substances - polyphenols from bilberry fruits and leaves and phytoecdysteroids extracted from spinach. A beneficial effect of bilberry leaves' polyphenols on carbohydrate and lipid metabolism of male Zucker and Wistar rats was shown, which determined the necessity to increase the effectiveness of the developed polyphenolic ingredient by sorption on a food carrier. When evaluating the in vivo effects of polyphenols from blueberries and leaves sorbed on buckwheat flour, a pronounced hypoglycemic effect was found. The experiments aimed to the assessment of the adaptogenic effects of phytoecdysteroids from spinach leaves showed a significant decrease in the content of the main biomarkers of the stress system, which indicates a «smoothing» of the response of the animal organism to a strong stress impact. Conclusion. The inclusion of minor biologically active substances into the composition of foods for preventive and therapeutic nutrition is the necessary condition to improve their effectiveness. The scientific and practical significance of the preclinical evaluation to a decisive extent depends on the presence of a correctly selected biomodel. Thus, the adequacy of the assessment of the effects of minor biologically active substances as functional food ingredients in the composition of the specialized food products depends on the reproducibility of pathological processes (clinical, biochemical and morphological disorders) characteristic for the studied disease on the selected in vivo model.

Insulin-loaded mucoadhesive nanoparticles based on mucin-chitosan complexes for oral delivery and diabetes treatment

In this study, insulin-loaded nanoparticles (NPs) were prepared via self-gelation method using chitosan and aqueous soluble snail mucin as natural polymers. Herein, mucins were ionically interacted with chitosan at different concentrations to obtained insulin-loaded NPs, labelled as A1 (1:1) (i.e., chitosan 2 % w/v + mucin 2 % w/v) and A2 (2:1) (chitosan 4 % w/v + mucin 2 % w/v), using poloxamer and poly vinyl alcohol as solid surfactant. Such formulation was selected to provide the necessary dynamics for the formation of the nanoparticles while maintaining the surface properties that will favor the encapsulation of insulin. Each system was characterized in terms of their particle size distribution, morphology, zeta potential, and polydispersity index. In vitro release of insulin was evaluated in acidic solution (pH 1.2) and phosphate buffer solution (pH 7.4), and the hypoglycaemic activity was evaluated in diabetes rats. The prepared insulin-loaded NPs displayed particles with relatively smooth surfaces and an average particle size of 479.6 and 504.1 nm for A1 and A2, respectively. Zeta potential and polydispersity index, ranged from 22.1 to 31.2 mV and 0.155–0.185, respectively. The encapsulating efficiency for the systems A1 and A2 were 88.6 and 92.5, respectively, and a self-sustained release of encapsulated insulin was observed for over a period of 8 h. In vivo studies revealed a pronounced hypoglycaemic effect in diabetic rats after peroral administration of the insulin-loaded NPs compared to the effect caused by free oral insulin solution. In addition, both the pharmacokinetic and toxicity results showed low plasma clearance of insulin and no signs of toxicity on the liver enzyme and cell viability, which suggested good biocompatibility of the NPs formulations. Overall, the formation of NPs of insulin with chitosan and snail mucin represents a potentially safe and promising approach to protect insulin and enhance its peroral delivery.

The study of antidiabetic action of the phlomis pungens extract

Topicality . Despite the rather large arsenal of antidiabetic drugs, the main goal of DM pharmacotherapy, aimed at reducing hyperglycemia and progress of diabetic vascular complications, still remains far from practical implementation. In this regard, the expansion of antidiabetic drugs spectrum due to natural biologically active substances is actual and promising. Aim. To study the antidiabetic action of phlomis pungens extract. Materials and methods. Trials were performed on 33 rats. Experimental diabetes was caused by a single intravenous alloxan injection at a dose of 70 mg/kg to females weighing 200-250 g. The extract of the Phlomis Pungens (PP) was injected once a day intragastrically at doses of 25 and 50 mg/kg daily for three weeks prior to modeling of experimental diabetes, and for 30 days of the experiment. Control animals received water in a similar regime. Metformin was used as a reference preparation in a dose of 100 mg/kg. Intraperitoneal glucose tolerance test was performed as follows: after night fasting (16-18 hours) rats intraperitoneally injected glucose solution at a dose of 3 g/kg in the morning. Results and discussion. Experimental diabetes was caused by a single intravenous alloxan injection at a dose of 70 mg/kg to females weighing 200-250 g. Basal glycemia was determined in dynamics: baseline level and after alloxan injection - at the 3rd (period of acute development of hyperglycemia), 1, 2 and 4 weeks of the trial. As a result of the trial it was established that the extract of the Phlomis Pungens (PPE) demonstrates a hypoglycemic effect in a dose of25 m 50 mg/kg for 4 weeks of the trial. The most pronounced hypoglycemic effect of PPE demonstrated by the end of the trial, i.e. at 4 weeks and significantly reduced the blood glucose level in comparison with the control pathology (CP) by 40 %. According to hypoglycemic activity, the extract of Phlomis Pungens in 2 doses of 25 and 50 mg/kg demonstrated almost the same effect and did not differ significantly between each other. Conclusions. The Phlomis Pungens Extract demonstrated a pronounced hypoglycemic effect against the background of exudate alloxan diabetes of moderate severity. Against the backdrop of a glucose load, the Phlomis Pungens extract reduces the level of basal glycemia by decreasing insulin resistance and exceeds the activity of metformin at a dose of 50 mg/kg.

Gynura divaricata rich in 3, 5\u2212/4, 5-dicaffeoylquinic acid and chlorogenic acid reduces islet cell apoptosis and improves pancreatic function in type 2 diabetic mice

BackgroundDiabetes mellitus is one of the most common chronic diseases that accompanied by severe complications. Gynura divaricata (GD), a medicinal and edible plant that is usually used for the treatment of diabetes. Therefore, this study investigates the chemical components of GD with hypoglycemic effect and the possible mechanism lowering blood sugar in T2D diabetic mice.MethodsThe methanol extract of GD was analysed by HPLC-DAD. And then mice with type 2 diabetes induced by a high-fat diet in combination with streptozotocin feed the diet containing lyophilized GD powder for 4 weeks. During this period, fasting blood glucose (FBG) levels and body weight were measured.ResultsGD was rich in four bioactive components of dicaffeoylquinic acid and chlorogenic acid. These components occupied about 2.37% in the GD powder in which the highest level was 3, 5-dicaffeoylquinic acid. Oral GD significantly reduced FBG, fasting serum insulin, and glycosylated serum protein levels, and enhanced antioxidative activities. HE-staining showed that the pathological damage in pancreatic β-cells was ameliorated. An immunohistochemical assay also showed that GD promoted marked pancreatic β-cell regeneration. GD also caused notable increase in GLUT2, GK, MafA, PDX-1, and Bcl-2 as well as reduction in Bax and caspase-3 expression as shown by western blot analysis.ConclusionsGD exerts the pronounced hypoglycaemic effect by inhibiting islet cell apoptosis and improving pancreatic function. Therefore, GD might have a potential to improve diabetes.

Preparation, characterization and in vivo evaluation of pH sensitive, safe quercetin-succinylated chitosan-alginate core-shell-corona nanoparticle for diabetes treatment

The study aims for development of an efficient polymeric carrier for evaluating pharmaceutical potentialities in modulating the drug profile of quercetin (QUE) in anti-diabetic research. Alginate and succinyl chitosan are focused in this investigation for encapsulating quercetin into core-shell nanoparticles through ionic cross linking. The FT-IR, XRD, NMR, SEM, TEM, drug entrapment and loading efficiency are commenced to examine the efficacy of the prepared nanoparticles in successful quercetin delivery. Obtained results showed the minimum particle size of ∼91.58nm and ∼95% quercetin encapsulation efficiently of the particles with significant pH sensitivity. Kinetics of drug release suggested self-sustained QUE release following the non-fickian trend. A pronounced hypoglycaemic effect and efficient maintenance of glucose homeostasis was evident in diabetic rat after peroral delivery of these quercetin nanoparticles in comparison to free oral quercetin. This suggests the fabrication of an efficient carrier of oral quercetin for diabetes treatment.

Unraveling the active hypoglycemic agent trigonelline in Balanites aegyptiaca date fruit using metabolite fingerprinting by NMR

Trigonelline (3-carboxy-1-methyl pyridinium) was identified as a relevant bioactivity and taste imparting component in Balanites aegyptiaca fruit, using 1H NMR of crude extracts without any fractionation or isolation step. The structural integrity of trigonelline was established within the extract matrix via1H NMR, 1H–1H COSY, HMQC and HMBC and by comparison with authentic standard. A quantitative 1H NMR method (qHNMR) was used to determine trigonelline concentrations in the peel and pulp of B. aegyptiaca fruit of 8 and 13mgg−1, respectively. Trigonelline so far has not been reported from B. aegyptiaca or its genus as it easily escapes LC–MS based detection. Its discovery provides novel insight into the balanite fruits antidiabetic properties as the compound is known for a pronounced hypoglycemic effect. In addition, it is likely to impart the perceptible bitter taste portion to balanites sweet bitter taste. UPLC–MS of the crude extract additionally revealed the fruit flavonoid pattern showing quercetin/isorhamnetin flavonol conjugates in addition to epicatechin, the latter being present at much lower levels.

Anti-diabetic effect mediated by Ramulus mori polysaccharides

Diabetes mellitus is a complicated metabolic disease, whose pathogenesis is related to apoptosis within pancreatic tissue. In this study, the potential therapeutic benefits of Ramulus mori polysaccharides (RMP) on streptozotocin (STZ)-induced diabetic mice were evaluated. Our experiments indicated that RMP lowered hyperglycemia and increased insulin levels in diabetic mice. Histopathological examination revealed that RMP contributed to the reduction of STZ-lesioned pancreatic cells. In addition, the serum level of HbA1c was decreased. RMP treatment also showed increased Bcl-2 expression and reduced Bax protein level in pancreatic tissue. Furthermore, intrapancreatic expressions of p-JNK, p-p38 and cleaved-caspase-3 were down-regulated by RMP treatment. Collectively, the findings demonstrate that RMP exerts the pronounced hypoglycemic effect via regulation of the intrapancreatic JNK/p38 pathway to protect against STZ-induced apoptosis in pancreatic tissue, eventually ameliorating metabolic function in the pancreas.