Hyperglycemic Rats Research Articles

Isolation and characterization of anti-diabetic compound from Clerodendrum infortunatum L. leaves

Clerodendrum infortunatum L. (CI) leaves are traditionally used in the treatment of diabetic patients. This study aimed to isolate and characterize bioactive compounds from CI leaves and evaluate their anti-diabetic activities (ADI). The CI leaves extracts ADI was estimated on streptozotocin-induced hyperglycemic rats by applying a different dose of extract and compared with the anti-diabetic medicine (Glibenclamide). The intraperitoneal's acute effect showed the progressive fall of the blood glucose level until 120 min on diabetic rats by applying the CI extract. Continuous administration of the target ethanolic extracts of CI at 0 to 28 days leads to a decrease in fasting serum glucose (FSG), total cholesterol (TG), and low-density lipoprotein (LDL) levels, while high-density lipoprotein (HDL) was increased. The ethanolic extract of CI produced five fractions, fraction-1 indicated a greater insulin secretion effect compared to other fractions. So, the structure of fraction-1 was elucidated and characterized by IR, 1H, 13C-NMR, COSY, and MS and the identified compound name is phaeophytin a. This study suggests that phaeophytin a exhibits significant anti-diabetic activity.

Protective Effect of Raf-1 Kinase Inhibitory Protein on Diabetic Retinal Neurodegeneration through P38-MAPK Pathway

ABSTRACT Purpose This study aimed to investigate the effect of Raf-1 kinase inhibitory protein (RKIP) on diabetic retinal neurodegeneration in streptozotocin-treated rat model and high glucose-treated rat Müller cells. Methods Control and streptozotocin-treated rats were intravitreally injected with saline, RKIP gene overexpression lentivirus (oeRKIP) or negative control lentivirus (RKIP-vector). Normal or high glucose-treated Müller cells were transfected with saline, RKIP gene overexpression lentivirus or negative control lentivirus. Western blotting and immunofluorescence assay were utilized to evaluate the function of RKIP on the expression of RKIP, p38 mitogen-activated protein kinase (p38-MAPK), glutamate/aspartate transporter (GLAST), glutamine synthetase (GS), glial fibrillar acidic protein (GFAP) and cysteine-aspartic acid protease-3 (caspase-3). A glutamate assay kit was adopted to detect glutamate level in retina samples. Apoptosis of Müller cells was determined by Annexin-V/PI staining and flow cytometry. Results High glucose-treated Müller cells exhibited promoted apoptosis, while RKIP overexpression in high glucose-treated Müller cells down-regulated the enhanced apoptosis. Compared with rats injected with saline, streptozotocin-treated hyperglycemic rats displayed enhancement in the immunoreactivities of p38-MAPK and GFAP as well as in the protein expression of p38-MAPK and caspase-3. Strikingly, intravitreal injection of RKIP gene overexpression lentivirus in the hyperglycemic rats reversed the augmented immunoreactivities and protein expression mentioned above. Meanwhile, RKIP overexpression in the hyperglycemic rats improved the immunoreactivities and protein expression of RKIP, GS and GLAST. Besides, RKIP down-regulated the increased level of retinal glutamate in the hyperglycemic rats. Conclusions Intravitreal injection of RKIP gene overexpression lentivirus functioned in preventing diabetic retinal neurodegeneration in a rat model of diabetes presumably by inhibiting p38-MAPK pathway.

Selenium attenuates ischemia/reperfusion injury‑induced damage to the blood‑brain barrier in hyperglycemia through PI3K/AKT/mTOR pathway‑mediated autophagy inhibition.

Ischemic stroke is a leading cause of mortality and disability. Diabetes mellitus, characterized by hyperglycemia, is a common concomitant disease of ischemic stroke, which is associated with autophagy dysfunction and blood-brain barrier (BBB) damage following cerebral ischemia/reperfusion (I/R) injury. At present, there is no effective treatment strategy for the disease. The purpose of the present study was to explore the molecular mechanisms underlying the protective effects of selenium on the BBB following I/R injury in hyperglycemic rats. Middle cerebral artery occlusion was performed in diabetic Sprague-Dawley rats. Treatment with selenium and the autophagy inhibitor 3-methyladenine significantly reduced cerebral infarct volume, brain water content and Evans blue leakage, while increasing the expression of tight junction (TJ) proteins and decreasing that of autophagy-related proteins (P<0.05). In addition, selenium increased the phosphorylation levels of PI3K, AKT and mTOR (P<0.05). A mouse bEnd.3 brain microvascular endothelial cell line was co-cultured in vitro with an MA-h mouse astrocyte-hippocampal cell line to simulate the BBB. The cells were then subjected to hyperglycemia, followed by oxygen-glucose deprivation for 1 h and reoxygenation for 24 h. It was revealed that selenium increased TJ protein levels, reduced BBB permeability, decreased autophagy levels and enhanced the expression of phosphorylated (p)-AKT/AKT and p-mTOR/mTOR proteins (P<0.05). Treatment with wortmannin (an inhibitor of PI3K) significantly prevented the beneficial effects of selenium on the BBB, whereas insulin-like growth factor 1 (a PI3K activator) mimicked the effects of selenium. In conclusion, the present findings indicated that selenium can inhibit autophagy by regulating the PI3K/AKT/mTOR signaling pathway, significantly preventing BBB damage following cerebral I/R injury in hyperglycemic conditions.

The effect of fullerenols on streptozotocin-induced diabetic rats

We support the general understanding that deleterious effects induced by hyperglycemia in rats would be alleviated by means of antioxidant treatment. Also, we have been supported and encouraged by many explorations on the usage of fullerenols for treating diabetic complications. Our present study aims to examine the potentials of fullerenols against diabetes in streptozotocin-induced diabetic rats. Animals were intraperitoneally administered with fullerenols for 15 days and then sacrificed. Following parameters were assessed: blood glucose, insulin concentration, levels of redox-related parameters, liver and kidney function biomarkers, glycogen contents, carbohydrate metabolic enzyme activities and histopathological analysis. As expected, fullerenols exhibited the well-known anti-oxidative property via decreasing MDA, increasing SOD, GSH-Px and CAT levels. Fullerenol treatment also showed a slight improvement in liver and kidney functional biomarkers, inferring a marginal hepatorenal protection. However, there were insignificant changes in levels of blood glucose, insulin, the pathological state of the necrotic islets. Herein, our results revealed that fullerenols failed to improve the function of pancreas and reverse the hyperglycemia in streptozotocin-induced diabetic rats in spite of a potent antioxidant role. Our study suggested that neither diabetes nor its complications could benefit from fullerenol administration.

Synthesis of a novel glibenclamide-pioglitazone hybrid compound and its effects on glucose homeostasis in normal and insulin-resistant rats

A new library of hybrid compounds that combine the functional parts of glibenclamide and pioglitazone was designed and developed. Compounds were screened for their antihyperglycemic effects on the glucose tolerance curve. This approach provided a single molecule that optimizes the pharmacological activities of two drugs used for the treatment of diabetes mellitus type 2 (DM2) and that have distinct biological activities, potentially minimizing the adverse effects of the original drugs. From a total of 15 compounds, 7 were evaluated in vivo; the compound 2; 4- [2- (2-phenyl-4-oxo-1,3-thiazolidin-3-yl) ethyl] benzene-1-sulfonamide (PTEBS) was selected to study its mechanism of action on glucose and lipid homeostasis in acute and chronic animal models related to DM2. PTEBS reduced glycemia and increased serum insulin in hyperglycemic rats, and elevated in vitro insulin production from isolated pancreatic islets. This compound increased the glycogen content in hepatic and muscular tissue. Moreover, PTEBS stimulated the uptake of glucose in soleus muscle through a signaling pathway similar to that of insulin, stimulating translocation and protein synthesis of glucose transporter 4 (GLUT4). PTEBS was effective in increasing insulin sensitivity in resistance rats by stimulating increased muscle glucose uptake, among other mechanisms. In addition, this compound reduced total triglycerides in a tolerance test to lipids and reduced advanced glycation end products (AGES), without altering lactate dehydrogenase (LDH) activity. Thus, we suggest that PTEBS may have similar effects to the respective prototypes, which may improve the therapeutic efficacy of these molecules and decrease adverse effects in the long-term.

Evaluation of testicular glycogen storage, FGF21 and LDH expression and physiological parameters of sperm in hyperglycemic rats treated with hydroalcoholic extract of Securigera Securidaca seeds, and Glibenclamide

Structural and physiological changes in sperm and semen parameters reduce fertility in diabetic patients. Securigera Securidaca (S. Securidaca) seed is a herbal medicine with hypoglycemic, antioxidant, and anti-hypertensive effects. The question now is whether this herbal medicine improves fertility in diabetic males. The study aimed to evaluate the effects of hydroalcoholic extract of S. Securidaca seeds (HESS), glibenclamide and a combination of both on fertility in hyperglycemic rats by comparing histological and some biochemical changes in testicular tissue and sperm parameters. The treatment protocol included administration of three doses of HESS and one dose of glibenclamide, as well as treatment with both in diabetic Wistar diabetic rats and comparison of the results with untrated groups. The quality of the testicular tissue as well as histometric parameters and spermatogenesis indices were evaluated during histopathological examination. Epididymal sperm analysis including sperm motility, viability, abnormalities, maturity, and chromatin structure were studied. The effect of HESS on the expression of LDH and FGF21 genes and tissue levels of glycogen, lactate, and total antioxidant capacity in testicular tissue was investigated and compared with glibenclamide. HESS improved sperm parameters in diabetic rats but showed little restorative effect on damaged testicular tissue. In this regard, glibenclamide was more effective than the highest dose of HESS and its combination with HESS enhanced its effectiveness so that histological tissue characteristics and sperm parameters were were comparable to those of healthy rats. The expression level of testicular FGF21 gene increased in diabetic rats, which intensified after treatment with HESS as well as glibenclamide. The combination of HESS and glibenclamide restored the expression level of testicular LDH gene, as well as tissue storage of glycogen, lactate and LDH activity, and serum testosterone to the levels near healthy control. S. Securidaca seeds can be considered as an effective supplement in combination with hypoglycemic drugs to prevent infertility complications in diabetes.

Anti-diabetic potential of Plectranthus lanuginosus in streptozotocin-induced diabetic rats

Purpose: To determine the antidiabetic effect of methanol extract of Plectranthus lanuginosus leaves in streptozotocin-induced hyperglycemic (HGD) rats.&#x0D; Methods: P. lanuginosus leaves were collected from Saad Medhas, Al Baha, Kingdom of Saudi Arabia. After defatting with n-hexane, they were extracted in vacuo at 40 oC with 75 % methanol. Streptozotocin (50 mgkg−1, i.p.) was used to induce hyperglycemia (diabetes) in the rats. The HGD rats received either standard drug (glibenclamide, 10 mgkg−1, p.o.) or Plectranthus lanuginosus leaf methanol leaf extract (PLLM) at doses of 200 and 400 mgkg−1/day, p.o. for 21 consecutive days. Blood samples were taken from the rat tails 2 h after dosing, and at 7-day intervals (i.e., 0, 7th, 14th and 21st days). The blood samples were used for measurement of fasting blood glucose (FBS), using a glucometer. On the 21st day, the rats were sacrificed via cardiac puncture. The activities of liver marker enzymes (SGPT and SGOT), and serum lipid profile (cholesterol, triglycerides, HDL and LDL) were determined using a hemolyzer.&#x0D; Results: Streptozotocin treatment produced significant hyperglycemia in the rats (348.9 ± 5.6) when compared to control (79.2 ± 1.3). However, PLLM (200 and 400 mg kg−1) produced significant and dose-dependent anti-diabetic (166.4 ± 5.6 and 123.86 ± 6.8 respectively) and antihyperlipidemic effects in HGD rats, at levels similar to those produced by the standard drug, glibenclamide (120.6 ± 6.4).&#x0D; Conclusion: P. lanuginosus leaf extract possesses pronounced anti-diabetic and anti-hyperlipidemic properties which may be due to the presence of phenolic and flavonoid constituents in the plant. Therefore, the plant extract can be further developed for the management of diabetes

Design, optimization, and in-vivo hypoglycaemic effect of nanosized glibenclamide for inhalation delivery

The aim of this research was the development and optimization of nanoniosomes for delivery of glibenclamide (Gbn) as hypoglycaemic agent to the lung in an inhaler dosage form. Fifteen formulae of niosomal dispersions were prepared according to Box–Behnken design. The effect of drug amount, Cholesterol molar ratio, and Hydrophilic lipophilic balance (HLB) values of the surfactant on the mean vesicle size, Zeta potential (ZP), polydispersity index (PDI), entrapment efficiency, and in-vitro released of Gbn were investigated. A quality control check was performed on an inhaler filled with the optimum nanoniosomal formula. The in-vivo hypoglycaemic effect of nanoniosomal inhalation was also evaluated. The vesicle size observed of the optimized formula was 172 ± 4.6 nm, PDI was 0.304 ± 0.06 and ZP was −49.9 ± 1.5 mv with 69 ± 9.3% in-vitro drug release after 2 h. The Cholesterol molar ratio and the HLB value showed a statistically significant effect on dependent variables. In-vivo results proved that nanoniosomes were efficiently delivered from the inhalation canister showing a mass median aerodynamic diameter of 1.4 micron. The inhaled nanoniosomal dispersion loaded with Gbn showed a decrease in blood glucose level of hyperglycaemic rats by 51.42 ± 5.2%± after 180 min which was nearly two folds compared to oral Gbn. Gibenclamide nanoniosomes inhaler could be suggested as a novel effective dosage form for the treatment of Diabetes mellitus.

THE EFFECT OF ADMINISTERING AFRICAN BITTER LEAF EXTRACT ON SPERMATOGENIC CELLS OF HYPERGLYCEMIC WISTAR RATS

Introduction: Diabetes is still a world health problem that can cause many complications. Male infertility is one of the diabetic complications. This condition is caused by oxidative stress in diabetic patients. African bitter leaf is believed to contain an antioxidant compound that can repair male infertility. Purpose: This study aims to determine the effect of administering African bitter leaf extract on spermatogenic cell count in hyperglycemic Wistar rats. Method: This study use Rattus norvegicus as an animal model, which was administrated with alloxan to induce hyperglycemic. P0 group were given Na CMC 0,1%, Control group were given glibenclamide 0,63/kg bodyweight for 14 days. 100mg/kg bodyweight (P1), 200mg/kg (P2), and 400mg/kg (P3) of African bitter leaf extract were administrated for 14 days. In the end, the animals were sacrificed, and testicle histopathologic sections were made. Results: Significant result (P&lt;0,05) comparing spermatogonium, primary spermatocyte, and spermatid count between groups. Post-hoc test shows the significant result on comparison of primary spermatocyte and spermatid count between P0 and P1. Conclusions: There is an effect of bitter leaf extract administration on spermatogenic cell count in hyperglycemic Wistar rats. The best improvement can be observed in the P1 group, administered with 100mg/kg bodyweight African bitter leaf.

Chemical and Biological Studies on the Goldenberry (Physalis peruviana L.) on Hyperglycemic Rats

The aim this investigate was to see if the medicine goldenberry fruits (Physalis peruviana L.) could help lower blood sugar, cholesterol, and triglycerides. The results of the chemical composition of goldenberry fruits were found to be a high source of antioxidants and which contain a high level of hypoglycemic and hypocholesterolemic such as phenolic compounds, ascorbic acid and ꞵ-carotenoid. The results showed that dried goldenberry fruits powder could be added to replace up to 5 and 10 % of hyperglycemic -diet respectively. Experimental hyperglycemic rats were fed for six weeks on diet contain dried goldenberry at extent 5% or 10% except normal control (G1) was fed on basal diet. Hyperglycemic rats fed on diets substituted in a part with 5% and10 % dried goldenberry the results showed that supplementing the hyperglycemic-producing diets with the additive goldenberry had significant decrease in serum glucose, lipid profile (cholesterols, triglyceride, low density lipoprotein LDL and very low density lipoprotein vLDL-cholesterol). Meanwhile, high density lipoprotein HDL cholesterol increased with all treatments, significant reduction in alanine aminotransferase ALT, aspartate aminotransferase AST, alkaline phosphatase ALP, and total bilirubin values, in respect to positive control were also observed.

Effects of mixture powder of black rice (Oryza sativa L indica), red beans (Phaseolus vulgaris L), and moringa leaves (Moringa oleifera L) on blood glucose concentration in hyperglycemic Rats

Background: Diabetes mellitus, increased blood glucose or hyperglycemia, is associated with increased oxidative stress and cardiovascular diseases. This condition will further cause carbohydrate and fat metabolism change, resulting in the decreased antioxidant defense system. Black rice, red beans, and moringa leaves contain oleic acid, butyric amino acid, antioxidants, phytic acid, and arginine, which can improve insulin sensitivity, and blood glucose homeostasis.Objective: This study aimed to analyze the effect of betamelor (black rice, red beans, and moringa leaves) on blood glucose in ratsMaterials and Methods: The design of this research was experimental research with pre-and post-control group design. A total of 20 Sprague Dawley female rats were divided into four groups, namely standard feed (PS), 80% feed of betamelor (PB8), 50% feed of betamelor (PB5), and 20% feed of betamelor (PB2). Betamelor intervention was given as much as 5% of weight for 28 days. Fasting Blood Glucose (FBG) levels were measured using the GOD-PAP method. Blood glucose data were analyzed by Analysis of Variance (ANOVA) at a 95% confidence level and using Duncan's test.Results: There were differences in FBG between groups after the intervention of betamelor. The results showed that after 28 days of intervention, betamelor decreased the serum glucose concentration from 122.69 mg / dL to 97.70 mg / dL (20.37%) in the PB8 group and from 123.91 mg / dL to 113.28 mg / dL (8.58%) in the PB5 group, but the standard diet (PS) increased by 5.73%. This result can be applied to reduce blood glucose levels in obese and patients with metabolic syndrome.Conclusions: There was a significant effect of giving a mixture of black rice, red beans, and Moringa leaves on fasting blood sugar in rats.

Alloxan as a better option than streptozotocin for studies involving painful diabetic neuropathy

Previous data indicate that the diabetogenic substance streptozotocin might act in nociceptive neurons changing the sensory signal, regardless of hyperglycemia. In the present article the effects of streptozotocin were compared with another diabetogenic drug, alloxan, for diabetes induction in rats. A possible direct effect of these drugs was tested by means of in vivo experiments and in vitro assays using cultured primary nociceptive neurons. Streptozotocin (17.5 and 35 mg/kg), alloxan (15 and 30 mg/kg) or vehicle were injected in adult male rats and the animal groups were separated according to glycemic levels. Body mass, glycemia and paw mechanical sensitivity were evaluated for 5 weeks. Streptozotocin caused an increase in mechanical sensitivity in both hyperglycemic and normoglycemic rats, while alloxan induced mechanical sensitization only in hyperglycemic animals. Injection of both substances induced local inflammation at rat paws; however, only streptozotocin caused significant mechanical sensitization when injected near to sensory neurons at the dorsal root ganglia. Also, streptozotocin treatment induced a reduction in intracellular calcium levels and inhibited capsaicin induced calcium transients and membrane depolarization. Alloxan did not affect calcium levels or membrane potential in primary nociceptive neurons. These findings suggest that alloxan might be a better option for animal studies regarding painful diabetic neuropathy as streptozotocin directly affects nociceptive neurons, probably by modulating TRPV1 channel activation.

Contribution of fasting and postprandial glucose-lowering mechanisms to the acute hypoglycemic effect of traditionally used Eryngium cymosum F.Delaroche

Ethnopharmacological relevanceEryngium cymosum F. Delaroche was detected as a traditional remedy against type 2 diabetes consumed by patients of Tlanchinol in the state of Hidalgo, Mexico. Aim of the study. Assessing the hypoglycemic effect and safety of the traditional extract of E. cymosum and relating it to key glucose-lowering mechanisms both in fasting and postprandial state. Materials and methodsThe aqueous extract of E. cymosum was subjected to HPLC analysis to identify its main components. Hyperglycaemic STZ-NA Wistar rats were administered with the extract to evaluate its effect on blood glucose levels and a possible dose-dependence. Afterward, it was evaluated in both pyruvate and maltose tolerance tests in STZ-NA rats to characterize its effect on gluconeogenesis and carbohydrate breakdown, two of the main mechanisms responsible for fasting and postprandial hyperglycaemia in type 2 diabetes patients. In addition, the inhibitory capacity of the extract was evaluated on key enzymes involved in gluconeogenesis and a-glucosidases. Moreover, insulin concentrations were measured in normoglycemic rats in both conditions to establish a link between the hypoglycaemic effect of the extract with insulin release and functioning. ResultsCaffeic acid (1), chlorogenic acid (2), and rosmarinic acid (3) were identified as the main constituents of the aqueous extract of E. cymosum, which exerted a hypoglycaemic effect in hyperglycaemic STZ-NA rats. It has a significant antihyperglycemic effect in the pyruvate tolerance test, and it was able to reduce the postprandial hyperglycaemia in maltose tolerance tests significantly. Moreover, it effectively reduced the activity of both gluconeogenic enzymes reaching almost 100% of inhibition, while it presented a modest 32% inhibition of aglucosidases. On the other hand, the extract decreased insulin levels after its oral administration in healthy rats in both nutritional states, without affecting normoglycemia in normal curves and reducing the postprandial peak in glucose load curves. ConclusionsThe traditional consumed form of aerial parts of E. cymosum is safe and regulated glucose levels both in fasting and in postprandial state.

Biological activity of 2α,3β,23-trihydroxyolean-12-ene on glucose homeostasis

We studied the effect and the mechanisms of action of 2α,3β,23-trihydroxyolean-12-ene (THO), from Croton heterodoxus Baill. (Euphorbiaceae), in glucose uptake in hyperglycemic rats. The effect of in vivo pretreatment with THO in hyperglycemic rats was analyzed. The in vitro effects of THO were observed in adipocytes and in adipose tissue. THO reduced glycemia, in part by increasing serum insulin and augmenting the disposal of glucose as glycogen in hepatocytes but did not change the serum concentration of glucagon-like peptide-1. THO increased glucose uptake in adipocytes and in adipose tissue by a mechanism dependent on phosphatidylinositol 3-kinase vesicular traffic and on the process of vesicle fusion at the plasma membrane in regions containing cholesterol, indicating the involvement of glucose transporter-4 (GLUT4). This triterpene may act solely via the activation and translocation of GLUT4 (rather than via nuclear actions, such as upregulation of GLUT4 synthesis), since THO did not alter the amount of GLUT4 mRNA or the content of GLUT4. Consistent with these data, the stimulatory effect of this triterpene on the quantity of GLUT4 in the membrane fraction was dependent upon p38 phosphorylation. In this experimental model, orally administered 10 mg/kg THO did not modulate extracellular serum lactate dehydrogenase. In conclusion, THO decreases hyperglycemia by increasing serum insulin and hepatic glycogen content. The THO mechanism of action on adipose tissue for glucose uptake is suggested to be via GLUT4 translocation stimulation mediated by a p38-dependent mechanism. THO is a potential antihyperglycemic agent that acts in a target tissue for glucose homeostasis.

Antihyperglycemic Activity of The Ethanolic Extract of the Bark of Mitragyna Ciliata (MYCA) in Albino Induced Diabetic Rats

Background: Diabetes an epidemic that gives rise to an increased macro vascular complication mortality rate of 1.5 million annually, increasing by 2035. Treatment of diabetes is complicated and associated with a severe side effect.&lt;/p&gt; &lt;p&gt;Objective: To evaluate the antihyperglycemic property of the ethanolic extract of the back of MYCA and its toxicological effect on the hematological parameters with histopathological analysis of selected organs of induced diabetic albino rats.&lt;/p&gt; &lt;p&gt;Method: The ethanoic extract (1000 mg/kg bw and 500mg/kg bw) and glibenclamide (0.5mg/kg bw) were administered to diabetic induced rats. The effect of the extract on the hematological was studied in the diabetic induced rats. Histopathological changes were observed in the liver of induced diabetic rats after the administration of the MYCA extract.&lt;/p&gt; &lt;p&gt;Results: The anti-hyperglycaemic effect was observed at two different levels, for two different doses (1000mg/kg and 500mg/kg). The results also showed significant suppression of blood glucose level in glucose fed hyperglycaemic albino rats but showed no significantly suppressed glucose level in overnight fasted normoglycemic rats.&lt;/p&gt; &lt;p&gt;Conclusion: The findings revealed that the ethanolic extract of MITRAGYNA CILIATA (MYCA) possess antihyperglycemic property. Besides, the extract can prevent the various complication of diabetes and improve some hematological parameters.

N-acetylcysteine supplementation did not reverse mitochondrial oxidative stress, apoptosis, and inflammation in the salivary glands of hyperglycemic rats

Background/objectivesPrevious studies have shown that N-acetylcysteine (NAC) supplementation with the simultaneous inclusion of HFD prevents salivary glands from oxidative stress and mitochondrial dysfunction. In this experiment, we examined if NAC supplementation could reverse the harmful effect of HFD on mitochondrial function, reduce the severity of apoptosis, and the activity of pro-oxidative enzymes in the salivary glands of rats with confirmed hyperglycemia.Subjects/methodsWistar rats were fed the standard or high-fat (HFD) diet for 10 weeks. After 6 weeks of the experiment, HFD rats were diagnosed with hyperglycemia and for the next 4 weeks, the animals were given NAC intragastrically. In the mitochondrial fraction of the parotid (PG) and submandibular salivary glands (SMG), we assessed redox status, inflammation, and apoptosis.ResultsThe inclusion of NAC increased the activity of mitochondrial complexes I and II + III as well as decreased the concentration of interleukin-1β, tumor necrosis factor α, and caspase-3, but only in the parotid glands of rats with hyperglycemia compared to the HFD group. However, N-acetylcysteine supplementation did not reduce the activity of caspase-9 or the Bax/Bcl-2 ratio in PG and SMG mitochondria. In both salivary glands we observed reduced activity of cytochrome c oxidase, NADPH oxidase, and xanthine oxidase, as well as hindered production of ROS and lower ADP/ATP radio, but the levels of these parameters were not comparable to the control group.ConclusionsWe demonstrated that NAC supplementation restores the glutathione ratio only in the mitochondria of the submandibular salivary glands. The supply of NAC did not significantly affect the other measured parameters. Our results indicate that NAC supplementation provides little protection against free radicals, apoptosis, and inflammation in the salivary gland mitochondria of HFD rats. Stimulated salivary secretion in hyperglycaemic rats supplemented with NAC seems to be closely related to mitochondrial respiratory capacity and appropriate ATP level.

Hypoglycemic effects of Enhydra fluctuans aerial extract on alloxan-induced diabetic rats

Enhydra fluctuans is one of the medicinal plants of the Minangkabau tribe, West Sumatra, Indonesia which is widely used by the community to treat various diseases including diabetes mellitus. However, scientific studying of its hypoglycemic activity is very limited. In this study, we evaluated the hypoglycemic activity of E. fluctuans aerial ethanol using an oral glucose tolerance test (OGTT) in stable hyperglycemia rats and its phytochemical screening. Twenty-five diabetic rats were divided into five groups with five replications: negative control, positive control (glibenclamide), ethanol extract dosage of 250, 500, and 1000 mg/kg. Blood glucose is measured at 0, 30, 60, 120, and 180 minutes. Blood glucose level, the area under the curve (AUC) value, and the percentage of blood glucose reduction is calculated. It was found that a dosage of 500 mg/kg was the best hypoglycemic activity in stable hyperglycemia rats and significantly different (p<0.05) compared with the negative control. Hypoglycemic activity of this dosage was longer if compared with glibenclamide. E. fluctuans aerial ethanol extract contained saponins, phenolic, terpenoids, steroids, and coumarin compounds. Our findings demonstrate that E. fluctuans have potent hypoglycemic effects in diabetes.

Effect of hyperglycemia on microglial polarization after cerebral ischemia-reperfusion injury in rats

Hyperglycemia has been shown to aggravate ischemic brain damage, in which the inflammatory reaction induced by hyperglycemia is involved in the worsening of cerebral ischemia-reperfusion injury. However, the role of microglial polarization in hyperglycemia-aggravating cerebral ischemia-reperfusion injury remains unknown. The present study investigated whether diabetic hyperglycemia inhibited or activated microglia, as well as microglial subtypes 1 and 2. Rats were used to establish the diabetic hyperglycemia and middle cerebral artery occlusion (MCAO) model. The markers CD11b, CD16, CD32, CD86, CD206, and Arg1 were used to show M1 or M2 microglia. The results revealed increased neurological deficits, infarct volume, and neural apoptosis in rats with hyperglycemia subjected to MCAO for 30 min and reperfused at 1, 3, and 7 days compared with the normoglycemic rats. Microglia and astrocyte activation and proliferation were inhibited in hyperglycemic rats. Furthermore, M1 microglia polarization was promoted, while that of M2 microglia was inhibited in hyperglycemic rats. These findings suggested that the polarization of M1 and M2 microglia is activated and inhibited, respectively, in hyperglycemic rats and may be involved in the aggravated brain damage caused by ischemia-reperfusion in diabetic hyperglycemia.

Efficacy Trials of Sorghum based Composite Flour Mix on the Blood Glucose Levels of Experimental Induced Hyperglycemic Rats

Diabetes is global health disorder affecting millions of people worldwide with the largest number of diabetic adults in India ranging around 61.3 million people. Use of indigenous foods has been advocated to reduce the incidence of chronic, diet related non-communicable diseases such as diabetes, obesity and CVD. In the present study an approach was made to develop and assess the functional efficacy of sorghum based composite flour mix for a period of 15 days on blood glucose level of alloxan induced diabetes rats. Out of all the seven groups, Group A showed no significant improvement in the blood sugar level at the end of the supplementation period, Group B showed significant increase in the blood glucose level while Group C showed significant decrease in the blood glucose level along with Groups D, E, F and G fed with sorghum based composite flour mix showed significant decrease in the blood sugar level. Thus it can be concluded that the blood glucose lowering effect of sorghum based composite flour may be due to the in situ composition of the composite flour mix which are potential sources of dietary fibres like cellulose, lignin, phytonutrients including tannins, phenolic acids, anthocyanins, phytosterols, polyphenols, and policosanols.

Kalanchoe daigremontiana: Functional Properties and Histopathological Effects on Wistar Rats under Hyperglycemia-inducing Diet

Abstract: Introduction: Diabetes is a worldwide pandemic disease with an expensive way of control. Locals around the world have been used botanical extracts to reduce the effects of this deadly disease to improve the quality of life of the patients. Objectives: To evaluate the effects of crude extracts of the ethnobotanical species K. daigremontiana on a hyperglycemia rat model to support its antidiabetic use in traditional medicine. Materials and Methods: Crude leaves extract were daily administered per os to Wistar rats for six months. Hyperglycemic induction model was rich-sucrose diets. Six animals per group were used: i) standard diet, ii) sucrose-rich diet, iii) sucrose-rich diet + extract (1 ml), iv) sucrose-rich diet + extract (2 ml) and v) standard diet + extract (2 ml). All animals were sacrificed and the liver prepared for histopathological analysis. Powdered leaves were functionally characterized and analyzed by Fourier Transform Infrared (FTIR) spectroscopy. Results: Treatment with 2 ml of the crude extract caused the least tissue damage, compared to the control. A high antioxidant activity (DPPH: 111.14 μM Trolox equivalents g-1 dry weight (DW); ABTS: 223.90 μM Trolox equivalents g-1 DW) was observed. A content of 0.54 mg ascorbic acid g-1 DW, total phenol content of 17.45 mg gallic acid g-1 DW and flavonoid content of 2.3 mg equivalent quercetin g-1 DW were determined. No conclusive evidence on the molecules present in the extract was obtained by FTIR spectroscopy. Conclusion: The use of dosages of 2 ml of crude extract of Kalanchoe daigremontiana reduces liver damage under high sucrose conditions. Key words: Traditional medicine, Anti-hyperglycemic, Diabetes Sucrose-rich diet, Kalanchoe daigremontiana, Phytotherapy.