Diabetes mellitus is a metabolic disorder caused by insulin deficiency, insulin resistance, genetic alterations, and oxidative stress. The high glucose levels may impair the functioning of nerve cells, leading to neurodegenerative diseases, including cognitive impairment. Clitoria ternatea has various pharmacological activities, including antioxidant, anti-inflammatory, antidiabetic, and neuroprotective effects. The present study evaluates the efficacy of fresh flower aqueous extract of Clitoria ternatea against diabetes-induced cognitive impairment. The challenges in delivering drugs targeting the brain possess the limitations of crossing the blood-brain barrier. Metal nanoparticles are considered the most reliable brain drug delivery systems. Considering the neurotoxicity of cobalt oxide, whether it can be used to improve brain delivery is also evaluated. Cobalt oxide nanoparticles (Co3O4 NPs) of fresh flower aqueous extract of Clitoria ternatea are prepared by green synthesis and characterized. The effect of these nanoparticles is compared with Clitoria ternatea extract against Streptozotocin (STZ)-induced cognitive impairment. The behavioral, biochemical, in vivo antioxidant, total thiol content, estimation of proinflammatory cytokines, acetylcholine esterase, and nitrite levels in the brain of STZ-induced diabetic rats revealed that cobalt oxide nanoparticles showed neurotoxicity, whereas C. ternatea showed neuroprotective effect and also improved the cognitive function. The lower dose of cobalt oxide nanoparticles of C. ternatea (2 mg/kg) exhibited a neuroprotective and cognition improvement effect. However, the higher dose (4 mg/kg) of cobalt oxide nanoparticles of C. ternatea showed a neurotoxic effect. Since Co3O4 NPs are neuroprotective at low doses, they can be used for neuroprotective actions. However, dose optimization studies are required.

We compared 2 models of metabolic syndrome in rats: high-fat diet (58% calories) with single streptozotocin injection at a dose of 25 mg/kg and replacement of water with 20% fructose solution. The model with fructose solution did not cause the main signs of metabolic syndrome over 24 weeks: concentrations of glucose, triglycerides, cholesterol, weight, and BP did not significantly differ from the control group (standard diet). At the same time, single streptozotocin administration was followed by the development of persistent hyperglycemia, hypertriglyceridemia, hypercholesterolemia, and signs of visceral obesity. High-fat diet combined with injection of streptozotocin in a low dose can be considered a more representative model of metabolic syndrome in humans.

BACKGROUND: Depression is a multifaceted disorder that represents one of the most common causes of disability. The risk for developing depression is increased in women and among individuals with chronic diseases. For example, individuals in the United States with diabetes mellitus (DM) are at a twofold increased risk of developing depression compared to the general population and approximately one-quarter of women with diabetes have comorbid depression. The neurobiological mechanisms underlying this association between diabetes and depression is not fully understood and is particularly under-investigated in female models. We sought to explore the role of neuroinflammation in diabetes-induced depression in a female mouse model of hyperglycemia.
METHODS: To this end, we utilized female C57BL/6 J mice to (1) characterize the depressive-like symptoms in response to 75 mg/kg/day dose of streptozotocin (STZ) over 5 days, a dose reported to induce hyperglycemia in female mice (n=20), (2) determine if female hyperglycemic mice are sensitized to unpredictable chronic mild stress (UCMS)-induced depressive-like behavior and neuroinflammation (n=28), and (3) investigate if female hyperglycemic mice are primed to respond to a subthreshold dose of lipopolysaccharide (LPS), an acute inflammatory challenge (n=21).
RESULTS: Our results demonstrate that female mice exhibit robust hyperglycemia but limited evidence of depressive-like behavior in response to 75 mg/kg STZ. Additionally, we observe that healthy female mice have limited response to our stress protocol; however, hyperglycemic mice display increased stress-sensitivity as indicated by increased immobility in the forced swim test. While STZ mice show evidence of mild neuroinflammation, this effect was blunted by stress. Further, STZ mice failed to display a sensitization to inflammation-induced depressive-like behavior.
CONCLUSIONS: We interpret this data to indicate that while STZ-induced hyperglycemia does increase vulnerability to stress-induced depressive-like behavior, this effect is not a consequence of neuroinflammatory priming. Future studies will seek to better understand the mechanisms underlying this sensitization.

BACKGROUND: Alzheimer\'s disease is the most common neurodegenerative disease with therapeutic limitations. Insulin resistance plays a role in the progression of Alzheimer\'s disease. Therapies that modulate insulin secretion and signaling, as well as oxidative stress in the brain are now being investigated for their potential role in the prevention of Alzheimer\'s disease (AD). Terminalia macroptera (Combretaceae) is a plant that different parts have been used traditionally for the treatment of metabolic and neurological conditions. Previous study has indicated that the crude extract exhibit anti-diabetic property. In addition, the plant is a rich source of tannins, phenolic acids, flavonoids, triterpenes. However, there is no study on its protective effect against biochemical alterations of AD in diabetic rats.
OBJECTIVE: The present research study investigated the neuroprotective effects of TeMac™ on Alzheimer-like pathology induced by aluminum chloride (AlCl3) in diabetic rats.
METHODS: A phytochemical analysis of TeMac™ was carried out to quantify tannins. The potential effect of the tannins-enriched fraction (TEF) of TeMac™ to prevent the formation of senile plaques was conducted by its ability to inhibit the activities of β-secretase (EC 3.4.23.46), monoamine oxidase A (EC 1.4.3.4) and the fibrillation of Aβ. A diabetic model was induced from female Wistar rats by a single intraperitoneal injection of streptozotocin (STZ, 35 mg/kg BW). After that, the blood glucose level was measured to confirm the induction of diabetes. Three days after induction, animals received AlCl3 (75 mg/kg BW) alone (AD control) or concomitantly with 400 mg/kg BW of TEF of TeMac™ or 5 mg/kg BW Daonil by daily gavage for 42 days. At the end of the experiment, rats were sacrificed, blood and brains were collected. The levels of amyloid fibrils, glucose, albumin and the activities of DPP4, β-secretase and phosphatase, and markers of oxidative stress in the brain were assessed.
RESULTS: TEF of TeMac™ displays a potential ability to inhibit the activities of β-secretase, monoamine oxidase, and Aβ fibrillation. Treatment with TEF of TeMac™ significantly inhibited DPP4 and BACE1 activities and reduced brain glucose and amyloid fibril levels, and improved cerebral albumin levels and modulated oxidative stress markers.
CONCLUSIONS: Our findings indicate that TEF of TeMac™ prevents Alzheimer\'s-type pathology linked to insulin resistance in rats. TEF of TeMac™ may be a potential drug candidate for the treatment of diabetes-associated cognitive impairment.

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The aims of this study were to examine the effects of pyridoxine administration on the activities of cardiac antioxidant stress enzymes superoxide dismutase (SOD) and catalase (CAT) and enzyme indicators of cardiometabolic status, lactate and malate dehydrogenase (LDH, MDH), as well as LDH and MDH isoforms\' distribution in the cardiac tissue of healthy and diabetic Wistar male rats. Experimental animals were divided into five groups: C1-control (0.9% sodium chloride-NaCl-1 mL/kg, intraperitoneally (i.p.), 1 day); C2-second control (0.9% NaCl 1 mL/kg, i.p., 28 days); DM-diabetes mellitus (streptozotocin 100 mg/kg in 0.9% NaCl, i.p., 1 day); P-pyridoxine (7 mg/kg, i.p., 28 days); and DM + P-diabetes mellitus and pyridoxine (streptozotocin 100 mg/kg, i.p., 1 day and pyridoxine 7 mg/kg, i.p., 28 days). Pyridoxine treatment reduced CAT and MDH activity in diabetic rats. In diabetic rats, the administration of pyridoxine increased LDH1 and decreased LDH4 isoform activities, as well as decreased peroxisomal MDH and increased mitochondrial MDH activities. Our findings highlight the positive effects of pyridoxine administration on the complex interplay between oxidative stress, antioxidant enzymes, and metabolic changes in diabetic cardiomyopathy.

Introduction: Propolis has a wide range of biological and pharmacological actions, including antioxidant properties-particularly its phenolic and flavonoid constituents-that could potentially protect the reproductive system from oxidative damage. Method: Four groups were allocated 40 male Wistar rats each. The vehicle was given to the first group\'s normal control rats negative control. The second, third, and fourth groups of diabetic rats were given vehicle (diabetic control) and propolis orally at 50 and 100 mg/kg, respectively, for 8 weeks. Diabetes was induced in rats via injection of nicotinamide and streptozotocin (STZ). Fasting blood glucose (FBG) and insulin levels, homeostatic model assessment for insulin resistance (HOMA-IR), and semen analysis were assessed. In addition, assessments of serum reproductive hormones, including total testosterone (TTST), estradiol (E2), follicle-stimulating hormone luteinizing hormone (LH), and prolactin (PRL), were measured at the end of the study. Tissue total testosterone, E2, and dihydrotestosterone were also evaluated. Serum and tissue oxidative enzymes, including catalase (CAT), superoxide dismutase, and glutathione peroxidase activities, were examined, and malondialdehyde content was determined. The pancreatic and testicular tissues were histopathologically examined, and proliferating cell nuclear antigen (PCNA) and B-cell lymphoma 2 (Bcl-2) in testicular tissue were immunohistochemically analyzed. Testicular tissue was examined for DNA integrity using a comet assay. Results: Compared to the STZ-control group, propolis greatly decreased FBG levels and improved the glycemic status of diabetic rats. In comparison to the STZ-DC group, propolis increased the number of sperm cells and the percent of morphologically normal and viable sperm in male rats, improving their fertility. Propolis also restored the pancreatic islets, protected the testis from oxidative stress, and increased levels of reproductive hormones in the blood, especially testosterone. Moreover, propolis at high doses demonstrated a strong positive response for Bcl-2 and a negative expression of proliferating cell nuclear antigen in spermatogenic cells. Conclusion: The data obtained strongly indicate that STZ causes severe impairments to the testis whereas propolis, acting as an antioxidant, protects against the adverse effects of STZ on the testis.

Diabetic cardiomyopathy (DCM) is one of the serious complications of type 2 diabetes mellitus. Vasant Kusumakar Rasa (VKR) is a Herbo-metallic formulation reported in Ayurveda, an Indian system of medicine. The present work was designed to study the effect of VKR in cardiomyopathy in type 2 diabetic rats. Diabetes was induced by feeding a high-fat diet (HFD) for 2 weeks followed by streptozotocin (STZ) administration (35 mg/kg i.p.). VKR was administered orally at dose of 28 and 56 mg/kg once a day for 16 weeks. The results of the study indicated that VKR treatment significantly improved the glycemic and lipid profile, serum insulin, CK-MB, LDH, and cardiac troponin-I when compared to diabetic control animals. VKR treatment in rats significantly improved the hemodynamic parameters and cardiac tissue levels of TNF-α, IL-1β, and IL- 6 were also reduced. Antioxidant enzymes such as GSH, SOD, and catalase were improved in all treatment groups. Heart sections stained with H & E and Masson\'s trichome showed decreased damage to histoarchitecture of the myocardium. Expression of PI3K, Akt, and GLUT4 in the myocardium was upregulated after 16 weeks of VKR treatment. The study data suggested the cardioprotective capability of VKR in the management of diabetic cardiomyopathy in rats.

NSG mice are among the most immunodeficient mouse model being used in various scientific branches. In diabetelogical research diabetic NSG mice are an important asset as a xenotransplantation model for human pancreatic islets or pluripotent stem cell-derived islets. The treatment with the beta cell toxin streptozotocin is the standard procedure for triggering a chemically induced diabetes. Surprisingly, little data has been published about the reproducibility, stress and animal suffering in these NSG mice during diabetes induction. The 3R rules, however, are a constant reminder that existing methods can be further refined to minimize suffering. In this pilot study the dose-response relationship of STZ in male NSG mice was investigated and additionally animal suffering was charted by applying the novel \'Relative Severity Assessment\' algorithm. By this we successfully explored an STZ dose that reliably induced diabetes while reduced stress and pain to the animals to a minimum using evidence-based and objective parameters rather than criteria that might be influenced by human bias.

Cystic fibrosis-related diabetes (CFRD), the most common comorbidity in cystic fibrosis (CF), leads to increased mortality by accelerating the decline in lung function. Scnn1b-Tg transgenic mice overexpressing the epithelial sodium channel β subunit exhibit spontaneous CF-like lung disease, including airway mucus obstruction and chronic inflammation. Here, we established a chronic CFRD-like model utilizing Scnn1b-Tg mice made diabetic by injection of streptozotocin. In Ussing chamber recordings of trachea, Scnn1b-Tg mice exhibited larger amiloride-sensitive currents and forskolin-activated currents, without a difference in ATP-activated currents compared to wildtype (WT) littermates. Both diabetic WT (WT-D) and diabetic Scnn1b-Tg (Scnn1b-Tg-D) mice on the same genetic background exhibited substantially elevated blood glucose at 8 weeks; glucose levels also were elevated in bronchoalveolar lavage fluid (BALF) Bulk lung RNA-seq data showed significant differences between WT-D and Scnn1b-Tg-D mice. Neutrophil counts in BALF were substantially increased in Scnn1b-Tg-D lungs compared to controls (Scnn1b-Tg-con) and compared to WT-D lungs. Lung histology data showed enhanced parenchymal destruction, alveolar wall thickening, and neutrophilic infiltration in Scnn1b-Tg-D mice compared to WT-D mice, consistent with development of a spontaneous lung infection. We intranasally administered Pseudomonas aeruginosa to induce lung infection in these mice for 24 hours, which led to severe lung leukocytic infiltration and an increase in pro-inflammatory cytokine levels in the BALF. In summary, we established a chronic CFRD-like lung mouse model using the Scnn1b-Tg mice. The model can be utilized for future studies toward understanding the mechanisms underlying the lung pathophysiology associated with CFRD and developing novel therapeutics.