Serum Of Diabetic Rats Research Articles

Therapeutic role of Arabic gum against nicotinamide/streptozotocin-induced diabetes and nephropathy in Wistar rats

Background Chronic kidney disease is mainly caused by diabetic nephropathy and also causes a lot of suffering and death for people with diabetes, as one of the worst long-term complications. Arabic gum (AG) has been reported to have antioxidant, hypolipidemic and hypoglycemic effects. Objective The goal of this study was to scrutinize the antioxidant and anti-inflammatory roles of AG against nicotinamide (NA)/streptozotocin (STZ)-induced diabetic nephropathy in Wistar rats. Materials and methods The experiment involved three groups of 18 adult male Wistar rats (six each). The normal control group received 0.9% NaCl orally for 8 weeks. The diabetic group received NA intraperitoneal injection (120 mg/kg b.w.) followed by 60 mg/kg body weight (bw) STZ in citrate buffer (pH 4.5) after 15 min. After confirming the induction of diabetes, animals received 0.9% NaCl orally for 8 weeks. The AG-treated diabetic group received 20 mg AG/kg bw/day orally for 8 weeks after diabetes induction. Results and conclusion Diabetic rats exhibited hyperglycemia which was confirmed by increased levels of serum fasting glucose and fructosamine. Elevated serum urea, creatinine, uric acid, cystatin c, and sodium levels were noticed in the serum of diabetic rats while potassium levels were markedly reduced reflecting nephropathy. Oxidative stress was evident in the diabetic kidney, as indicated by increased malondialdehyde (MDA) and decreased reduced glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD). AG administration ameliorated elevated fasting blood glucose and serum fructosamine levels as well as the kidney function parameters in serum. AG also attenuated oxidative stress and increased antioxidant capacity in the diabetic kidney. Immune-inflammatory mediators, such as tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), and tumor suppressor protein (p53) expression were significantly upregulated in diabetic rats, but AG produced a downregulation of them. Thus, AG possesses an antidiabetic effect and has a nephropreventive effect that was manifested by a decrease of urea, creatinine, uric acid, cystatin c and sodium. AG also has anti-inflammatory and antioxidant effects and minimizes histopathological alterations in the kidneys of diabetic rats. Despite these ameliorative effects, the efficacy and safety of AG as an adjunct drug for diabetic kidney disease needs to be validated by more scientific research.

Effects of Berberis vulgaris fruit extract on oxidative stress status in the kidney and liver of diabetic rats.

Oxidative stress has a key role in the diabetes pathogenesis and complications. Berberis vulgaris is known in folk medicine for curing several diseases. The current research aimed to assess the influences of Berberis vulgaris fruit extract against oxidative stress in streptozotocin-induced diabetic rats. Streptozotocin (60 mg/kg, ip) was injected to male rats. After diabetes confirmation, animals received the Berberis vulgaris fruit extract daily at amounts of 3.5 and 7.5 % of drinking water (v/v) for six weeks. Total thiol and lipid peroxidation levels were assessed in the serum, liver, kidney and spleen at the end of the study. Diabetic rats exhibited hyperglycemia along with enhancement of lipid peroxidation levels in the serum, liver, kidney and spleen, and decrement of total thiol content in the kidney and liver tissues. Chronic administration of Berberis vulgaris fruit extract at amount of 3.5 % of drinking water decreased the lipid peroxidation level in the serum and liver, and enhanced total thiol level in the liver and kidney. Berberis vulgaris fruit extract exerts antioxidant activity in the serum, liver and kidney organs of diabetic rats. Therefore, it might be used in the prevention and control of diabetes complications.

Xylitol attenuates diabetes induced intestinal permeability changes and inflammatory injury by improving intestinal tight junction protein expression and mucus secretion in rats

ABSTRACT The purpose of this study was to investigate the protective effect of xylitol on gut mucosal barrier injury in a type 2 diabetes rat model. Treatment with xylitol not only ameliorated diabetic-induced changes to small intestinal mucosa morphology and decreased diamine oxidase concentration in the serum of diabetic rats, but also modified the inflammatory infiltrates and improved the secretory IgA levels of the small intestinal epithelium. Increased expression of zo-1, occludin, mucin-2 and intestinal trefoil factor also was detected in small intestinal tissue. Intragastric administration of xylitol suppressed diabetes-induced increases of myeloperoxidase, eosinophil peroxidase, IL-6 and TNF-α. These results suggest that xylitol reduces mucosal inflammatory lesions and improves the intestinal barrier in diabetic rats by maintaining the structural integrity of the mucous layer, inhibiting the expression of inflammatory mediators and enhancing the expression of tight junction proteins associated with intestinal permeability.

Mimosa pudica Linn. extract improves aphrodisiac performance in diabetes-induced male Wister rats

Male sexual dysfunction is considered one of the major consequences of diabetes mellitus. The medicinal plant, Mimosa pudica Linn. is believed to have numerous therapeutic effects, including anti-diabetic, anti-obesity, aphrodisiac, and a sexual behaviour-enhancing properties. In the present study, the significant effect of ethanolic extract of M. pudica L. to scavenge excessive free radicals and alleviate the deleterious effects of alloxan-induced diabetes on the male sexual system of rats was demonstrated. The rats treated with the M. pudica L. extract recovered their body weight, the weight of their reproductive organs, the characteristics of the sperm and the histocellular arrangement of the testes. In addition, significant levels of hormones (testosterone, follicle-stimulating hormone and luteinising hormone) increased in both serum and testicular homogenates of male diabetic rats treated with M. pudica L. extract. Further, antioxidant enzymes, SOD, CAT, GSH, and GPx levels are increased, and oxidative stress markers MDA and ROS are reduced in both serum and testicular homogenates of M. pudica L. extract treated male rats. Furthermore, an in silico molecular docking study was performed to predict high potential compounds of M. pudica L. extract against the PDE5 receptor. Two bioactive compounds, namely 3-Dibenzofuranamine (-11.1 kcal × mol−1), Stigmasta-7,16-dien-3-ol (-10.4 kcal × mol−1) showed the highest binding affinities with PDE5 enzyme, much higher than the reference drug sildenafil (-9.9 kcal × mol−1). According to these findings, bioactive compounds rich in ethanolic extract of M. pudica L. have significant aphrodisiac performance in diabetic rats. Communicated by Ramaswamy H. Sarma

Mitragyna Parvifolia- Effective Against Hyper Glycaemia, Proinflammatory Markers and Liver Apoptosis in Streptozotocin Induced Diabetic Rats

Background Ethanolic extract of Mitragyna pareidolia leaves were used as a traditionally use in the treatment of diabetic conditions. The aim of the current study was to find out the effect of Mitragyna pareidolia ethanolic leaves extract (MPE) on hyperglycemia developed by streptozotocin (STZ) induced type 2 diabetes in rats. Materials and Method An animal model of diabetes type 2 was developed by administration of STZ 90 mg/Kg to two-day old neonatal rat pups. Oral glucose test and parameters were examined of diabetic rat after the different dose of extracts. The rats were existing into following groups: Group I –Normal control, Group II – STZ diabetic control, Group III –STZ Diabetic –orally administered MPEx at doses of 300 mg/kg, Group IV STZ-Diabetic – orally administered at doses of 500 mg/kg, Our study was confirmed that 8 weeks chronic treatment with MPE in a dose dependent manner (300 and 500 mg/kg) reduced hyperglycemia and significantly increased serum insulin, C-peptide. Histology of liver was performed after sacrificing the rats with euthanasia. Result The ethanolic extract of MP was not show any acute toxicity up-to the dose of 2000 mg/kg and it was shown better glucose consumption in oral glucose tolerance test. Orally treatment of different doses of MP leaves extract decreased the level of serum glucose, reduce elevated levels of tumor necrosis factor α (TNF-α), interleukin IL-6 in the serum of diabetic rats. After the study, we found that elevated blood glucose and lipids were bring back to near normal. In addition, MPE also reduce elevated levels of tumor necrosis factor α (TNF-α), interleukin IL-6 in the serum of diabetic rats. Conclusion We conclude that MPE exerted antidiabetic effects and reduced its associated complications such as dyslipidemia and inflammation. HE and confocal image of TUNEL assay showed that MPE reduced inflammation and apoptosis in diabetic rats.

The Potential Hepatoprotective Effect of Vaccinium arctostaphylos L. Fruit Extract in Diabetic Rat.

Vaccinium arctostaphylos has traditionally been employed in Iranian folk medicine to treat diabetes. However, the precise molecular mechanisms underlying its antidiabetic properties remain incompletely understood. The current experiment intended to explore the modulatory effects of V. arctostaphylos fruit ethanolic extract (VAE) on biochemical and molecular events in the livers of diabetic rats. In this experimental study, male Wistar rats were randomly assigned to four groups: normal control, normal rats with VAE treatment, diabetic control, and diabetic rats with VAE treatment. Following 42 days of treatment, the impact of VAE on diabetes-induced rats was assessed by measuring various serum biochemical parameters, including insulin, free fatty acids (FFA), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS), and adiponectin levels. The activities of hepatic carbohydrate metabolic enzymes and glycogen content were determined. Additionally, expression levels of selected genes implicated in carbohydrate/lipid metabolism and miR-27b expression were evaluated. H and E-stained liver sections were prepared for light microscopy examination. Treatment with VAE elevated levels of insulin and adiponectin that reduced levels of FFA, ROS, and TNF-α in the serum of diabetic rats. VAE-treated rats exhibited increased activities of hepatic glucokinase (GK), glucose-6-phosphate dehydrogenase (G6PD), and glycogen concentrations, in conjunction with decreased activities of glucose-6-phosphatase (G6Pase) and fructose-1,6-bisphosphatase (FBPase). Furthermore, VAE significantly upregulated the transcription levels of hepatic insulin receptor substrate 1 (Irs1) and glucose transporter 2 (Glut2), while considerably downregulated the expression of peroxisome proliferator-activated receptor gamma (Pparg) and sterol regulatory element-binding protein 1c (Srebp1c). VAE remarkably enhanced the expression of miR27-b in the hepatic tissues of diabetic rats. Abnormal histological signs were dramatically normalized in diabetic rats receiving VAE compared to those in the diabetic control group. Our findings underscore the hypoglycemic and hypolipidemic activities of V. arctostaphylos and assist in better comprehension of its antidiabetic properties.

Melatonin and probiotic administration ameliorated hyperglycaemia, oxidative stress, and enhanced cytoprotective effect on beta-cells of diabetic rats.

The study aimed at investigating the effects of administering melatonin and a probiotic to streptozotocin-induced diabetic rats on hyperglycaemia, oxidative stress biomarkers and beta-cells. Type 1 diabetes was induced in 5 months-old male Wistar rats by single intraperitoneal (i.p.) administration of freshly-prepared STZ (60mg/kg body weight). Six groups of 10 rats were used and treated once daily for six weeks; (1) Healthy control: normal saline only; (2) Pre-treated with Melatonin (MEL); (3) Diabetic control; (4) Diabetic + Treated with MEL; (5) Diabetic + Treated with Probiotic (Prob); (6) Diabetic + Treated with MEL + Prob. Blood glucose, body weight, activities of antioxidant enzymes and malondialdehyde concentration in serum and tissues, reduced glutathione and immunohistochemical assay. Data obtained were expressed as mean ± standard error of the mean (Mean ± SEM) and subjected to ANOVA followed by Tukey's post hoc test. Melatonin + Probiotic significantly decreased blood glucose concentrations in diabetic treated rats, compared to the diabetic control rats. MEL + Probiotic increased (p < 0.05) superoxide dismutase activity in serum and liver of diabetic rats. MEL + Probiotic reduced (p < 0.05) malondialdehyde concentration in the serum, liver and kidneys, respectively. MEL + Probiotic treated diabetic rats displayed islets with much greater content of insulin. Melatonin + Probiotic combination was more effective in mitigating hyperglycaemia, oxidative stress, and exerted cytoprotective effect on the beta-cells.

Safety and antidiabetic activity of Lagenaria siceraria (Molina) Standl. juice in streptozotocin -induced diabetic rats

Ethnopharmacological relevanceDiabetes and its complications have overwhelmed India's healthcare system. Current therapies are expensive and have adverse side effects, thus dietary changes and alternative treatments are needed. Lagenaria siceraria (Molina) Standl. Juice is used mainly for its nutritional and medicinal values, however toxicity of the juice and antidiabetic effects have been poorly characterized. Aim of the studyTo investigate the toxicity, anti-diabetic and anti-inflammatory efficacy of Lagenaria siceraria (Molina) Standl. (LS) juice. Materials and methodsIn vitro antidiabetic (α-glucosidase, α-amylase and DPP-4 inhibitory) activities were screened using standard procedures. The glucose uptake test was carried out by using L6 rat skeletal muscle cell line. In vivo sub-acute toxicity of LS juice was assessed on Wistar rats. Wistar rats were induced with diabetes by a single intraperitoneal (I.P) injection of freshly prepared streptozotocin (55 mg/kg body weight). The animals were randomly divided into 6 groups: normal control, untreated diabetic control, diabetic rats. Different dose of 200 mg/kg, 400 mg/kg and 600 mg/kg body weight of LS juice were administered, one group of diabetic rats were administered with 2 IU/mL insulin. The rats were sacrificed on the 31st day of the experiment and various in vivo biochemical parameters were evaluated in the serum and tissue homogenates of diabetic rats. ResultsSignificant dose-dependent inhibition of α-amylase (22.6%), α-glucosidase (50.13%), and DPP-4 (61.50%) activity was observed by LS juice. LS juice (10 μg/mL) increased insulin-mediated 2NBDG (2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) Amino)-2-Deoxyglucose) absorption in L6 cells. Animals treated with LS juice showed no toxicity or unfavorable pharmacological effects. Lagenaria siceraria (Molina) Standl. Juice improved glucose tolerance in diabetic rats with reduced fasting blood glucose. Lipopolysaccharide induced NF-κB, TNF-α and IL-1β production was also decreased in rats fed with LS juice. ConclusionLagenaria siceraria (Molina) Standl. Juice has demonstrated promising anti-inflammatory properties as well as the capacity to inhibit the digestion enzymes glucosidase and amylase. Our findings thus open new avenues for further research into the antidiabetic potential of LS juice.

How does l-theanine treatment affect the levels of serum and hippocampal BDNF, insulin and adipocytokines in diabetic rats?

BackgroundDiabetes Mellitus (DM), a metabolic disease characterized by the increased blood glucose level, insulin deficiency or ineffectiveness, may cause structural and functional disorders in the brain. l-Theanine (LTN) has the relaxing, psychoactive, antidepressant, anti-inflammatory and antinecrotic properties, and regulates the functions of hippocampus (HP) in brain. In the present study, the aim was to identify the effects LTN on the levels of BDNF, insulin and adipocytokines (TNF-α, leptin, adiponectin and resistin) in both HP and serum of diabetic rats. Methods32 male Wistar rats were divided into four groups (n = 8/group): Control, LTN, DM and DM + LTN. Diabetes was induced by by nicotinamide/streptozotocin. 200 mg/kg/day LTN treatment was applied for 28 days. The serum and hippocampal levels of the parameters were determined by using commercial ELISA kits. Additionally, HP tissues examined histopathologically. ResultsLTN treatment significantly decreased leptin and adiponectin levels in HP tissues in diabetic rats (p < 0.05). Although it decreased the insulin level in both serum and HP, this was not statistically significant. No significant effect on other parameters was observed (p > 0.05). In histopathological analysis, although the damage was reduced by LTN in all sections of HP, this change was significant mainly in CA3 region (p < 0.05). ConclusionIt was concluded that LTN has the ability to reduce hippocampal degeneration and modulates adipocytokines in diabetic rats.

The effect of progressive endurance training and extract of black winter truffle on proteins levels and expression of hippocampus α-synuclein and HSF1 in the healthy and diabetic rats

AimThe research aimed to investigate the effect of endurance running and T. Brumale extract on α-Syn and HSF1 in the brain and serum of healthy and diabetic rats. MethodsA total of 40 Wistar rats were randomly divided into eight groups: Control (C), Exercise (E), Control-Tuber (T), Exercise-Tuber (ET), Control-Diabetes (D), Exercise-Diabetes (ED), Control-Diabetes-Tuber (CDT), and Exercise-Diabetes-Tuber (EDT). The endurance running was carried out five times per week for five weeks. The hippocampus and the serum α-Syn and HSF1 were measured using an enzyme-linked immunosorbent assay method. ResultsThe brain α-Syn levels were higher in diabetic groups than in the healthy groups, but insignificantly (P ≤ 0.05). The brain α-Syn level significantly increased in the EDT group compared to the T group (P ≤ 0.05). The serum level of α-Syn in the ED group was significantly higher than in the E and D groups (P ≤ 0.05). The brain HSF1 level was significantly higher in the ED group compared to the D group (P ≤ 0.05). The gene expression of hsf1 was significantly reduced in the E group compared to the other groups and the EDT group compared to ED and CDT groups (P ≤ 0.05). Furthermore, the serum HSF1 level significantly increased in the ED group compared to the D group (P ≤ 0.05). ConclusionThe results of this study suggest that progressive endurance running may improve neuroprotective conditions in diabetic patients by increasing HSF1 in the brain.

Systematic assessment of streptozotocin-induced diabetic metabolic alterations in rats using metabolomics.

Type 1 diabetes is characterized by elevated blood glucose levels, which negatively impacts multiple organs and tissues throughout the body, and its prevalence is on the rise. Prior reports primarily investigated the serum and urine specimen from diabetic patients. However, only a few studies examined the overall metabolic profile of diabetic animals or patients. The current systemic investigation will benefit the knowledge of STZ-based type 1 diabetes pathogenesis. Male SD rats were arbitrarily separated into control and streptozotocin (STZ)-treated diabetic rats (n = 7). The experimental rats received 50mg/kg STZ intraperitoneal injection daily for 2 consecutive days. Following 6 weeks, metabolites were assessed via gas chromatography-mass spectrometry (GC-MS), and multivariate analysis was employed to screen for differentially expressed (DE) metabolites between the induced diabetic and normal rats. We identified 18, 30, 6, 24, 34, 27, 27 and 12 DE metabolites in the serum, heart, liver, kidney, cortex, renal lipid, hippocampus, and brown fat tissues of STZ-treated diabetic rats, compared to control rats. Based on our analysis, the largest differences were observed in the amino acids (AAs), B-group vitamin, and purine profiles. Using the metabolic pathway analysis, we screened 13 metabolic pathways related to the STZ-exposed diabetes pathogenesis. These pathways were primarily AA metabolism, followed by organic acids, sugars, and lipid metabolism. Based on our GC-MS analysis, we identified potential metabolic alterations within the STZ-exposed diabetic rats, which may aid in the understanding of diabetes pathogenesis.

The Effect of Chilgoza Pine Nut (Pinus gerardiana Wall.) on Blood Glucose and Oxidative Stress in Diabetic Rat

Purpose: Diabetes can increase oxidative stress in various tissues of the body, and the progress of this process is associated with intensification of the complications of diabetes. The current study purposed to evaluate the protective effect of Pinus gerardiana (PG) seed on oxidative stress induced by diabetes in the liver and serum of streptozotocin (STZ)- induced diabetic rats. Materials and Methods: This interventional study was performed on 36 male Wistar rats. The rats were randomly divided into 6 groups (healthy controls, healthy treated with 3% and 6% (PG), diabetic control, diabetic treated with 3% and 6% (PG) doses). After 6 weeks of intervention, weight, glucose, and oxidative stress parameters in serum and liver including total antioxidant capacity, malondialdehyde, total thiol and superoxide dismutase activity were measured. Data analysis was done by statistical software version 16 and Tukey’s one-way ANOVA tests. Results: Diabetic rats showed significantly higher malondialdehyde and fasting glucose levels (12±1.2 mmol/L) and significant reductions in fasting insulin serum, weight (−37%), and activity of superoxide dismutase enzymes, total thiol groups, and total antioxidant capacity of serum and liver (about +49% in liver and +16% in serum) (p &lt; 0.001) compared with the healthy groups. Oral administration of PG nuts to diabetic rats caused a significant reduction in malondialdehyde and fasting glucose levels (−43%) and weight loss (+15%), and a significant increase in activity of superoxide dismutase enzymes, total thiol groups, and total antioxidant capacity of serum and liver (p &lt; 0.001). Conclusion: The present study concluded that PG can decrease fasting blood glucose, improve insulin resistance, reduce weight loss, and improve oxidative stress indices in the serum and liver of STZ-induced diabetic rats. It is a potential therapeutic food supplement for the treatment and prevention of hyperglycemia and high oxidative stress of diabetes.

Alleviative effects of α-lipoic acid on muscle atrophy via the modulation of TNF-α/JNK and PI3K/AKT pathways in high-fat diet and streptozotocin-induced type 2 diabetic rats.

Diabetes mellitus (DM) is often accompanied by clinical complications such as sarcopenia. Previous studies have indicated that oxidative stress and insulin resistance (IR) are highly associated with the pathogenesis of diabetic myopathy. α-lipoic acid (ALA), a potent biological antioxidant, exists abundantly in a variety of plants and vegetables. This study aimed to investigate the ameliorative effect of ALA on muscle atrophy in type 2 diabetic rats induced by high-fat diet feeding (HFD) plus streptozotocin (STZ) injection. The HFD/STZ-induced diabetic rats were orally administered 50, 100, or 200 mg/kg body weight ALA once a day for 13 weeks. The results showed that ALA at the tested concentrations significantly increased the soleus muscle mass and muscle fibers in diabetic rats. Proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, were found to decrease in both the serum and muscle of ALA-treated diabetic rats. ALA significantly reduced the protein-expression levels of phosphorylated c-Jun N-terminal kinase (pJNK)/JNK, forkhead box O3 (FOXO3), and muscle ring-finger protein-1 (Murf1); whereas, it enhanced the protein-expression levels of phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (pAKT)/AKT, myogenin determination gene D (MyoD), the mechanistic target of rapamycin (mTOR), and myosin heavy chain (MyHC) in the soleus muscle of diabetic rats. The results from this study suggested that ALA treatment may preserve soleus muscle mass, alleviate muscle atrophy by suppressing the TNF-α/JNK pathway, and ameliorate the PI3K/AKT pathway in HFD/STZ-induced type 2 diabetic rats.

Chlorogenic acid attenuates pro-inflammatory response in the blood of streptozotocin-induced diabetic rats

BackgroundChlorogenic acid (CGA) has been shown to reduce pro-inflammation by scavenging reactive oxygen species (ROS) and reactive nitrogen species. In this study, the anti-inflammatory effect of CGA was expanded to streptozotocin (STZ)-induced diabetic rats. The inter-relationships among oxidative stress, pro-inflammation, and cytochrome P450 (CYP) 1A enzymes were also investigated in peripheral blood mononuclear cells (PBMC) of STZ-diabetic rats.ResultsThe levels of pro-inflammatory cytokines, interleukin-6 and tumor necrosis factor-alpha, increased by approximately 3.4- and 2.9-fold, respectively, and the albumin concentration decreased in the serum of STZ-induced diabetic rats compared to normal rats. The C-reactive protein (CRP) values also increased by about 3.8-fold higher, indicating that STZ induced an inflammation in the blood of STZ-diabetic rats. The expression levels and catalytic activities of CYP1A enzymes were elevated by approximately 2.2–2.5- and 4.3–6.7-fold, respectively, in the PBMC of STZ-treated rats. A decrease in the amount of PBMC-bound albumin was also observed. In contrast, the levels of cytokines and CRP in serum and the activities of CYP1A enzymes in PBMC were significantly reduced in CGA-treated diabetic rats in a CGA concentration-dependent manner. In addition, STZ-mediated elevation of ROS in serum and PBMC was decreased by the CGA administration. However, the CGA treatment did not change the enhanced blood glucose level and expression of CYP1A enzymes by STZ. STZ-mediated decrease in the levels of serum and PBMC-bound albumin was not also restored by the CGA administration.ConclusionsThese results suggest that CGA could be used to treat type 1 diabetes-induced inflammation.

Cinnamic acid is beneficial to diabetic cardiomyopathy via its cardioprotective, anti-inflammatory, anti-dyslipidemia, and antidiabetic properties.

Diabetes-related health issues are increasing day by day in public,and diabetic cardiomyopathy (DCM) is one serious issue among them. There is a lack of proper strategy to control and manage DCM. Here we are attempting a nutraceutical-based approach to protect the heart from DCM. The beneficial effect of cinnamic acid (CiA), was evaluated in an experimental model of diabetes. For this, diabetic model was created by feeding male Wistar rats with a high fat, high fructose diet for 6 months and a single dose of streptozotocin (25 mg/kg bwt). Metformin was used asthe positive control. The diabetic rats showed insulin resistance, myocardial injury, and a significant increase of total cholesterol, triglycerides, and LDL. Development of DCM was evident from the increased cardiac mass index, LDH, CKMB, ANP, and CRP levels in the diabetic group. There was a significant increase in the levels of cardiac hypertrophy markers like TGF-β and β-MHC in the hearts of diabetic rats revealing DCM. Pro-inflammatory cytokines (TNF-α, IL-6) and lipid peroxides were significantly elevated in the serum of diabetic rats. Histopathology revealed inflammation and necrosis in the heart of diabetic rats confirming DCM. Oral administration of CiA (5 and 10 mg/kg bwt) prevented the development of DCM via its cardioprotective, anti-inflammatory, anti-dyslipidemia potential, and antidiabetic properties. Similarly, metformin (50 mg/kg bwt) has also shown protection against DCM. We conclude from this study that CiA is found to be beneficial against DCM and recommend more detailed preclinical and clinical studies to develop CiA-based nutraceutical against DCM.

The protective effect of &lt;em&gt;Matricaria pubescens&lt;/em&gt; extracts against alloxan-induced hyperglycemia in rats

This study aims to investigate the plausible inhibitory capacity of Matricaria pubescens methanolic extract (EMMP) on key diabetes-related enzymes in diabetic rats. A significant increase in the serum and pancreatic α-amylase activity in untreated diabetic rats (Diab) by 61% and 75% respectively produced a remarkable rise in blood glucose levels of 184% compared with the controls. However, the treatment of diabetic rats with the extract (Diab + EMMP) caused a significant decrease in pancreatic α-amylase activity in the pancreas (15%) and in serum (28%) compared to untreated diabetic rats. Therefore, a considerable reduction in blood sugar level has been observed reaching 28%. A significant decrease was observed in the glycated hemoglobin (HbA1c) level (28%) in rats treated with EMMP compared to untreated diabetics. Furthermore a significant increase in the pancreatic serum lipase activity (59%) compared to the control group, led to a distinguished inhibition (21%) in diabetic rats treated with EMMP. A potent protective action of β-cells was observed in diabetic rats treated with EMMP. However, we observed recovery in body weight in the diabetic rats treated with EMMP.

Explore the Active Ingredients and Mechanisms in Musa basjoo Pseudostem Juice against Diabetes Based on Animal Experiment, Gas Chromatography-mass Spectrometer and Network Pharmacology

Musa basjoo pseudostem juice (MBSJ) is a well-known Chinese medicine, and Miao people use MBSJ to treat diabetes. In this work, the active ingredients and molecular mechanism of MBSJ against diabetes were explored. Anti-diabetic activity of MBSJ was evaluated using diabetic rats, and then the ingredients in the small-polar parts of MBSJ were analyzed by gas chromatography-mass spectrometer (GC-MS). Targets were obtained from several databases to develop the "ingredienttarget- disease" network by Cytoscape. A collaborative analysis was carried out using the tools in Cytoscape and R packages, and molecular docking was also performed. MBSJ improved the oral glucose tolerance and insulin tolerance, and reduced fasting blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride, and low-density lipoprotein levels in the serum of diabetic rats. 13 potential compounds were identified by GC-MS for subsequent analysis, including Dibutyl phthalate, Oleamide, Stigmasterol, Stigmast-4-en-3-one, etc. The anti-diabetic effect of MBSJ was related to multiple signaling pathways, including Neuroactive ligand-receptor interaction, Phospholipase D signaling pathway, Endocrine resistance, Rap1 signaling pathway, EGFR tyrosine kinase inhibitor resistance, etc. Molecular docking at least partially verified the screening results of network pharmacology. MBSJ had good anti-diabetic activity. The small-polar parts of MBSJ were rich in anti-diabetic active ingredients. Furthermore, the analysis results showed that the anti-diabetic effect of the small-polar parts of MBSJ may be the result of multiple components, multiple targets, and multiple pathways. The current research results can provide important support for studying the active ingredients and exploring the underlying mechanism of MBSJ against diabetes.

Modulatory effects of vitamin B3 and its derivative on the levels of apoptotic and vascular regulators and cytoskeletal proteins in diabetic rat brain as signs of neuroprotection

BackgroundBeneficial effects of nicotinamide (NAm) and its derivates have been earlier shown in animal models of diabetes mellitus (DM), but the mechanisms of their neuroprotective activities are still largely unknown. The aim of the present study was to investigate if NAm and conjugate of nicotinic acid with gamma-aminobutyric acid (N-GABA) are able to modulate expression levels of apoptosis regulators, angiogenesis-related molecules, and specific cytoskeletal proteins in diabetic rat brain. MethodsAfter six weeks of streptozotocin induced type 1 DM, rats were daily administered either by NAm (100 mg/kg) or N-GABA (55 mg/kg) intraperitoneally for two weeks. Protein levels were assessed by western blot and immunohistochemistry. ResultsBoth NAm and N-GABA down-regulated NF-κB and Bax levels in diabetic rat brain, suggesting their anti-apoptotic activities. Tested compounds normalized VEGF and nNOS contents improving pro-angiogenic signaling reduced by hyperglycemia. Western blot showed marked up-regulation of astroglial marker GFAP and lowering neurofilament protein levels in DM group, confirmed immunohistochemically, indicating the development of reactive astrogliosis as a major response to diabetes-induced neurodegeneration. NAm had no effects on GFAP and Nf-L levels in the diabetic brain, while N-GABA increased their expression. Inversely, NAm and N-GABA dramatically reduced enhanced levels of GFAP and Nf-L found in the blood serum of diabetic rats, providing for the first time strong evidence for preserving blood-brain barrier integrity by studied compounds. ConclusionThus, NAm and N-GABA may exert neuroprotective effects by decreasing pro-apoptotic regulators levels and improving expression of angiogenic and cytoskeletal proteins impaired by hyperglycemia in rat brain.

Astaxanthin ameliorates hyperglycemia induced inflammation via PI3K/Akt–NF–κB signaling in ARPE-19 cells and diabetic rat retina

Astaxanthin has been reported to possess anti-inflammatory effect but the exact mechanism in protecting the retinal pigment epithelial (RPE) cells is not clear. Hence, we hypothesized that astaxanthin could protect RPE by inhibiting ROS-mediated inflammation. The purpose of this study is to understand the retinal protective mechanism of astaxanthin in modulating hyperglycemia (HG) induced inflammation in ARPE-19 cell and diabetic rat retina. ARPE-19 cells were treated with 30 mM glucose to induce hyperglycemia whereas diabetes was induced in rats with streptozotocin followed by astaxanthin treatment. The level of oxidative stress markers, antioxidant enzyme activity, inflammatory markers (NF-κB, TNF-α, ICAM-1), signaling mediators (PI3K, p-Akt) and nuclear translocation of NF-κB were analyzed in ARPE-19 cells and rat retina. HG-mediated ROS generation and lipid peroxidation were declined upon astaxanthin treatment in ARPE-19 cells. Similarly, astaxanthin treatment found to reduce the elevated levels of nitric oxide, protein carbonyl, and lipid peroxides in diabetic group. Astaxanthin restored the activity of superoxide dismutase, catalase, glutathione peroxidase, and glutathione transferase in serum and retina of diabetic rats. NF-κB, TNF-α, and ICAM-1 levels were higher in HG-treated ARPE-19 cells and diabetic retina compared to control group, whereas astaxanthin treatment lowered their expression. PI3K and p-Akt were higher in high glucose treated ARPE-19 cells and diabetic retina. NAC, LY294002 and PDTC treatment resulted in reduced nuclear translocation of NF-κB and decreased expression of inflammatory markers in HG treated ARPE-19 cells. Thus, we conclude that astaxanthin protected the retinal cells from HG-induced inflammation by modulating NF-κB through ROS-PI3K/Akt signaling cascade.

Anti-osteoporosis effects of Anemarrhenae Rhizoma / Phellodendri Chinensis Cortex herb pair and its major active components in diabetic rats and zebrafish

Ethnopharmacological relevanceAnemarrhenae Rhizoma/Phellodendri Chinensis Cortex (AR/PCC) herb pair has been widely used in traditional Chinese medicines for the treatment of diabetic osteoporosis. However, the anti-diabetic osteoporotic active components of AR/PCC remain unclear. This study aimed to explore the major active ingredients in AR/PCC for its protective effects against bone deterioration induced by diabetes. Materials and methodsThe aqueous extracts of AR/PCC with different proportions (AR:PCC = 1:3, 1:2, 1:1, 2:1 and 3:1, w/w) were prepared. Streptozotocin-induced diabetic rats were orally administrated with the AR/PCC extracts. The absorbed phytochemical compounds in serum of diabetic rats were identified by ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry method and their contents in the AR/PCC extracts were determined by high performance liquid chromatography-ultraviolet detector-evaporative light scattering detector method. The absorbed compounds in the extracts were considered as the major potential active components in AR/PCC, and their combination was defined as M-AR/PCC. A component-knockout approach was applied to evaluate the contribution of each compound in M-AR/PCC. The larvae and adults of diabetic zebrafish models were then used to evaluated the anti-diabetic osteoporotic performance of the M-AR/PCC. The real-time reverse transcription polymerase chain reaction technique was applied to study the regulation effects of M-AR/PCC on osteogenesis and osteoclastgensis in diabetic zebrafish models. ResultsThe phenotypes of diabetic osteoporosis rats induced by streptozotocin were reversed by the oral administration of AR/PCC extracts with different ratios, as evidenced by the increased bone mineral density, bone volume density, trabecular thickness, trabecular number, and decreased trabecular separation of femoral metaphysis. Seven phytochemical compounds were detected in the serum and their contents in AR/PCC varied dramatically with different proportions, including 1 xanthone glycoside and 6 alkaloids. By using diabetic zebrafish larvae model and compound-knockout strategy, each compound in M-AR/PCC were proved to play an indispensable role in the positive regulatory actions in the bone mass of diabetic zebrafish. Furthermore, the herb pair with a ratio of 1:1 and the related M-AR/PCC showed the best therapeutic effects on diabetic osteoporosis. They showed similar performances on the inhibition of the tartrate-resistant acid phosphatase activity and the promotion of the alkaline phosphatase activity in diabetic adult zebrafish model. The M-AR/PCC treatment could decrease the blood glucose, upregulate the mRNA expression levels of osteoblast-related genes (alp, runx2b and opg) and downregulate the expression of osteoclast-related genes (acp5α, rankl and sost) in streptozotocin-induced zebrafish. ConclusionAR/PCC herb pair and its major active components possess potent anti-diabetic osteoporotic effect on streptozotocin-induced in vivo models. The combination of the seven active compounds derived from AR/PCC herbal pair could be a potential agent for protection against osteoporosis associated with diabetes.