Treatment Of Diabetic Rats Research Articles

Using laser-activated antimicrobial therapy with ethanol-solubilized methylene blue for enhancing dental disease treatment in diabetic rats

Using laser-activated antimicrobial therapy with ethanol-solubilized methylene blue for enhancing dental disease treatment in diabetic rats

Renoprotective effect of liraglutide on diabetic nephropathy by modulation of Krüppel-like transcription factor 5 expression in rats.

Diabetic nephropathy (DN) is a serious consequence of diabetes that can develop through the lysophosphatidic acid axis. The purpose of this study was to determine whether the antidiabetic drug liraglutide can slow the development of diabetic kidney damage by altering the lysophosphatidic acid axis via KLF5. Wistar albino rats were divided into nondiabetic and diabetic rats (resulting from an intraperitoneal streptozotocin dose of 30mg/kg and a high-fat diet). These rats were further divided into four groups: nondiabetic control, liraglutide-treated nondiabetic, diabetic control, and liraglutide-treated diabetic. The nondiabetic and diabetic control groups received normal saline for 42 days, while the liraglutide-treated nondiabetic and diabetic groups received normal saline for 21 days, followed by a subcutaneous dose of liraglutide (200 μg/kg/day) for 21 days. Subsequently, serum levels of DN biomarkers were evaluated, and kidney tissues were histologically examined. The protein expression of PCNA, autotaxin, and KLF5 was detected. Liraglutide treatment in diabetic rats decreased DN biomarkers, histological abnormalities in kidney tissues, and the protein expression of PCNA, autotaxin, and KLF5. Liraglutide can slow the progression of DN by modulating KLF5-related lysophosphatidic acid axis. Thus, liraglutide may be an effective treatment for preventing or mitigating diabetes-related kidney damage.

Flavonoid-rich fraction of Monodora tenuifolia Benth seeds improves antioxidant status in male Wistar rats with streptozotocin-induced Diabetes mellitus

BackgroundOxidative stress is a disruption in the balance between free radicals and the body's natural defenses. This study investigated the modulatory effect of a flavonoid-rich fraction of Monodora tenuifolia seed (FRFMTS) on oxidative stress and antioxidant enzymes in diabetic Wistar rats. The plant seeds were collected, and identified then, hydro-ethanolic extract was obtained with 80 % (v/v) ethanol and partitioned with solvents to obtain the FRFMTS. Diabetes mellitus was induced with a single dose of 40 mg/kg bwt streptozotocin and the rats were treated according to their grouping; group 1: non-diabetic control, groups 2 and 3: non-diabetic treated with 25 mg/kg FRFMTS and 50 mg/kg FRFMTS, respectively. Group 4: diabetic control group, groups 5 and 6: diabetic groups treated with 25 mg/kg and 50 mg/kg FRFMTS, respectively, while group 7: diabetic treated with 6.67 mg/kg metformin. Antioxidant status, oxidative stress biomarkers and activities of antioxidant enzymes were determined in plasma, heart, and kidney tissues using established procedures. ResultsPlasma total antioxidant status (TAS) was increased significantly (p < 0.05) in diabetic rats upon treatment with 25 mg/kg FRFMTS (70.4 %), while 50 mg/kg FRFMTS increased TAS by 70 %. The activities of glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in the plasma, heart, and kidney of diabetic rats significantly decreased (61.3 %, 58.8 % and 31.4 % respectively) while lipid peroxidation (LPO) was elevated when compared with normal control groups. Flavonoid-rich fraction of M. tenuifolia at 25 mg/kg bwt and 50 mg/kg bwt significantly increased the activity GPx enzyme by 32.3 % and 72 % in plasma, while there was no significant differences in both kidney and heart of diabetic rats when compared with diabetic control groups. The treatment of diabetic rats with 25 mg/kg FRFMTS and 50 mg/kg FRFMTS improved SOD activity in the plasma (51.5 % and 69.8 %), heart (32.3 % and 27.6 %) and kidney (31.4 % and 27.1 %) respectively, and CAT activity in plasma (44.2 % and 57 %), heart (28.6 % and 60 %) and kidney (69.6 % and 76.7 %) respectively. The concentration of malondialdehyde (MDA) in lipid peroxidation assay in the heart and kidney of diabetic rats treated with 25 mg/kg FRFMTS and 50 mg/kg FRFMTS reduced significantly by (62.5 % and 71.1 % in heart), while 50 mg/kg FRFMTS significantly reduced MDA in kidney by 43.8 %. ConclusionsThe results showed that FRFMTS reduces oxidative stress and enhances the activities of antioxidant enzymes in STZ-diabetic Wistar rats. As such, FRFMTS could be useful in the management of oxidative stress-mediated diabetic complications.

Chemical Profile and Potential Application of Agri-food Waste Products for Counteracting Diabetes Induced Neuropathy in Rats.

This study aimed to prepare defatted ethanol extract of Abelmoschus esculentus leaves, Morus nigra leaves and Punica granatum peel, to identify the chemical composition of these extracts and to explore their efficacy in counteracting diabetic neuropathy. LC-ESI-MS spectrometry was the hyphenated tool for component identification of these extracts. Behavioral, biochemical, and histopathological investigations were carried out after treatments of diabetic rats. The phenolic contents in the extracts are 16.38, 34.75 and 40.57 mg GAE/g extract regarding A. esculentus leaves, M. nigra leaves and P. granatum peel respectively. Chemodiversity of the phenolic contents was observed from the LC/Mass, where A. esculentus extract contained isoflavonoids and flavanones, M. nigra extract consisted of benzofurans, prenylated flavonoids, stilbenes, and xanthones, and P. granatum extract was rich in ellagitanins, condensed tannins, and anthocyanins. The extracts normalize of blood glucose levels, enhance the explorative behavior of the rats and their response time to thermal pain, restore the oxidant/antioxidant balance, attenuate inflammation, augment brain monoamines levels and modulate MAO-A and Ache enzyme activity. Furthermore, they recovered brain histopathological alterations. Conclusively, this study offers experimental evidence for the neuroprotective impact of studied defatted ethanol extracts against diabetic neuropathy via their hypoglycemic effect, antioxidant activity, and anti-inflammatory potential.

Therapeutic effect of oral insulin-chitosan nanobeads pectin-dextrin shell on streptozotocin-diabetic male albino rats

The current study inspects the therapeutic effects of orally ingested insulin-loaded chitosan nanobeads (INS-CsNBs) with a pectin-dextrin (PD) coating on streptozotocin (STZ)-induced diabetes in Wistar rats. The study also assessed antioxidant effects in pancreatic tissue homogenate, insulin, C-peptide, and inflammatory markers interleukin-1 beta and interleukin-6 (IL-1β and IL-6) in serum. Additionally, histopathological and immunohistochemical examination of insulin granules, oxidative stress, nuclear factor kappa B (NF-κB P65), and sirtuin-1 (SIRT-1) protein detection, as well as gene expression of nuclear factor erythroid 2–related factor 2 (Nrf2), heme oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl2), and Bcl-2-associated X protein (Bax) in pancreatic tissue were investigated. After induction of diabetes with STZ, rats were allocated into 6 groups: the normal control (C), the diabetic control (D), and the diabetic groups treated with INS-CsNBs coated with PD shell (50 IU/kg) (NF), free oral insulin (10 IU/kg) (FO), CsNBs-PD shell (50 IU/kg) (NB), and subcutaneous insulin (10 IU/kg) (Sc). The rats were treated daily for four weeks. Treatment of diabetic rats with INS-CsNBs coated with PD shell resulted in a significant improvement in blood glucose levels, elevated antioxidant activities, decreased NF-κB P65, IL-1β, and IL-6 levels, upregulated Nrf-2 and HO-1, in addition to a marked improvement in the histological architecture and integrity compared to the diabetic group. The effects of oral INS-CsNBs administration were comparable to those of subcutaneous insulin. In conclusion, oral administration of INS-loaded Cs-NBs with a pectin-dextrin shell demonstrated an ameliorative effect on STZ-induced diabetes, avoiding the drawbacks of subcutaneous insulin.

Insights into the Cardioprotective Effects of Pyridoxine Treatment in Diabetic Rats: A Study on Cardiac Oxidative Stress, Cardiometabolic Status, and Cardiovascular Biomarkers.

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.

Hypoglycemic Ability of Sericin-Derived Oligopeptides (SDOs) from Bombyx mori Yellow Silk Cocoons and Their Physiological Effects on Streptozotocin (STZ)-Induced Diabetic Rats.

Patients with diabetes require daily medication to maintain blood sugar levels. Nevertheless, the long-term use of antidiabetics can lose efficacy and cause degeneration in some patients. For long-term diabetes care, integrating natural dietary foods and medicine is being considered. This study investigated the impact of SDOs on blood sugar levels and their physiological effects on diabetic rats. We induced diabetes in male Wistar rats with STZ (50 mg/kg) and then administered an oral glucose tolerance test to determine the SDO dosage comparable to glibenclamide. The rats were divided into nine groups: normal, diabetic, and diabetic with insulin (10 U/kg), glibenclamide (0.6 mg/kg), bovine serum albumin (BSA; 200 mg/kg), soy protein isolate (200 mg/kg), or SDOs (50, 100, and 200 mg/kg). Diabetic rats administered SDOs had a higher body weight and serum insulin but a lower blood sugar than diabetic control rats. Biochemical assays indicated lower AST/SGOT, ALT/SGPT, BUN, and triglycerides but higher HDL in the SDO groups. Immunohistochemistry showed that SDOs reduced damaged islet cells, increased beta-cell size, and improved insulin levels while decreasing alpha cell size and glucagon. The vascular effects of SDOs were like those of normal control treatment and insulin treatment in diabetic rats. SDOs, a yellow silk protein, show potential for long-term diabetes care.

Hepatoprotective Effects of Curcumin on Liver Injury in Streptozocin-induced Diabetic Rats

Introduction: Type 2 diabetes mellitus is characterized by chronically elevated blood sugar levels associated with disruption of the inflammatory and oxidative state and dyslipidemia. Curcumin is a highly pleiotropic molecule with hypoglycemic, hypolipidemic, anti-inflammatory, and antioxidant properties. The aim of this study was to evaluate the effects of curcumin on the liver of streptozotocin-induced diabetic rats. Materials and Methods: Thirty-two adult male rats were used in the study. The rats were divided into four groups: Control (C), Diabetes (D), Curcumin (CUR), and Diabetes + Curcumin (D + CUR) (n = 8). The groups given curcumin were given 60 mg/kg curcumin by gavage once a day during the 14-day study period. At the end of the experiment, biochemical, stereological, histological, and immunohistochemical analyses were performed on blood and liver samples taken from rats sacrificed. Results: After curcumin treatment in diabetic rats, there was a significant decrease in blood glucose levels, hepatic markers, and levels of thiobarbituric acid reactive substances (P &lt; 0.01). Furthermore, a significant increase in enzymatic antioxidants such as superoxide dismutase, catalase, and glutathione peroxidase was observed after treatment (P &lt; 0.01). It was determined that curcumin decreased the apoptotic index and the number of dual-nucleated hepatocytes in the liver, and provided support for liver regeneration (P &lt; 0.01). Discussion and Conclusion: Based on the findings of this study, it can be concluded that curcumin has the potential to protect against hyperglycemia-induced oxidative stress and apoptosis in liver cells, and also induces regeneration in damaged liver.

Sodium tungstate (NaW) decreases inflammation and renal fibrosis in diabetic nephropathy

BackgroundDiabetic Nephropathy is one of the most severe complications of Diabetes Mellitus and the main cause of end-stage kidney disease worldwide. Despite the therapies available to control blood glucose and blood pressure, many patients continue to suffer from progressive kidney damage. Chronic hyperglycemia is the main driver of changes observed in diabetes; however, it was recently discovered that inflammation and oxidative stress contribute to the development and progression of kidney damage. Therefore, it is important to search for new pharmacological therapies that stop the progression of DN. Sodium tungstate (NaW) is an effective short and long-term antidiabetic agent in both type 1 and type 2 diabetes models. MethodsIn this study, the effect of NaW on proinflammatory signalling pathways, proinflammatory proteins and fibrosis in the streptozotocin (STZ)-induced type 1 diabetic rat model was analysed using histological analysis, western blotting and immunohistochemistry. ResultsNaW treatment in diabetic rats normalize parameters such as glycemia, glucosuria, albuminuria/creatinuria, glomerular damage, and tubulointerstitial damage. NaW decreased the proinflammatory signaling pathway NF-κB, inflammatory markers (ICAM-1, MCP-1 and OPN), profibrotic pathways (TGFβ1/Smad2/3), reduced epithelial-mesenchymal transition (α -SMA), and decreased renal fibrosis (type IV collagen). ConclusionNaW could be an effective drug therapy for treating human diabetic nephropathy.

Rosa canina extract relieves methylation alterations of pancreatic genes in STZ-induced diabetic rats : Gene methylation in diabetic rats treated with an extract.

Diabetes is a chronic metabolic disease that affects many parts of the body. Considering diabetes as a beta cells' defect and loss, the focus is on finding mechanisms and compounds involved in stimulating the function and regeneration of pancreatic β-cells. DNA methylation as an epigenetic mechanism plays a pivotal role in the β-cells' function and development. Considering the regenerative and anti-diabetic effects of Rosa canina extract, this study aimed to assess the methylation levels of Pdx-1, Pax-4, and Ins-1 genes in diabetic rats treated with Rosa Canina extract. Streptozotocin-induced diabetic rats were used to evaluate the frequency of Pdx-1, Pax-4, and Ins-1 gene methylation. Treatment groups were exposed to Rosa canina as spray-dried and decoction extracts. Following blood glucose measurement, pancreatic DNA was extracted and bisulfited. Genes' methylation was measured using MSP-PCR and qRT-PCR techniques. Oral administration of Rosa canina extracts significantly reduced blood sugar levels in diabetic rats compared to the control group. The methylation levels of the Pdx-1, Pax-4, and Ins-1 genes promoter in streptozotocin-induced diabetic rats increased compared to the control rats while, the treatment of diabetic rats with Rosa canina extracts, spray-dried samples especially, led to a decreased methylation in these genes. The results of this study showed that Rosa canina extract as a spray-dried sample could be effective in treating diabetes by regulating the methylation of genes including Pdx-1, Pax-4, and Ins-1 involved in the activity and regeneration of pancreatic islet cells.

Near-infrared light activated rapidly separable polymeric microneedles for transdermal biologics delivery

Polymeric microneedles (PMNs) are an attractive transdermal drug delivery approach with minimal invasiveness and improved patient compliance. However, it is uncomfortable and inconvenient for patients to wear a PMN patch for hours or days until complete payload release. Here, we report a facile strategy to fabricate rapidly separable PMN arrays activated by near-infrared (NIR) light (NIR-RS-PMN) with enhanced mechanical strength through introduction of a photothermal-sensitive spacer integrating plasmonic gold nanorods into a biocompatible sodium hyaluronate matrix. Under NIR irradiation, the NIR-RS-PMN achieved rapid separation of the patch backing and microneedles within 1 min. The loaded bioactive therapeutics, e.g., insulin and RNA, were well-preserved during fabrication, NIR irradiation, and 20-day storage at room temperature. The NIR-RS-PMN was well tolerated by rats without skin irritation. Its feasibility for biologics delivery was further established by the treatment of diabetic rats with insulin encapsulated PMNs. The innovative PMNs increase ease of use and achieve effective and precise payload delivery, which may increase access to biopharmaceuticals and vaccines in remote and resource-limited communities.

Garlic oil improves small intestinal motility in experimentally induced type II diabetes mellitus in female Wistar rats.

Diabetes mellitus adversely affects the contractile ability of the small intestine. However, there is a paucity of studies investigating the impact of garlic oil on small intestinal motility. This study aimed to evaluate the potential beneficial effects of garlic oil on type 2 diabetes mellitus in rats. Thirty-six adult female Wistar rats (n = 36) were divided into four groups: control, non-diabetic rats supplemented with garlic oil, diabetic rats, and diabetic rats treated with garlic oil. The rats were anesthetized using pentobarbitone (40 mg/kg BW); various motility parameters and oxidative markers were determined in small intestinal segments. Measurements were taken for naso-anal length, waist circumference, fasting blood glucose level (FBG), and plasma insulin level. Compared to the control group, the diabetic rats exhibited a reduction in the average force of contraction and motility index in all small intestinal segments. Furthermore, the rats exhibited a reduction in the average duration of muscle contraction only in the jejunum. The rats also exhibited hyperglycemia, insulin resistance, significant oxidative stress, and obesity. This was proven by changes in motility parameters, fasting blood glucose levels, HOMA-IR values, intestinal MDA levels, and waist circumference. The non-diabetic rats supplemented with garlic oil also exhibited a decrease in the average force of contraction and motility index in all small intestinal segments, despite having consistently higher Lee index and waist circumference values. However, the diabetic rats treated with garlic oil demonstrated improved small intestinal motility in nearly all small intestinal segments and a reduction in oxidative stress. In conclusion, rats with diabetes mellitus experienced a decrease in small intestinal motility, which is primarily driven by oxidative stress. Normal rats administered with garlic oil supplements exhibited similar effects. In contrast, garlic oil treatment in diabetic rats led to enhanced small intestinal motility and a notable anti-hyperglycemic effect, which can be attributed to the potent antioxidant properties of garlic oil.

Chrysophyllum albidum (African star apple) Fruit-Skin Attenuates Hyperglycemia-Mediated Oxidative Stress in Experimental Diabetic Rats

Diabetes mellitus, a chronic metabolic disturbance characterized by hyperglycemia has become a health problem affecting millions of people worldwide. Hyperglycemia mediated oxidative stress performs a key role in diabetic complications. The fruit-skin of Chrysophyllum albidum (African star apple) has been reported to have anti-hyperglycemic, hypolipidemic and in vitro antioxidant properties, but its effect on oxidative damage in diabetic animals has not been well investigated. This study investigated the effect of Chrysophyllum albidum fruit-skin (CAFS) in mitigating hyperglycemia induced oxidative stress in diabetic rats. Oxidative stress markers included superoxide dismutase (SOD) and catalase (CAT), lipidperoxidation status using malondialdehyde and non-enzymatic antioxidants in serum, hepatic and pancreatic tissues. Non-diabetic and streptozotocin-diabetic rats were compared after 4 weeks of treatment. The diabetic untreated group showed significant (p&lt; 0.05) elevation of malondialdehyde and depression of non-enzymatic antioxidants levels, while suppressing SOD and CAT activities in serum, hepatic and pancreatic tissues when compared to normal rats. CAFS supplemented diet treatment ameliorated these metabolic disturbances and increased the activities of hepatic and pancreatic SOD from 0.28±0.25 to 0.61±0.13 Unit/mg protein and 0.08±0.01 to 0.15±0.01 Unit/mg protein respectively and CAT from 0.21±0.06 to 0.81±0.17 Unit/mg protein and 0.07±0.01 to 0.50±0.15 Unit/mg protein respectively. The findings suggest that CAFS treatment in diabetic rats exerts a protective effect via attenuation of oxidative stress mediated by hyperglycemia and improves the antioxidant status.&#x0D;

Phytic acid promotes high glucose-mediated bone marrow mesenchymal stem cells osteogenesis via modulating circEIF4B that sponges miR-186-5p and complexes with IGF2BP3

Diabetes-related hyperglycemia inhibits bone marrow mesenchymal stem cell (BMSC) function, thereby disrupting osteoblast capacity and bone regeneration. Dietary supplementation with phytic acid (PA), a natural inositol phosphate, has shown promise in preventing osteoporosis and diabetes-related complications. Emerging evidence has suggested that circular (circ)RNAs implicate in the regulation of bone diseases, but their specific regulatory roles in BMSC osteogenesis in hyperglycemic environments remain elucidated. In this study, in virto experiments demonstrated that PA treatment effectively improved the osteogenic capability of high glucose-mediated BMSCs. Differentially expressed circRNAs in PA-induced BMSCs were identified using circRNA microarray analysis. Here, our findings highlight an upregulation of circEIF4B expression in BMSCs stimulated with PA under a high-glucose microenvironment. Further investigations demonstrated that circEIF4B overexpression promoted high glucose-mediated BMSC osteogenesis. In contrast, circEIF4B knockdown exerted the opposite effect. Mechanistically, circEIF4B sequestered microRNA miR-186-5p and triggered osteogenesis enhancement in BMSCs by targeting FOXO1 directly. Furthermore, circEIF4B inhibited the ubiquitin-mediated degradation of IGF2BP3, thereby stabilizing ITGA5 mRNA and promoting BMSC osteogenic differentiation. In vivo experiments, circEIF4B inhibition attenuated the effectiveness of PA treatment in diabetic rats with cranial defects. Collectively, our study identifies PA as a novel positive regulator of BMSC osteogenic differentiation through the circEIF4B/miR-186-5p/FOXO1 and circEIF4B/IGF2BP3/ITGA5 axes, which offers a new strategy for treating high glucose-mediatedBMSCosteogenic dysfunction and delayed bone regeneration in diabetes.

Tempol a superoxide dismutase mimic reduces cardiac muscle cell death through the control of oxidative stress in streptozotocin-induced diabetes

ABSTRACT Diabetes mellitus (DM) a metabolic disorder resulting in myocardial injury and diabetic cardiomyopathy (DCM) in association with oxidative stress induction. This study was therefore, investigated the potential protective effect of Tempol (TPL) on oxidative cardiac damage in experimental diabetic rats. Rats were assigned to three equal groups: group (NC); normal control rats received citrate buffer injections. Group (DC): diabetic control rats received a single i.p. STZ injection (60 mg/kg body weight), and Group (D/TPL) diabetic rats treated with TPL (10 mg/kg b.w; by i.p. injection) for four weeks. Our results showed a significant increment in plasma creatine phosphokinase (CPK), lactate dehydrogenase (LDH) activities, cholesterol, triglycerides, Nitric oxide (NO), and lipid peroxidation (LPO), In addition, GSH content and antioxidant enzyme activity were significantly deceased in DC group compared to normal control. While TPL treatment significantly ameliorated the observed biochemical abnormalities. Further, TPL reduced number of dead myocardial cells in diabetic-treated rats and, remarkably improved the histopathological alterations of the aorta. The results proved the protective effect of tempol on STZ-induced diabetic cardiomyopathy by reducing myocardial cell death through reducing oxidative stress and inhibition of lipid peroxidation.

Identification of isobenzofuranone derivatives as promising antidiabetic agents: Synthesis, in vitro and in vivo inhibition of α-glucosidase and α-amylase, computational docking analysis and molecular dynamics simulations

Diabetes mellitus, one of the major health challenges of the 21st century, is associated with numerous biomedical complications including retinopathy, neuropathy, nephropathy, cardiovascular diseases and liver disorders. To control the chronic hyperglycemic condition, the development of potential inhibitors of drug targets such as α-glucosidase and α-amylase remains a promising strategy and focus of continuous efforts. Therefore, in the present work, a concise library of isobenzofuranone derivatives (3a-q) was designed and synthesized using Suzuki-Miyaura cross-coupling approach. The biological potential of these heterocyclic compounds against carbohydrate-hydrolyzing enzymes; α-glucosidase and α-amylase, was examined. In vitro inhibitory results demonstrated that the tested isobenzofuranones were considerably more effective and potent inhibitors than the standard drug, acarbose. Compound 3d having an IC50 value of 6.82 ± 0.02 μM was emerged as the lead candidate against α-glucosidase with ⁓127-folds strong inhibition than acarbose. Similarly, compound 3g demonstrated ⁓11-folds higher inhibition strength against α-amylase when compared with acarbose. Both compounds were tested in vivo and results demonstrate that the treatment of diabetic rats with α-amylase inhibitor show more pronounced histopathological normalization in kidney and liver than with α-glucosidase inhibitor. The Lineweaver-Burk plot revealed an uncompetitive mode of inhibition for 3d against α-glucosidase whereas compound 3g exhibited mixed inhibition against α-amylase. Furthermore, in silico molecular docking and dynamics simulations validated the in vitro data for these compounds whereas pharmacokinetics profile revealed the druglike properties of potent inhibitors.

Antioxidant Effect of Ethanol Extract of C. sativus on Streptozotocin-Induced Diabetic Rat Liver

The present study investigated the antioxidant effect of ethanol extract of Cucumis sativus on streptozotocin (STZ)-induced diabetic rat liver. Adult male Wistar albino rats (n = 25, mean weight = 215 ± 15 g) were randomly assigned to five groups of 5 rats each: normal control, diabetic control, metformin, 200 mg/kg body weight (bwt) extract and 300 mg/kg bwt extract groups. Diabetes mellitus was induced in the rats via intraperitoneal injection of 50 mg/kg bwt STZ. The diabetic rats were then treated for 21 days with either metformin (50 mg/kg bwt) or the extract at doses of 200 and 300 mg/kg bwt, respectively. Activities of antioxidant enzymes such as catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) as well as antioxidant molecules like retinoic acid, ascorbic acid and α-tocopherol were evaluated in liver homogenate. The results showed that induction of diabetes mellitus with STZ significantly increased the fasting blood glucose (FBG) concentrations of the rats (p &lt; 0.05). However, treatment of the diabetic rats with the extract markedly reduced the FBG concentration and body weights of rats (p &lt; 0.05). Treatment of diabetic Wistar rats with ethanol extract of C. sativus significantly increased activities of the antioxidant enzymes and molecules as well as concentrations of nitric oxide (NO), but it markedly reduced the concentrations of hepatic total protein (TP) and malondialdehyde (MDA) (p &lt; 0.05). These results suggest that ethanol extract of the medicinal plant can enhance antioxidant defense in the liver of STZ-induced diabetic rats.

Antiarrhythmic potentials of irisin in ischemia/reperfusion injury of diabetic rats through modulating mitochondria-endoplasmic reticulum interaction and inhibiting pyroptosis.

Myocardial arrhythmia is a major complication of ischemia-reperfusion (I/R) injury in patients with diabetes. Irisin has significant cardioprotective effects, while its role in the pathophysiology of I/R injury-induced myocardial arrhythmia in the presence of diabetes is not well identified. Here, we aimed to investigate the potential antiarrhythmic impacts and mechanisms (mitochondrial biogenesis, endoplasmic reticulum (ER) stress, and pyroptosis) by which irisin reduces I/R injury-induced myocardial arrhythmia in diabetic rats. Thirty high-fat diet-induced diabetic rats were subjected to I/R injury and myocardial arrhythmia. Irisin (0.5 μg/kg/day) was injected intraperitoneally before induction of I/R injury. Electrocardiography was used to measure the incidence and severity of ventricular arrhythmias. ELISA and western blotting analyses were employed to quantify the expression of mitochondrial biogenesis, ER stress, and pyroptosis-related proteins in ischemic myocardium. Irisin treatment in diabetic rats significantly decreased the lactate dehydrogenase level and the number and severity of arrhythmia induced by I/R injury. Irisin up-regulated the expression of mitochondrial biogenesis-related proteins while down-regulating the expression of ER stress and pyroptosis-related proteins. Furthermore, the inhibition of mitochondrial quality control by mdivi-1 significantly abolished the cardioprotective effect of irisin. Our findings suggest that irisin reduced myocardial arrhythmia induced by I/R injury in diabetic rats by modulating the interaction of mitochondrial biogenesis and ER stress proteins and inhibiting the pyroptosis pathway. These findings provide a promising strategy for managing myocardial arrhythmia in diabetic patients, but supplementary studies are needed to confirm the clinical efficacy of irisin in these patients.

Evaluation of the Antidiabetic Activity of Asphodelus Tenuifolius in Normal and Alloxan-induced Diabetic Rats

Asphodelus tenuifolius is traditionally used for the treatment of diabetes mellitus (DM). The current study aims to investigate the antidiabetic activity of Asphodelus tenuifolius in normal and alloxan-induced diabetic rats. Ethanolic and aqueous extracts of whole Asphodelus tenuifolius plant were prepared by using the maceration process. DM was induced by a single intraperitoneal injection of alloxan monohydrate (140 mg/kg b.w) in rats. Glibenclamide was used as the reference drug. In an acute study, ethanolic extract of Asphodelus tenuifolius (ATEE) and aqueous extract of Asphodelus tenuifolius (ATAqE) were administered in 200 and 400 mg/kg doses to normal and alloxan-induced diabetic rats. Both extracts (ATEE and ATAqE) significantly lowered the blood glucose level of both normal and diabetic treated rats in a concentration dependent fashion. However, ATEE produced prominent results at the dose of 400 mg/kg. In a fourteen-day study, ATEE considerably decreased the blood glucose level of alloxanized rats. The results were similar to the reference drug, that is, glibenclamide. In the prolonged study, the effects of ATEE on liver enzymes and hematological parameters of diabetic rats were also studied. Hb level and platelet count was increased in ATEE-treated diabetic rats as compared to diabetic control. However, it did not affect other hematological parameters. ATEE significantly decreased the ALP level as compared to diabetic control. Although, the test extract did not significantly alter the SGOT and SGPT levels. Further, the phytochemical testing of ATEE revealed the presence of alkaloids, flavonoids, tannins, and terpenoids. It was concluded that Asphodeleus tenifolius possesses antidiabetic activity. More comprehensive studies are needed in the future to explicate the mechanism of action and to characterize the phyto-components of this plant.

Antidiabetic Studies of Cnestis ferruginea Ethanolic Root Extract in Wistar Rats

The need to develop new and affordable antidiabetic drugs with minimal side effects is a growing area of research interest. The medicinal plant Cnestis ferruginea DC has diverse pharmacological applications. Its leaves and roots are used for the treatment of diabetes by traditional healers. As a result, the antidiabetic activity of ethanolic extract of C. ferruginea (EECF) roots was evaluated in streptozotocin (STZ)-induced diabetic rats. The influence of EECF (200 and 400 mg/kg bw) was studied for three weeks, with glibenclamide as a positive control. The phytochemical screening of EEFC was also performed. Like glibenclamide, treatment with EECF caused a significant (p &lt; 0.05) reduction in fasting blood glucose (FBG) in diabetic rats. A significant (p &lt; 0.05) alteration in serum lipid profile parameters, kidney and liver function parameters, as well as oxidative stress markers in kidney and liver tissues, was observed in diabetic control rats relative to the normal control ones. But the treatment of diabetic rats with EEFC resulted in significant (p &lt; 0.05) restoration of these parameters to a near-normal level. The phytochemical analysis of EEFC showed the presence of alkaloids, anthraquinones, cardiac glycosides, flavonoids, phlobatannins, saponins and tannins. Thus, the results offer proof to support the traditional use of C. ferruginea roots in the treatment of diabetes. The antidiabetic activity of EEFC may be due to its phytoconstituents.