STZ-induced Diabetic Rats Research Articles

Exploring the anti-diabetic potential of Aloe vera: isolation and characterization of bioactive compounds

We investigated the anti-diabetic effects of the ethyl acetate fraction of Aloe vera and its isolated compounds using both in vitro and in vivo study models. In vitro tests showed that the ethyl acetate part of A. vera and its separate compounds had better activity blocking α-glucosidase, α-amylase, and α-lipase. The ethyl acetate fraction and its active constituents, barbaloin and gallic acid, significantly (p < 0.01) normalised blood glucose levels and serum biochemical parameters compared to those of STZ-induced controls. Both barbaloin and gallic acid exhibited maximum glucose-lowering effects in diabetic rats. Ethyl acetate fraction, barbaloin, and gallic acid also showed a significant increase in serum insulin and restoration of the biochemical and antioxidant status of STZ-induced diabetic rats. Therefore, the ethyl acetate fraction of A. vera, barbaloin, and gallic acid demonstrated remarkable anti-diabetic activity in STZ-induced diabetic rats.

Therapeutic Potential of Curcumin in Diabetic Cardiomyopathy: Modulation of Pyroptosis Pathways.

Cardiac inflammation is a basic pathological process of diabetic cardiomyopathy (DCM). Inflammatory response is closely related to pyroptosis, which is a recently identified programmed cell death type. Curcumin (CUR) is a polyphenol extracted from turmeric and has been reported to be crucial in alleviating pyroptosis in DCM. However, the exact mechanism by which CUR improves pyroptosis remains unclear. Therefore, we aimed to investigate the effect of CUR on pyroptosis in DCM and explore the potential mechanisms. The molecular docking (MOD) analysis was performed using AutoDock Tools to evaluate the binding patterns and affinities between CUR and tripartite motif containing 21 (TRIM21), as well as between TRIM21 and gasdermin D (GSDMD). Subsequently, DCM models were established in Sprague-Dawley (SD) rats (in vivo) by administering streptozotocin (STZ) and feeding them a high-fat diet. In addition, H9C2 cells were cultured in a high glucose and palmitate environment to construct in vitro models of DCM. Rats or cells were treated by CUR directly. Subsequently, body weight (BW), heart weight (HW)/BW ratio, fasting blood glucose level, and lipid metabolism were measured. Pathological changes were analyzed using hematoxylin and eosin (H&E) and Masson staining. Small interfering RNA (si-RNA) was used to knockdown TRIM21 expression, and the pyroptosis protein expression and cellular activity were evaluated in different groups. MOD analysis revealed that CUR had a strong binding affinity with TRIM21, and TRIM21 showed a robust interaction with GSDMD. STZ-induced diabetic SD rats showed metabolic abnormalities, structural changes in the ventricle, and the expression of TRIM21 and pyroptosis markers, including nod-like receptor protein-3 (NLRP3), Caspase-1, and GSDMD, were upregulated. CUR reduced cardiac remodeling and improved cardiac function in vivo. CUR inhibited pyroptosis by regulating TRIM21 through in vivo and in vitro studies. CUR improves DCM by regulating TRIM21 expression to inhibit pyroptosis. Furthermore, this study provides novel approaches and experimental evidence for the research and treatment of DCM and presents new insights into its potential mechanisms.

5-Methyltetrahydrofolate and aqueous extract of Spirulina (Arthrospira) ameliorate diabetes and associated complications in STZ-induced diabetic rats.

The online version contains supplementary material available at 10.1007/s13205-024-04170-9.

Gonadal Histo-morphology and Enhanced Fertility Potential of Curcuma longa in Male STZ-induced Diabetic Rats

Gonadal Histo-morphology and Enhanced Fertility Potential of Curcuma longa in Male STZ-induced Diabetic Rats

Activity of glucose-6-phosphate dehydrogenease and its correlation with inflammatory factors in diabetic retinopathy.

This study aims to explore glucose-6-phosphate dehydrogenase (G6PD) activity in diabetic retinopathy (DR) and its correlation with inflammatory factors, elucidating the regulatory role of G6PD in DR pathology. A total of 151 T2DM patients were divided into three groups: diabetes without retinopathy (DNR, n = 59), non-proliferative retinopathy (NPDR, n = 46) and proliferative retinopathy (PDR, n = 49). Plasma G6PD activity was measured by a Randox G6PD kit and compared between these groups. Then the G6PD activity was correlated with inflammatory cytokines and metabolic parameters in these patients. A STZ-induced diabetic rat model was established, G6PD activity was validated by western blot and immunofluorescence staining in the retina of this model. Plasma G6PD activity decreased in the order of DNR, NPDR and PDR groups (P<0.01). G6PD activity was negatively correlated with IL-6, IL-8, TNF-α, cholesterol, and LDL (r = -0.1625, -0.1808, -0.1865, -0.1747, r = -0.1807, P<0.05). Multiple regression analysis showed TNF-α, IL-6, and LDL were independent related factors for G6PD. Logistic regression analysis showed G6PD, triglyceride, cholesterol, IL-8, TNF-α, and macular edema were influencing factors for T2DM with DR. Western Blot analysis indicated a significant reduction of G6PD expression in the retina, and immunofluorescence staining showed distribution of G6PD especially in the retinal endothelium cell decreased. G6PD may play an important role in DR occurrence and progression, with decreased expression correlating closely with lipid metabolism and inflammatory factors.

Alogliptin attenuates STZ-induced diabetic nephropathy in rats through the modulation of autophagy, apoptosis, and inflammation pathways: Targeting NF-κB and AMPK/mTOR pathway.

Diabetic nephropathy (DN) is a type of microvascular complication that arises from diabetes mellitus and leads to further health issues. Most importantly, the prevalence of DN is steadily rising in developed countries. This research explored the therapeutic benefits of alogliptin, a dipeptidyl peptidase IV (DPP-4) inhibitor, on streptozotocin (STZ)-induced DN and its underlying mechanisms in rats. Ten rats were allocated to group 1, served as the normal group; and received saline. To develop diabetes, thirty rats were administered a single intraperitoneal dose of STZ (45mg/kg). STZ-induced diabetic rats were randomly assigned to three groups: group 2 diabetic control; was given saline, groups 3 and 4 received alogliptin (10mg/kg) and (20mg/kg), respectively. The treatment began 8weeks after diabetes onset and continued for four weeks. Histopathological alterations in the kidney were detected. Serum was collected to measure blood glucose levels (BGL), renal function, and lactate dehydrogenase (LDH). Tissue samples were collected to detect changes in oxidative stress (OS), inflammation, 5' adenosine monophosphate-activated protein kinase (AMPK), and the mammalian target of Rapamycin (mTOR) signaling pathways in addition to apoptotic and autophagy changes. Alogliptin reduced STZ-induced histological changes in the kidney as well as OS, and inflammation. Alogliptin also ameliorated the AMPK/mTOR signaling pathways, enhanced autophagy, and reduced apoptosis. These results demonstrate that alogliptin ameliorates inflammation and OS and consequently modulates the AMPK/mTOR axis along with targeting autophagy and apoptosis, leading to the alleviation of DN.

Expression of PPAR-γ TF by newly synthesized thiazolidine-2,4-diones to manage glycemic control: Insights from in silico, in vitro and experimental pharmacology in wistar rats.

In pursuit of novel antidiabetic agents to combat type II diabetes mellitus, our study focused on identifying pharmacophoric features responsible for PPAR-γ expression, a key regulator of glucose homeostasis and lipid metabolism. This goal was achieved through pharmacophore model generation and screening of rationally designed library of thiazolidine-2,4-dione hybrids (7a-7f). The top hits were synthesized, characterized, and evaluated for their in vitro and in vivo antidiabetic activities. Among these, compounds 7b and 7c emerged as promising candidates, exhibiting significant in vitro inhibitory activity against human pancreatic α-amylase (HPA) and human liver α-glucosidase (HLAG) enzymes, along with enhanced glucose uptake in L6 myotube cell lines. Specifically, compound 7b showed 29.04±1.13µM HPA inhibition, 34.21±1.16µg/mL HLAG inhibition, and 77.12±1.02% glucose uptake, while compound 7c displayed 28.35±1.01µM HPA inhibition, 26.21±1.17µM HLAG inhibition, and 78.54±0.54% glucose uptake. Mechanistic studies revealed a dose-dependent increase in PPAR-γ transcription factor expression, supported by molecular docking that showed favorable interactions with key residues TYR473, SER289, and HIE323. Molecular dynamics simulations confirmed the stability of these interactions, and MM/GBSA binding free energy calculations indicated potential for further optimization. In vivo studies in STZ-induced diabetic Wistar rats demonstrated significant improvements in glucose homeostasis, insulin sensitivity, and lipid metabolism, with a notable decrease in triglycerides and VLDL levels. Compound 7c also showed an improved pharmacokinetic profile with a half-life of 4.01h and an elimination rate constant of 0.325, compared to compound 7b. Both compounds enhanced glycogen content and antioxidant biomarkers, with a high safety profile (LD50 of 500mg/kg). Overall, compound 7c stands out as a promising lead for further development, with compound 7b also showing strong potential, providing valuable insights for future antidiabetic drug development efforts.

Effect of the Anti-inflammatory and Antioxidant Effects of Salvia miltiorrhiza On Diabetic Nephropathy in Induced Diabetic Rats

Abstract Diabetic nephropathy, a severe consequence of diabetes, can culminate in chronic kidney disease and end-stage renal failure. Controlling blood glucose levels, reducing inflammation, and managing oxidative stress are important strategies for preventing, delaying, and managing diabetic nephropathy. This study aimed to investigate the efficacy of Salvia miltiorrhiza extract (SME) in ameliorating renal complications within the context of experimental diabetes-induced by streptozotocin (STZ) administration in rats. The study included 40 out of 50 adult male Sprague-Dawley rats, randomly divided into four groups (n = 10): Group I: the control group administered distilled water orally; Group II: SME group received for 4 weeks oral intake of SME (100 mg/kg) per day; Group III: The STZ group was administered one dose of STZ injected intraperitoneally at a dose of 60 mg/kg; and Group IV: STZ + SME group received single STZ injection followed by SME administration for 4 weeks. Diabetic rats demonstrated significantly elevated blood glucose concentrations compared to the control, partially mitigated by treatment with S. miltiorrhiza extract (SME). STZ-induced diabetic rats showed increased kidney tissue cytokines such as tumor necrosis factor-alpha, interleukins (IL)-1β, and IL-6, which were decreased with SME treatment. Furthermore, STZ-induced diabetic rats displayed a significant elevation of malondialdehyde (MDA) levels and a decrease in the actions of superoxide dismutase (SOD) and glutathione (GSH) within the kidney tissue, indicative of oxidative stress. Treatment with SME decreased MDA and elevated GSH and SOD levels in diabetic rats. SME was found to reduce caspase-3 activity in diabetic rat kidneys, indicating a potential role in preventing kidney cell death. Finally, SME treatment also reduced blood urea nitrogen and creatinine levels, suggesting improved kidney function. In conclusion, SME has anti-inflammatory, antioxidant, and anti-apoptotic properties that show therapeutic potential for diabetic nephropathy prevention and treatment.

Effects of Faradarmani Consciousness Field on Hippocampal Structure/Function and Pancreatic Beta Cells in STZ-Induced Diabetic Rats

Effects of Faradarmani Consciousness Field on Hippocampal Structure/Function and Pancreatic Beta Cells in STZ-Induced Diabetic Rats

Study the role of xanthine oxidase inhibitor, allopurinol in experimentally induced steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease which can lead to cirrhosis and hepatic failure. It is observed in patients with both type 1 and type 2 diabetes mellitus (T1DM, T2DM). Allopurinol, a xanthine oxidase inhibitor that is widely used in clinical practice, has been demonstrated to reduce hepatic oxidative stress and attenuate acute liver injury which may be through activation of antioxidant pathways. This work aimed at investigating the role of Allopurinol (ALP) in attenuation of type 1 diabetes associated with Nonalcoholic fatty liver disease (NAFLD) and exploring the possible molecular mechanism by which ALP attenuates NASH in type 1 diabetes. Forty-five adult male albino rats were included in the study. They were randomly allocated to 3 equal groups: group I (control), Group II (diabetic animals), Group III (diabetic animals with allopurinol treatment). At the end of this experimental study measurements of serum glucose, ALT, AST, cholesterol, triglyceride, serum levels of uric acid, malondialdehyde (MDA), serum superoxide dismutase (SOD) were done. Histological analysis of liver tissue to diagnose steatohepatitis and gene expression of nuclear factor-erythroid-2- related factor-2 (Nrf2) &amp; TNFα were done. Diabetic rates treated with allopurinol (group III) showed decrease in serum levels of ALT, AST, cholesterol, uric acid and MDA compared to diabetic rat group. As regards TNF, gene expression was significantly decreased in group III compared to group II. This study also demonstrated that Nrf2α was significantly increased in group III compared to group II. Allopurinol also, ameliorated the histopathological changes observed in group II. In conclusion, allopurinol treatment increases the Nrf2 gene expression in the liver of STZ-induced diabetic rats and ameliorates steatohepatitis through modulation of TNF-α gene expression. Allopurinol could be a candidate for prevention or treatment of NAFLD.

4-Hexylresorcinol Enhances Glut4 Expression and Glucose Homeostasis via AMPK Activation and Histone H3 Acetylation.

This study investigates the potential of 4-hexylresorcinol (4HR) as a novel antidiabetic agent by assessing its effects on blood glucose levels, Glut4 expression, AMPK phosphorylation, and Histone H3 acetylation (Ac-H3) in the liver. In vitro experiments utilized Huh7 and HepG2 cells treated with varying concentrations of 4HR. Glut4, p-AMPK, and Ac-H3 expression levels were quantified via Western blotting. Additionally, GAPDH activity and glucose uptake were evaluated. In vivo experiments employed streptozotocin (STZ)-induced diabetic rats, with or without 4HR treatment, monitoring blood glucose, body weight, and hepatic levels of Glut4, p-AMPK, and Ac-H3. In vitro, 4HR treatment increased GAPDH activity and glucose uptake. Elevated Glut4, p-AMPK, and Ac-H3 levels were observed 8 h after 4HR administration. Inhibition of p-AMPK using compound C reduced 4HR-mediated Glut4 expression. In STZ-induced diabetic rats, 4HR significantly upregulated Glut4, p-AMPK, and Ac-H3 expression in the liver. Periodic 4HR injections mitigated weight loss and lowered blood glucose levels in STZ-injected animals. Histological analysis revealed increased glycogen storage in hepatocytes of the 4HR-treated group. Overall, 4HR enhanced Glut4 expression through upregulation of AMPK activity and histone H3 acetylation in vitro and in vivo, improving hepatic glucose homeostasis and suggesting potential as a candidate for diabetes treatment.

Agmatine alleviates diabetic-induced hyposalivation in rats: A histological and biochemical study

Diabetic patients commonly experience hyposalivation, which can cause challenges with eating, swallowing, dry mouth, and speaking. It also raises the likelihood of developing periodontal disease. This study aimed to evaluate if agmatine could improve the rate of salivation in rats with hyposalivation induced by streptozotocin (STZ). Five groups of Wistar rats were utilized with 10 animals in each group. They were classified as follows; Negative control group (G1), agmatine (G2) group, and Nicotinamide (NA)-STZ (G3) group; received a single intraperitoneal dose of 65 mg/kg of STZ after NA injection. NA was administered to protect residual β cells and enhance their insulin secretion; NA-STZ + Metformin (G4) Metformin-treated diabetic group; at day 10 diabetic rats received 50mg/kg orally for 28 days, and NA-STZ + Agmatine (G5) at day 10 diabetic rats received a daily intraperitoneal dose of 300 mg/kg Agmatine for 28 days. The salivary flow rate was assessed weekly. Then, the animals were euthanized, both parotid (PG) and submandibular (SMG) salivary glands were dissected, and the following parameters were assessed; salivary glands' histopathology, aquaporin 5 (AQP5), caspase-3, E-cadherin expressions, inflammatory markers and finally, salivary glands' oxidative stress status. Agmatine has alleviated the salivary glands' dysfunction in STZ-induced diabetic rats. It normalized diabetes mellitus-associated salivary glands' abnormalities including histopathological abnormalities, decreased AQP5 and E-cadherin expressions, increased caspase-3 expression, and oxidative stress and inflammatory parameters. Agmatine alleviates diabetes mellitus-associated hyposalivation. It can promote PGs and SMGs function through its histological and AQP5 expression improvements.

Evaluation of Vinca Rosea's Protective Effects on Hepatic Function in Streptozotocin-Induced Diabetic Wistar Albino Rats.

Background Diabetes mellitus, characterized by chronic hyperglycemia, often leads to severe hepatic dysfunction, including increased liver enzyme levels and histopathological changes in the liver. Streptozotocin (STZ)-induced diabetic rat models provide a valuable method for evaluating potential therapeutic agents that target hepatic complications. Vinca rosea, a medicinal plant with known anti-diabetic properties, has been used traditionally for its hepatoprotective effects, although scientific evidence is limited. Objective This study aimed to evaluate the protective effects of Vinca rosea leaf extract on hepatic function, including biochemical and histopathological changes, in STZ-induced diabetic Wistar albino rats. Methods Thirty male Wistar albino rats were randomly divided into five groups: Normal control (NC), diabetic control (DC), low-dose Vinca rosea (LD, 200 mg/kg), high-dose Vinca rosea (HD, 400 mg/kg), and positive control (PC, metformin 100 mg/kg). Diabetes was induced by a single intraperitoneal injection of STZ (100 mg/kg). Vinca rosea treatment was administered daily for 30 days. Blood samples were collected at 15 and 30 days to assess blood glucose and liver function, including serum bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels. Liver tissue was collected for histopathological examination. Data were analyzed using analysis of variance (ANOVA), with p < 0.05 considered statistically significant. Results The DC group showed significantly elevated blood glucose levels (256 ± 19.8 mg/dL at 15 days and 308.5 ± 13.1 mg/dL at 30 days). Vinca rosea treatment significantly reduced blood glucose in a dose-dependent manner, with the HD group showing the greatest improvement (143 ± 12.7 mg/dL at 15 days and 158.5 ± 10.7 mg/dL at 30 days). Liver function markers, including total and direct bilirubin, AST, and ALT, were significantly elevated in the DC group, indicating hepatic damage. Vinca rosea-treated groups showed significant improvements in all liver function parameters, with the HD group displaying the most substantial reductions in bilirubin, AST, and ALT levels. Histopathological analysis revealed marked hepatocellular damage in the DC group, including necrosis and ballooning degeneration. In contrast, Vinca rosea-treated groups, particularly the HD group, exhibited near-normal liver architecture with minimal damage. Conclusion Vinca rosea demonstrated significant hepatoprotective effects in STZ-induced diabetic rats by reducing blood glucose levels and improving liver function. These results suggest that Vinca rosea could be a promising therapeutic agent for managing diabetes-related hepatic dysfunction.

Bay 11-7082 mitigates oxidative stress and mitochondrial dysfunction via NLRP3 inhibition in experimental diabetic neuropathy

ObjectiveDiabetic neuropathy is associated with mitochondrial dysfunction and neuroinflammation. Chronic hyperglycemia triggers inflammatory responses and oxidative stress, causing peripheral neuropathy, whereas mitochondrial dysfunction caused by increased ROS generation and reduced bioenergetics maintains the inflammatory cycle. The purpose of this study is to evaluate the pharmacological efficacy of Bay 11–7082 (B11) against diabetic neuropathy in rats. MethodsB11 was administered at doses of 1 and 3 mg/kg to STZ-induced diabetic animals (55 mg/kg, i.p). Behavioral and functional assessments were conducted to assess neuropathy. Molecular protein expressions were evaluated for B11's efficacy against STZ-induced diabetic neuropathic rats and in SHSY5Y cells exposed to 175 mM of d-glucose. ResultsDiabetic rats exhibited deficits in nerve functions, altered nociceptive parameters, and increased expression of NLRP3, ASC, Caspase-1, and NF-κB. Additionally, diabetic animals showed reduced levels of PGC1α/Nrf2/HO-1, with an overexpression of PARP1. Compromised mitochondrial function was evident through increased mitochondrial dynamic marker DRP1 and elevated levels of inflammatory cytokines TNF-α, IL-1β, IL-18, and IL-6. However, B11 administration significantly ameliorated these changes, suggesting that B11's NLRP3 inhibition may be attributed to the activation of the mitochondrial biogenesis pathway via PGC1α/Nrf2/HO-1, along with improved mitochondrial health. In high glucose exposed SHSY5Y cells, B11 treatment attenuated neuroinflammation by inhibiting NLRP3 activation and reducing mitochondrial damage. ConclusionB11, showed a protective effect against diabetic neuropathy by inhibiting oxidative stress, NLRP3 activation, and improving mitochondrial health in experimental diabetic neuropathy. This study provides new mechanistic insights into the neuroprotective role of Bay 11–7082 against diabetic neuropathy.

Effects of Apelin-13 on auditory system in STZ-induced diabetic rats

AimDamage to the auditory pathways is one of the complications of diabetes. The aim of this study was to investigate the potential therapeutic effects of apelin-13 in the auditory pathways of rats with experimentally induced diabetes by examining its effect on auditory brainstem responses, cochlear oxidative stress and inflammatory cytokines. MethodsThirty-two male Wistar albino rats were divided into four groups: sham control, diabetes, apelin and diabetes + apelin. A single dose of 45 mg/kg streptozotocin (STZ) was administered to induce diabetes. The apelin group received 50 µg/kg apelin-13 for seven days intraperitoneally (ip). At the end of the apelin and STZ applications auditory brainstem responses (ABR) was recorded. At the end of the experiment, cochlea was removed and biochemical analyzes were performed. ResultsIn ABR recordings, the latencies of wave V in diabetic group were observed to be longer than those of the control, with the apelin treatment exhibiting a partial reversal of this situation, particularly at specific frequencies and intensity levels. Apelin treatment leads to a significant increase in total antioxidant status (TAS) and a reduction in total oxidant status (TOS) and oxidative stress index (OSI) in cochlea compared to diabetic groups. The levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1 beta) in cochlear tissue were found to be significantly reduced in the apelin-treated group compared to the diabetic group. ConclusionApelin-13 may have a protective effect on the auditory system and may be proposed as a potential new therapeutic strategy for the management diabetic auditory impairment.

Effects of Free or Immobilized Pediococcus acidilactici ORE5 on Corinthian Currants on Gut Microbiome of Streptozotocin-Induced Diabetic Rats

The present study aimed to investigate the effect of a dietary intervention including free or immobilized cells of the presumptive probiotic Pediococcus acidilactici ORE5 on Corinthian currants, a food with beneficial impact in the condition of Type-1 Diabetes Mellitus (T1DM), on the microbiome composition of STZ-induced diabetic rats. Twenty four male Wistar rats were divided into four groups (n = 6 per group): healthy animals, which received the free (H_FP) or the immobilized Pediococcus acidilactici ORE5 cells (H_IPC), and diabetic animals, which received the free (D_FP) or the immobilized Pediococcus acidilactici ORE5 cells(D_IPC) for 4 weeks (109 cfu/day, in all groups). At the end of the dietary intervention, the D_IPC group exerted a lower concentration of the inflammatory cytokine IL-1 beta compared to D_FP. Consumption of immobilized P. acidilactici ORE5 cells on Corinthian currants by diabetic animals led to increased loads of fecal lactobacilli and lower Enterobacteriaceae, coliforms, and Escherichia coli levels, while Actinobacteria phylum, Akkermansia, and Bifidobacterium genera abundances were increased, and fecal lactic acid was elevated. Overall, the results of the present research demonstrated that functional ingredients could ameliorate gut dysbiosis present in T1DM and could be used to design dietary patterns aiming at T1DM management. However, well-designed clinical trials are necessary, in order to confirm the beneficial effects in humans.

Preparation of bee venom-loaded chitosan nanoparticles for treatment of streptozotocin-induced diabetes in male Sprague Dawley rats

BackgroundDiabetes mellitus (DM) can be defined as an increase in the blood sugar level and a disturbance in protein, fat and carbohydrate metabolism. Bee venom (BV) is useful for treating and preventing diabetic rats’ histological and biochemical problems. Although the medical advantages of BV have been identified, its safety has remained a substantial barrier for its application. Consequently, the goal of our work was to prepare bee venom-loaded chitosan (BV-CS) nanoparticles (NPs), which would then be physically characterized. This was followed by examining the effect of the synthetized BV-CS NPs on oxidation, inflammation and coagulation in vitro. In diabetic rats’ model [induced by streptozotocin (STZ)], the produced BV-CS NPs were tested as an anti-diabetic medication.ResultsIn vivo testing on pancreatic tissue homogenates showed that BV-CS NPs have antioxidant and anti-inflammatory properties. The results showed that BV-CS NPs can be used as a safe and efficient therapy for diabetes. Up to a concentration of 250 µg/ml, the generated NPs demonstrated potential antioxidant, membrane stabilizing, and non-cytotoxic capabilities. Our findings indicated that the administration of BV-CS NPs significantly controlled blood glucose levels and metabolic abnormalities that accompanied diabetes induction.ConclusionsBV-CS NPs were successful in treating STZ-induced diabetes in rats, stimulated insulin secretion and were safe to be used in vivo.Graphical abstract

A comparison of the Anti-diabetic Potential of Magnetized Water, Metformin, and Their Combination in A Rat Model of Type II Diabetes

DM is a collection of metabolic disorders brought on by abnormalities in secretion, action, or combination of both of insulin. Nowadays, many efforts are made to change lifestyles to get a moderate outcome with the fewest possible side effects and reduce complications. Although magnetized water (MW) has been promoted since 1930s, it has not received wide approbation since its effectiveness is still in question; however, the therapeutic potential of MW on the body has been reported. This study investigated the impact of MW supplementation on glucose, insulin, antioxidant status, inflammatory condition, DNA fragmentation and gene expression associated with the metabolism of glucose in STZ-induced diabetes in rats. Adult female Wistar rats (6 groups) were used in this study: G1: Control group+ tap water (TW); G2: Control group+ MW; G3: Diabetic group+ TW; G4: Diabetic group+ MW; G5: Diabetic group+ metformin (Met)+ TW; G6: Diabetic group+ Met+ MW. Additionally, lowering serum glucose and raising insulin level, MW consumption repaired DNA damage, enhanced antioxidant status, reduced inflammatory response, and upregulated genes linked to glucose metabolism. Furthermore, as shown by the histological analysis of pancreatic tissue sections, supplementation with MW could reverse the detrimental effects of STZ on the pancreas. This study offers novel insights into how MW consumption can help reduce T2DM by reducing hyperglycemia, restoring the equilibrium between antioxidants and oxidants, reducing inflammatory responses, and altering genes involved in glucose metabolism. Therefore, MW may be used as an adjuvant in T2DM management.

Acute effects of empagliflozin on open-loop baroreflex function and urine output in streptozotocin-induced type 1 diabetic rats

Although sympathetic suppression is considered one of the mechanisms for cardioprotection afforded by sodium–glucose cotransporter 2 (SGLT2) inhibitors, whether SGLT2 inhibition acutely modifies sympathetic arterial pressure (AP) regulation remains unclear. We examined the acute effect of an SGLT2 inhibitor, empagliflozin (10 mg/kg), on open-loop baroreflex static characteristics in streptozotocin (STZ)-induced type 1 diabetic and control (CNT) rats (n = 9 each). Empagliflozin significantly increased urine flow [CNT: 25.5 (21.7–31.2) vs. 55.9 (51.0–64.5), STZ: 83.4 (53.7–91.7) vs. 121.2 (57.0–136.0) μL·min−1·kg−1, median (1st–3rd quartiles), P < 0.001 for empagliflozin and STZ]. Empagliflozin decreased the minimum sympathetic nerve activity (SNA) [CNT: 15.7 (6.8–18.4) vs. 10.5 (2.9–19.0), STZ: 36.9 (25.7–54.9) vs. 32.8 (15.1–37.5) %, P = 0.021 for empagliflozin and P = 0.003 for STZ], but did not significantly affect the peripheral arc characteristics assessed by the SNA–AP relationship. Despite the significant increase in urine flow and changes in several baroreflex parameters, empagliflozin preserved the overall sympathetic AP regulation in STZ-induced diabetic rats. The lack of a significant change in the peripheral arc may minimize reflex sympathetic activation, thereby enhancing a cardioprotective benefit of empagliflozin.

Ameliorative activity of standardized Coccoloba uvifera leaves extract against streptozotocin-induced diabetic rats via activation of IRS-1/PI3K/AKT/GLUT2 pathway in liver

BackgroundCoccoloba uvifera L. (Family: Polygonaceae) known as sea grape is natively distributed in middle and south America. The aqueous leaf extract showed inhibitory activities against α-glucosidase and α-amylase in previous reports. Moreover, the hydroalcoholic leaves extract ameliorated hyperglycemia in the oral glucose tolerance test. Despite these promising results, the extracts used in these studies were not standardized, nor was their mechanism of action elucidated. The current study aims to standardize the ethanolic C. uvifera leaves extract (CU) using markers, and assess its ameliorative activity against diabetes and its hepatoprotective activity against diabetic complications.ResultsStandardized leaves’ ethanolic extract contained 0.09 ± 0.00057 and 0.23 ± 0.0011 mg/g gallic acid and rutin, respectively, as estimated by HPLC. Administration of CU (100, 200 and 400 mg/kg) for 6 weeks ameliorated DM manifestations in STZ-induced diabetic rats in a dose-dependent manner. The ethanolic extract reduced fasting blood glucose, increased serum insulin and reduced elevated liver enzymes. CU counteracted oxidative stress, promoted glucose metabolizing enzymes and reduced gluconeogenesis enzymes. The underlying mechanism involved increased expression of IR, IRS-1, IRS-2 and GLUT2 in liver tissue through activation of PI3K/AKT signaling. The histopathological study demonstrated reduced inflammation and hepatocyte degeneration.ConclusionCU could be used as a promising antidiabetic drug with hepatoprotective activity in diabetes hepatic complications. The standardized CU ethanolic extract should be further assessed clinically alone or in combination with other antidiabetic remedies.