Streptozocin-induced Diabetic Rats Research Articles

The Effect of Post-treatment with Yellow Bitter Yam (Dioscorea dumetorum) on the Antioxidant Status of Streptozocin-induced Diabetic Rats

The Effect of Post-treatment with Yellow Bitter Yam (Dioscorea dumetorum) on the Antioxidant Status of Streptozocin-induced Diabetic Rats

Glycemic homeostasis of ultrasound-assisted Murraya koenigii (Linn.) Spreng. bark extract in streptozocin-induced diabetes in rats

AbstractNumerous diseases have been linked to oxidative stress, emphasizing its role in pathogenicity. This study employed an ultrasound-assisted extraction process to obtain extracts from the bark of Murraya koenigii (L) Spreng. A thorough analysis was conducted on these dry extracts to determine their total phenolic and flavonoid content across four solvent fractions: n-hexane, ethyl acetate, n-butanol, and aqueous. Among the solvent fractions, ethyl acetate and n-butanol showed higher levels of total flavonoid content (TFC) and total phenolic content (TPC) compared to the others. The ethyl acetate fraction displayed the highest TPC (58.27 ± 4.20 mg GAE/g) and TFC (878.67 ± 40.38 mg QE/g) at 250 µg/mL concentration. Furthermore, the in-vitro antioxidant capacity of the ethyl acetate fraction was assessed for its ability to scavenge DPPH and hydrogen peroxide, revealing a concentration-dependent effect with IC50 values of 154.6 ± 6.2 and 55.12 ± 4.28 μg/mL, respectively. In a controlled experiment using streptozocin-induced diabetic rats, administering UMBE-EA at doses of 100 and 200 mg/kg notably improved blood glucose levels and body weight. Furthermore, several biochemical indicators, such as total protein levels, serum insulin, and the activities of enzymes like SGOT, SGPT, and ALP, as well as liver glycogen, showed significant enhancements. The antioxidant enzyme activities, including SOD, CAT, and GSH, returned to more favorable levels, and TABAR levels were normalized. In conclusion, the findings from this study strongly suggest that UMBE-EA possesses substantial anti-diabetic efficacy in Wistar rats, primarily attributed to its remarkable antioxidant properties and capacity to scavenge free radicals. These results provide valuable insights into the potential therapeutic benefits of UMBE-EA in diabetes management.

Antidiabetic effect of the mixture of Cissus polyantha and Rytigynia senegalensis in high-fat diet and streptozocin-induced diabetic rats

BackgroundIn traditional Chinese medicine (TCM) practices, many plants of the Cissus and Rytigynia genera are used to treat many diseases including diabetes mellitus.The aim of this study was to evaluate the modulating effects of the mixture of the aqueous extracts of Cissus polyantha and Rytiginia senegalensis (CPRS) on some enzymes of carbohydrate metabolism, oxidative profile, and cardiovascular parameters in diabetic rats. MethodsDiabetes was induced by a diet enriched in high-fat for 30 days associated with a single intraperitoneal injection of streptozocin (35 mg/kg). Rats with a blood glucose level greater than or equal to 200 mg/dL were selected and divided into groups. Groups 1 and 2 received distilled water. Group 3 received metformin (40 mg/kg). Groups 4 and 5 received CPRS at doses of 50 and 111 mg/kg, respectively. Glycaemia, body mass, food and water intake, insulinemia, insulin resistance and insulin secretion indices, lipid profile and cardiovascular risk indices, oxidant profile, glycogen and liver enzymes were evaluated. Histology of the pancreas and heart was performed. ResultsCPRS (50 and/or 111 mg/kg) significantly (p < 0.05 to p < 0.001) reduced water and food consumption, blood glucose, HOMA-IR, coronary risk index, cholesterol, triglyceride, LDL-c, VLDL-c, and malondialdehyde levels, as well as glucose-6-phosphatase and fructose-1,6-biphosphatase activities in diabetic animals. In contrast, CPRS (50 and/or 111 mg/kg) caused an increase (p < 0.05 to p < 0.001) in body mass, insulinemia and HDL-c levels, reduced glutathione and hepatic glycogen. HOMA-β, insulin distribution, atherogenic and cardioprotective indices as well as superoxide dismutase, catalase, glucokinase, and glucose-6-phosphate dehydrogenase activities were also increased after CPRS administration. CPRS regenerated pancreatic islet β cells and decreased leukocyte infiltration in cardiomyocytes of diseased animals. ConclusionCPRS has hypoglycemic, antidyslipidemic, and antioxidant effects, thus validating its use in traditional medicine in the treatment of diabetes mellitus and its complications.

Identification and Validation of the Pyroptosis-Related Hub Gene Signature and the Associated Regulation Axis in Diabetic Keratopathy.

Diabetic keratopathy (DK) poses a significant challenge in diabetes mellitus, yet its molecular pathways and effective treatments remain elusive. The aim of our research was to explore the pyroptosis-related genes in the corneal epithelium of the streptozocin-induced diabetic rats. After sixteen weeks of streptozocin intraperitoneal injection, corneal epithelium from three diabetic rats and three normal groups underwent whole-transcriptome sequencing. An integrated bioinformatics pipeline, including differentially expressed gene (DEG) identification, enrichment analysis, protein-protein interaction (PPI) network, coexpression, drug prediction, and immune deconvolution analyses, identified hub genes and key drivers in DK pathogenesis. These hub genes were subsequently validated in vivo through RT-qPCR. A total of 459 DEGs were screened out from the diabetic group and nondiabetic controls. Gene Set Enrichment Analysis highlighted significant enrichment of the NOD-like receptor, Toll-like receptor, and NF-kappa B signaling pathways. Intersection of DEGs and pyroptosis-related datasets showed 33 differentially expressed pyroptosis-related genes (DEPRGs) associated with pathways such as IL-17, NOD-like receptor, TNF, and Toll-like receptor signaling. A competing endogenous RNA network comprising 16 DEPRGs, 22 lncRNAs, 13 miRNAs, and 3 circRNAs was constructed. After PPI network, five hub genes (Nfkb1, Casp8, Traf6, Ptgs2, and Il18) were identified as upregulated in the diabetic group, and their expression was validated by RT-qPCR in streptozocin-induced rats. Immune infiltration characterization showed that diabetic corneas owned a higher proportion of resting mast cells, activated NK cells, and memory-resting CD4 T cells. Finally, several small compounds including all-trans-retinoic acid, Chaihu Shugan San, dexamethasone, and resveratrol were suggested as potential therapies targeting these hub genes for DK. The identified and validated hub genes, Nfkb1, Casp8, Traf6, Ptgs2, and Il18, may play crucial roles in DK pathogenesis and serve as therapeutic targets.

Hypoglycemic and Hepatoprotective Activities of Coriander (Coriandrum sativum) Extract in Streptozocin Induced Diabetic Rats

The present study was designed to evaluate the role of Coriander (Coriandrum sativum) for management of diabetes instead of manufactured drugs, which led to many complications. Medicinal plants would be higher useful for this purpose because they are considered to be effective and non-toxic and safer than manufactured drugs. Aqueous extract of Coriander (C. sativum) was used to measurements their antidiabetic and hepatoprotective effects in streptozocin (STZ) induced diabetic male albino rats. Coriander (C. sativum) was given to the STZ induced diabetic rats at the concentration of 200 mg/kg body weight in different groups of three diabetic rats each orally once a day for 15 days. Body weight showed significant increase after 15 days of treatment with Coriander (C. sativum) extract compared with the normal control rats group (N). Blood glucose level on 15th day of treatment became significantly lower. The extract induced significant reduction in serum glucose, total lipids, total cholesterol, triglycerides level and transaminases (AST, ALT and γ-GT) activities. Liver glycogen content was significantly increased in treated animals compared to control group (N). The present data revealed insignificant changes in the serum total protein, albumin and globulin level during the experimental period. The lipid peroxidation determined was found to be decreased in plasma, liver and kidney of streptozocin induced diabetic rats treated with Coriander (C. sativum) extract (STZ/T) and rats group given Coriander (C. sativum) extract and then induced streptozocin (T/STZ), compared to control streptozocin induced diabetic rats group (STZ©). Glutathione reductase (GSH-R), glutathione peroxidase (GSH-P) and superoxide dismutase (SOD) activities were increased in liver and kidney of rat groups. These findings demonstrates that Coriander (C. sativum) extract have antioxidant effect for reducing lipid peroxidation in plasma and tissues and improve the liver function and antioxidant enzymes in treated rat groups compared to diabetic control rat group (STZ©). These observations revealed that the use of Coriander (C. sativum) extract can be recommended as natural antidiabetic, antioxidant and hypolipidemic activity agent. Findings of the present study suggest that the aqueous extract of Coriander (C. sativum) at the dose of 200 mg/kg body weight brings about significant beneficial effects in various biochemical parameters during diabetic and these effects are quite comparable with standard drug used to treat diabetes mellitus.

Reduced Progression of Diabetic Nephropathy in Streptozocin-Induced Diabetic rats by Lannea coromandelica Leaf Extract

Objectives: An important contributor to end-stage renal failure globally is diabetic kidney disease. The current study looked at the safeguarding results of an infusion of Ethanol from Lannea coromandelica houtt leaves (ELCL)in diabetic kidney disease that was caused by streptozotocin with the intention to treat diabetic nephropathy, creating supportive and substitute medicine is necessary. The development of DN may be slowed down by itsanti-inflammatory, anti-diabetic and antioxidant qualities. The novelity lies in the plant selection for the study. Methods: Streptozotocin (45mg/kg, i.p.) was administered as a single dosage to rats to induce diabetes. During 8 weeks, oral dosages of ELCL (100mg/kg and 200mg/kg.) were given to rodents with STZ diabetes. Blood sugar amounts and body and kidney weights were measured at the conclusion of the trial period. The parameters of serum and urine were evaluated. The kidney levels of lipid peroxide and antioxidant enzymes were assessed. Results: In STZ-diabetic rats and rats treated with extract, ethylacetate extract dramatically raised body weight and decreased blood glucose, blood urea levels, blood nitrogen levels, and the creatinine levels. All kidney antioxidants, including glutathione synthetase, glutathione-S-transferase, catalase, superoxide dismutase and NAD(P) H dehydrogenase [quinone]1 were highly upregulated by the extract. Conclusion: According to research, ELCL may have antioxidant, antihyperglycemic, and anti-glycation properties that could slow the progression of diabetic nephropathy.

The Safety and Efficacy of Combining Saxagliptin and Pioglitazone Therapy in Streptozocin-Induced Diabetic Rats.

Type 2 diabetes mellitus (T2DM) is a chronic progressive disease due to insulin resistance. Oxidative stress complicates the etiology of T2DM. Saxagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor, while Pioglitazone is a thiazolidinedione insulin sensitizer. This study aimed to assess the effect of Saxagliptin and Pioglitazone monotherapy and combination therapy on the biochemical and biological parameters in streptozotocin (STZ)-induced diabetic rats. The study included thirty-five male albino rats. Diabetes mellitus was induced by intraperitoneal STZ injection (35 mg/kg). For a 1-month duration, rats were divided into five groups. Glucose homeostasis traits, lipid profiles, kidney functions, liver enzymes, and oxidative stress markers were measured. Gene expression of miRNA-29a, phosphoenolpyruvate carboxykinase (PEPCK), phosphoinositide-3-kinase (PI3K), and interleukin 1 beta (IL-1β) was assessed using qRT-PCR. At a 1-month treatment duration, combination therapy improves oxidative stress markers more than either drug alone. The combination therapy had significantly higher levels of SOD, catalase, and GSH and lower levels of MDA compared to the monotherapy. Additionally, the diabetic group showed a significant increase in the expression levels of miRNA-29a, PEPCK, and IL-1β and a significant decrease in PI3K compared to the normal control group. However, combination therapy of Saxagliptin and Pioglitazone was more effective than either Saxagliptin or Pioglitazone alone in reversing these results, especially for PEPCK and IL-1β. Our findings revealed that combining Saxagliptin and Pioglitazone improves glycemic control and genetic and epigenetic expression profiles, which play an essential regulatory role in normal metabolism.

Metformin Preserves Insulin Secretion in Pancreatic β-cells through FGF21/Akt Pathway In vitro and In vivo.

In our previous studies, it was found that metformin can elevate the expression of FGF21 in the peripheral blood of type 2 diabetic rats and improve insulin sensitivity in diabetic rats. However, whether this effect is mediated by increased FGF21 expression in pancreatic islet β-cells is still unknown. Therefore, this study focuses on the effect of metformin on insulin secretion in pancreatic β-cells. Metformin can effectivly improve insulin resistance. Metformin influencing pancreatic βcell function is inclusive. In this study, we sought to analyze possible variations in insulin secretion and possible signaling mechanisms after metformin intervention. The study employed an in vivo model of a high-fat diet in streptozocin-induced diabetic rats and an in vitro model of rat pancreatic β-cells (INS-1 cells) that were subjected to damage caused by hyperglycemia and hyperlipidemia. After treating INS-1 cells in normal, high-glucose, and high-glucose+metformin, we measured insulin secretion by glucose-stimulated insulin secretion (GSIS). Insulin was measured using an enzyme-linked immunosorbent assay. FGF21 expression was detected by RT-PCR and Western blot, as well as that p-Akt and t-Akt expression were detected by Western blot in INS-1 cells and diabetic rat islets. Finally, to verify the regulation of the FGF21 /Akt axis in metformin administration, additional experiments were carried out in metformin-stimulated INS-1 cells. High-glucose could significantly stimulate insulin secretion while metformin preserved insulin secretion. Expression of FGF21 and p-Akt was decreased in high-glucose, however, metformin could reverse this effect in INS-1 cells and diabetic rat islets. Our results demonstrate a protective role of metformin in preserving insulin secretion through FGF21/Akt signaling in T2DM.

SAT072 Choline Deprivation Aggravates Hyperglycemia And Fatty Liver In Non-obese Streptozocin-induced Diabetic Rats

Abstract Disclosure: C. Liapi: None. A. Kyriakaki: None. H. Al Humadi: None. R. Al-Saigh1: None. A. Al Humadi: None. A. Lazaris: None. Background: Choline deprivation (CD) is an established model of steatohepatitis. There is a strong association between non-alcoholic fatty liver disease and diabetes mellitus that has a significant impact on the global health system. The combined state of CD and diabetes can resemble common cases in clinical practice including parenteral nutrition, pregnancy, chronic liver disease malnutrition and/ or alcoholism in diabetic individuals. The aim of this study was to investigate the effects of choline deprivation on glycemic control, insulin signaling pathway and lipid metabolism in non-obese streptozocin-induced diabetic rats. Methods: Thirty-two male adult Wistar rats were divided into four groups; control, diabetes (DM), choline-deprived diet (CDD), and combined group (DM+CDD); DM was induced by intraperitoneal streptozotocin administration. Body weight, fasting blood glucose and plasma insulin levels, lipid profile, liver biochemistry, liver histopathology and gene expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), glucose transporters 2 &amp; 4 (GLUT-2 &amp; -4) in hepatic tissue, were assessed. Results: The combination group (CDD+DM) showed a significant increase in blood glucose associated with a significant decrease in plasma insulin level and evidence of dyslipidemia with a significant increase in liver enzymes, histopathology showed extensive micro- and macrovesicular steatosis and a significant decrease in weight gain versus the control, CDD and DM group. A significant increase was observed in gene expression of IR, IRS-1, GLUT-2, and GLUT-4 in all the experimental groups versus the control. Conclusion: The combination of choline deficiency and diabetes has drawn some new scenarios on insulin and some hepatic metabolic pathways: (i) plasma insulin resistance with progressive hyperglycemia and hyperlipidemia.(ii) attenuation of hepatic insulin resistance or sensitization of insulin signaling pathways in the liver, due to the hepatotoxic effects of choline deficiency that could ultimately simulate features of the metabolic syndrome, and (iii) experimentally simulation of metabolic conditions seem to act synergistically, leading to poor glycemic control along with aggravation of hepatic steatosis. Presentation: Saturday, June 17, 2023

Beneficial effects of protocatechuic acid on diabetic retinopathy in streptozocin-induced diabetic rats.

To determine the effects of protocatechuic acid (PCA) on streptozocin-induced diabetic retinopathy (DR) in rats. Wistar rats were given a 50 mg/kg intraperitoneal injection of streptozocin to induce diabetes. Animals were assigned randomly one of four groups (8 rats per group): control, diabetic, diabetic plus PCA (25 mg/kg·d), and diabetic plus PCA (50 mg/kg·d). After inducing diabetes, treatments were started one week later and continued for eight weeks. After the experiment, the rats were sacrificed, and their retinas were taken for biochemical and molecular analysis. PCA administration diminished the blood glucose and glycated haemoglobin levels relative to the diabetic group. In diabetic rats, PCA lowered elevated levels of advanced glycosylated end products (AGEs) and receptor for AGEs (RAGE). In the retina of diabetic rats, PCA effectively decreased inflammatory cytokine, nuclear factor-κB, tumour necrosis factor-α, interleukin-1β, and vascular endothelial growth factor, and increased antioxidant markers glutathione, superoxide dismutase, and catalase. The protective benefits of PCA against DR may be attributable to its suppression of the AGEs and RAGE and its antioxidant and anti-inflammatory properties.

The Protective Effects of Aloe Vera Gel Extract on the Sexual Complications Caused by Diabetes in Male Rats

Introduction: Diabetics usually suffer from chronic complications, including microvascular and macrovascular disorders. The capillaries supplying the sexual organs affect normal sexual functions. The erectile process has been shown to be impaired in diabetics. Vascular damage in diabetics may be associated with decreased testosterone production, sperm count, testicular weight, and seminiferous tubule diameter. In this study, we investigated the effects of Aloe vera gel extract (from Sistan and Baluchistan, Iran) on the male genital system in streptozocin-induced diabetic rats. Methods: A total of 24 male Wistar rats were included in the study. Diabetes was induced in 12 rats by intraperitoneal injection of a single dose of streptozotocin (STZ). The rats were divided into four groups. The first and third groups received saline (NaCl) by gavage daily. The second and fourth groups received Aloe vera gel extract daily by gavage. Treatments were continued for 30 days. At the end of the treatment period, blood samples were taken and serum glucose and testosterone levels were measured by photometric methods. Histological examinations were performed on the prostate and testes. Results: Mean weight index, serum levels of glucose and testosterone, mean sperm count, germinal epithelium (GE) thickness, and seminiferous tubule diameter improved significantly in the diabetes+Aloe vera group. Conclusion: We concluded that consumption of Aloe vera gel extract improved sexual complications in diabetic rats.

Nicotinamide Riboside Improves Enteric Neuropathy in Streptozocin-Induced Diabetic Rats Through Myenteric Plexus Neuroprotection.

Diabetes Mellitus causes a systemic oxidative stress due in part to the hyperglycemia and the reactive oxygen species generated. Up to 75% of diabetic patients present with an autonomic neuropathy affecting the Enteric Nervous System. Deficits in the human population are chronic dysmotilities with either increased (i.e., constipation) or decreased (i.e., diarrhea) total gastrointestinal transit times. These are recapitulated in the streptozocin-induced diabetic rat, which is a model of Type I Diabetes Mellitus. Examine the effects that a precursor of nicotinamide adenosine dinucleotide (NAD), nicotinamide riboside (NR), had on the development of dysmotility in induced diabetic rats and if fecal microbiota transplant (FMT) could produce the same results. Utilizing a 6-week treatment paradigm, NR was administered intraperitoneally every 48h. Total gastrointestinal transit time was assessed weekly utilizing the carmine red method. Three weeks following hyperglycemic induction, FMT was performed between NR-treated animals and untreated animals. There is improvement in overall gastrointestinal transit time with the use of NR. 16S microbiome sequencing demonstrated decreased alpha and beta diversity in induced diabetic rats without change in animals receiving FMT. Improvements in myenteric plexus ganglia density in small and large intestines in diabetic animals treated with NR were seen. NR treatment led to functional improvement in total gastrointestinal transit time in induced diabetic animals. This was associated with neuroprotection in the myenteric plexuses of both small and large intestines of induced diabetic rats. This represents an important first step in showing NR's benefit as a treatment for diabetic enteric neuropathy. Streptozocin-induced diabetic rats have improved transit times and increased myenteric plexus ganglia density when treated with intraperitoneal nicotinamide riboside.

Wound healing activity of Salvia huberi ethanolic extract in streptozocin-induced diabetic rats

Objective: The aim of this study was to examine the in vivo wound healing potential of Salvia huberi Hedge (endemic to Turkey) on excision and incision wound models in diabetic rats. Method: Male Wistar albino rats, 3-4 months old and weighing 180-240g were used. The animals were randomly divided into five groups including Control, Vehicle and Fito reference, and two different concentrations (0.5% and 1% weight/weight (w/w)) of ethanol extract of Salvia huberi were investigated in both wound models on streptozocin-induced diabetic rats using macroscopic, biomechanical, biochemical, histopathological, genotoxic and gene expression methods over both seven and 14 days. Fito cream (Tripharma Drug Industry and Trade Inc., Turkey) was used as the reference drug. Results: A total of 60 rats were used in this study. Salvia huberi ointments at 0.5% and 1% (w/w) concentrations and Fito cream showed 99.3%, 99.4% and 99.1% contraction for excision wounds, and 99.9%, 97.0% and 99% contraction for incision wounds, respectively. In Salvia huberi ointments and Fito cream groups, re-epithelialisation increased dramatically by both day 7 and day 14 (p<0.05). By day 14, low hydroxyproline and malondialdehyde (MDA) levels, and high glutathione (GSH) levels were observed in the Salvia huberi ointment groups. After two application periods, damaged cell percent and genetic damage index values and micronucleus frequency of Salvia huberi ointment treatment groups were lower than Control and Vehicle groups (p<0.001). A growth factor expression reached a high level by day 7 in the Control group; in Salvia huberi-treated groups it was decreased. Conclusion: The study showed that application of Salvia huberi ointments ameliorated the healing process in diabetic rats with excisional and incisional wounds and may serve as a potent healing agent.

Wound healing activity of Salvia huberi ethanolic extract in streptozocin-induced diabetic rats

Objective: The aim of this study was to examine the in vivo wound healing potential of Salvia huberi Hedge (endemic to Turkey) on excision and incision wound models in diabetic rats. Method: Male Wistar albino rats, 3-4 months old and weighing 180-240g were used. The animals were randomly divided into five groups including Control, Vehicle and Fito reference, and two different concentrations (0.5% and 1% weight/weight (w/w)) of ethanol extract of Salvia huberi were investigated in both wound models on streptozocin-induced diabetic rats using macroscopic, biomechanical, biochemical, histopathological, genotoxic and gene expression methods over both seven and 14 days. Fito cream (Tripharma Drug Industry and Trade Inc., Turkey) was used as the reference drug. Results: A total of 60 rats were used in this study. Salvia huberi ointments at 0.5% and 1% (w/w) concentrations and Fito cream showed 99.3%, 99.4% and 99.1% contraction for excision wounds, and 99.9%, 97.0% and 99% contraction for incision wounds, respectively. In Salvia huberi ointments and Fito cream groups, re-epithelialisation increased dramatically by both day 7 and day 14 (p<0.05). By day 14, low hydroxyproline and malondialdehyde (MDA) levels, and high glutathione (GSH) levels were observed in the Salvia huberi ointment groups. After two application periods, damaged cell percent and genetic damage index values and micronucleus frequency of Salvia huberi ointment treatment groups were lower than Control and Vehicle groups (p<0.001). A growth factor expression reached a high level by day 7 in the Control group; in Salvia huberi-treated groups it was decreased. Conclusion: The study showed that application of Salvia huberi ointments ameliorated the healing process in diabetic rats with excisional and incisional wounds and may serve as a potent healing agent.

Wound Healing Activity of the Flavonoid-Enriched Fraction of Selaginella bryopteris Linn. against Streptozocin-Induced Diabetes in Rats

Diabetes and its complications, such as delayed wound healing, are increasing at an alarming rate in India, putting an enormous strain on the country’s limited healthcare resources. Hence, the present study proposes to screen/identify the possible mechanisms and to study the effect of the flavonoid-enriched fraction of Selaginella bryopteris extract against human keratinocyte cell lines (HaCaT) and streptozocin (STZ)-induced diabetic wounds in a male Wistar rat model. Chemical profiling was performed by an MTT assay. The obtained GC–MS analysis results showed the presence of amentoflavone, gallic acid, imidazole, palmitic acid, catechine, L-fucitol, lupeol, and myo-inositol as the major bioactive phytoconstituents. S. bryopteris induces the generation of ROS, the condensation of chromatin in the nucleus, and changes in the membrane potential of mitochondria in HaCaT cell lines. An S. bryopteris-dependent induction of apoptosis-mediated cell death in HaCaT cell lines was confirmed by an AO/PI analysis. Mitochondrial depolarization was reflected in JC-1 staining of cells. The wound size was reduced and epithelialization was enhanced. Keratinocyte migration decreased interleukins, TNF-α, IL-2, and IL-6 and the expression of pro-apoptotic (p53, caspase-3, caspase-9, and Bax) and anti-apoptotic (Bcl-2) genes in a dose-dependent manner. Keratinocyte migration increased antioxidant enzyme levels (CAT, SOD, MDA, and GSH). Wound healing is facilitated through the mitochondria-mediated apoptosis pathway, revealing a new area of diabetic wound therapy.

Onopordum acanthium L. extract attenuates pancreatic β-Cells and cardiac inflammation in streptozocin-induced diabetic rats.

Methanolic extract from Onopordum acanthium L. leaves (MEOAL) has been discovered to treat diabetic complications. The objective of this study is to evaluate the ameliorative role of MEOAL on pancreatic islet injury and myocardial inflammation in diabetic rats. Forty male Wister albino rats were allocated into five groups of eight rats each. Group A was the negative control group. Single intraperitoneal injection of streptozocin (50mg/kg) were used for the four experimental groups. Group B served as the positive control group. The rats in Groups C, D, and E received glibenclamide (5mg/kg), MEOAL (200, and 400 mg/kg) respectively, for eight weeks. Group C served as the standard drug group. High performance liquid chromatography (HPLC) and 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assays for antioxidant activity were conducted in MEOAL. In silico study, calculation of molecular binding energy (DG), and inhibition constant (pKi) of bioactive constituents in MEOAL were performed. Administration of MEOAL significantly increases insulin content in β-cells with a marked enhancement of pancreatic islet structure, resulting in a significant reduction of blood glucose level and body weight loss. MEOAL treatment suppressed the increase of inflammatory cell score in myocardial tissue with an elevation of M2 -like macrophage. The phytochemical studies recorded the presence of six polyphenols, including catechin, kaempferol, syringic acid, p-coumaric acid, epicatechin and gallic acid in MEOAL. Moreover, the antioxidant activity of the extract was greater than that of standard ascorbic acid. The docking studies of the ligands Catechin, kaempferol and epicatechin with proteins showed high affinities with various targets related in β-Cells and cardiac inflammation. The attenuation of pancreatic β-Cells damage and cardiac inflammation by MEOAL could be attributed to the presence of Catechin, kaempferol and epicatechin which have high affinities with the receptors namely pancreatic alpha-amylase, glucokinase, COX-2, and COX-1.

Synergic effects of Trigonella foenum-graecum, Ribes rubrum, Lavandula angustifolia, and Arctium Lappa extracts mixture on learning and memory deficits in streptozocin-induced diabetic rats.

The present study aimed to assess the efficacy of some known extracts on learning and memory impairment induced by streptozocin (STZ) in male rats. Eighty male rats were randomly divided: 1) control, 2) STZ (50 mg/kg), 3) STZ+Trigonella foenum-graecum (200 mg/kg), 4) STZ+Ribes rubrum (500 mg/kg), 5) STZ+Lavandula angustifolia (400 mg/kg), 6) STZ+Arctium Lappa (200 mg/kg), 7) STZ+mix of extracts (quarter dose of each extract), and 8) STZ+metformin (100 mg/kg). Treatment was continued for 8 weeks and the after that, the behavioral tests related to learning and memory including Morris water maze (MWM) and passive avoidance (PA) were performed along with biochemical analysis associated with oxidative stress pathway and other related indicators. According to the results, all extracts demonstrated potential effect to ameliorate cognitive impairment caused by STZ in both MWM and PA tests along with attenuating oxidative stress indicators like malondialdehyde (MDA), while total thiol content and anti-oxidant enzyme activity like superoxide dismutase (SOD) and Catalase (CAT) remarkably increased in biochemical test results. Interestingly, the mixture of extracts illustrated much better results in ameliorating the brain-derived neurotrophic factor (BDNF), while attenuating the amyloid-B and glial fibrillary acidic protein (GFAP). The present study demonstrated these extracts alone or in combination with a minimum dose have a strong potential to ameliorate learning and memory impairment induced by STZ along with lowering glucose levels by which they prevent or manage diabetes. It is noteworthy that the results matched those of metformin a well-known anti-diabetic drug.

The Effects of Systemic Coenzyme Q10 Treatment on Corneal Histology in Streptozocin-Induced Diabetic Rats

ABSTRACT Objective This study investigate the histopathological changes and VEGF, IL-1β, and IL-6 immunoreactivities in cornea treated with Coenzyme Q10 (CoQ10) in a Streptozocin (STZ) induced diabetic rat model. Methods A total of 20 male Wistar Albino rats including a group of STZ diabetic rats, diabetic rats treated with CoQ10, rats were given CoQ10 without being diabetic and a Control group were included the study. The groups were followed up for 2 months. Eye tissues were stained with Hematoxylin-Eosin (HE), Periodic Acid-Schiff (PAS), and immunohistochemical staining (IHC). Findings The mean corneal thickness was found to be lower in the group with DM (126,62 ± 18,1) compared to the other groups. However, this decrease was found to be significant only in comparison with the control group (181,75 ± 13,87) (p = 0.000). In diabetic corneas, PAS positivity was observed in in Descemet's membrane (p = 0.021). Staining with VEGF, IL-1β, IL-6antibodies was found to be lower in the DM+CoQ10 group compared to the group with DM (p < 0.001, p < 0.001, p < 0.001). Results We observed that diabetes increases inflammation and tendency to angiogenesis in the corneal tissue, and CoQ10 treatment reduces the corneal thickness, inflammation, and tendency to angiogenesis caused by diabetes.

Antidiabetic activity of Solanum torvum fruit extract in streptozotocin-induced diabetic rats.

Solanum torvum Swartz, a medicinal plant belonging to the family Solanaceae, is an important medicinal plant widely distributed throughout the world and used as medicine to treat diabetes, hypertension, tooth decay, and reproductive problems in traditional systems of medicine around the world including Malaysia. The objective of this study was to investigate hypoglycemic, antilipidemic, and hepatoprotective activities, histopathology of the pancreas, and specific glucose regulating gene expression of the ethanolic extract of S. torvum fruit in streptozotocin-induced diabetic Sprague-Dawley rats. Acute toxicity study was done according to OECD-423 guidelines. Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg) in male Sprague-Dawley rats. Experimental diabetic rats were divided into six different groups; normal, diabetic control, and glibenclamide at 6 mg/kg body weight, and the other three groups of animals were treated with oral administration of ethanolic extract of S. torvum fruit at 120, 160, and 200 mg/kg for 28 days. The effect of ethanolic extract of S. torvum fruit on body weight, blood glucose, lipid profile, liver enzymes, histopathology of pancreas, and gene expression of glucose transporter 2 (slc2a2), and phosphoenolpyruvate carboxykinase (PCK1) was determined by RT-PCR. Acute toxicity studies showed LD50 of ethanolic extract of S. torvum fruit to be at the dose of 1600 mg/kg body weight. Blood glucose, total cholesterol, triglycerides, low-density lipoproteins, very low-density lipoproteins, serum alanine aminotransferase, and aspartate aminotransferase were significantly reduced, whereas high-density lipoproteins were significantly increased in S. torvum fruit (200 mg/kg)-treated rats. Histopathological study of the pancreas showed an increase in number, size, and regeneration of β-cell of islets of Langerhans. Gene expression studies revealed the lower expression of slc2a2 and PCK1 in treated animals when compared to diabetic control. Ethanolic extract of S. torvum fruits showed hypoglycemic, hypolipidemic, and hepatoprotective activity in streptozocin-induced diabetic rats. Histopathological studies revealed regeneration of β cells of islets of Langerhans. Gene expression studies indicated lower expression of slc2a2 and PCK1 in treated animals when compared to diabetic control, indicating that the treated animals prefer the gluconeogenesis pathway.

Preliminary Feasibility Study on Diffusion Kurtosis Imaging to Monitor the Early Functional Alterations of Kidneys in Streptozocin-Induced Diabetic Rats

The aim of this study was to investigate the potential of diffusion kurtosis imaging (DKI) to assess the early renal functional undulation of diabetic mellitus (DM). Fifty-seven Sprague-Dawley (SD) rats were randomly divided into two groups and eventually 48 rats were included in this study: the normal control (CON) group and diabetic mellitus (DM) group. Weeks 0, 4, 8, and 12 after the diabetes model was successfully established, all the rats were scanned on the 3.0T MRI. The DKI derived parameters of renal parenchyma, including fractional anisotropy (FAco, FAme), mean diffusivity (MDco, MDme), and mean kurtosis (MKco, MKme) were measured. Their alteration over time was analyzed and then correlated with urine volume (UV), blood urea nitrogen (BUN), and serum creatinine (Scr) using Pearson correlation analysis. Finally, hematoxylin and eosin (H&E) staining was performed on the kidneys of the two groups. There was a decreasing trend in FA, MK, and MD values over time in diabetic rats. Also, the gradually worsening histological damage of kidneys was noted over time in diabetic rats. The cortical FA and MK values and medullary FA, MK and MD values of diabetic rats were significantly lower than those of controls at most time points after DM induction. In addition, negative correlations were revealed between the BUN and FAco (r=-0.43, p = 0.03) or FAme value (r=-0.49, p = 0.01). The cortical MK value was moderately correlated with UV (r=-0.46, p = 0.03) and BUN (r=-0.55, p = 0.01). The preliminary findings suggest that DKI might be an effective and sensitive tool to assess the early changes of renal function impairment in diabetic rats. The FA values of the cortex and medulla and the MK value of the cortex are sensitive markers in detecting renal injury in diabetic rats.