STZ-induced Diabetic Wistar Rats Research Articles

Paris polyphylla Sm. characterized extract infused ointment accelerates diabetic wound healing in In-vivo model

Ethnopharmacological relevanceThe dried rhizome of Paris polyphylla Sm. is extensively used by traditional healers in India, China, and Vietnam to treat skin inflammation, cut wounds, uterine and traumatic bleeding, and cancer. Aim of the studyThe traditional use of P. polyphylla rhizomes for treating wounds and bleeding has been reported previously. However, the potential of P. polyphylla in the treatment of diabetic wounds has not yet been explored. Our present study focused on the investigation of the wound-healing activity of P. polyphylla infused ointment in streptozotocin (STZ)-induced diabetic rats to validate the traditional claim. Materials and methodsHydroalcoholic extract of the dried rhizomes of P. polyphylla were quantified by validated and optimized HPTLC (High-performance thin layer chromatography) method for Paris saponin VII, Dioscin and Polyphyllin V. The extract was used to prepare P. polyphylla ointments (5 and 10%). P. polyphylla ointment was subjected to physiochemical analysis and skin irritation test. Thirty STZ-induced diabetic adult male Wistar albino rats were divided into five groups (n = 6) and a circular excision wound was created. P. polyphylla ointment, ointment base (OB), and standard (STD) (Povidone Iodine 10%) were administered topically. The wound area of all groups were recorded every six days and compared with that of control. The epithelization period of each group was recorded. On day 18, the histopathological study of skin tissues of all groups was performed using hematoxylin and eosin (H&E) and Mallory's trichrome (MT). ResultsMarker analysis and quantification of phytomolecules in hydroalcoholic extract ofP. Polyphylla were found to be of paris saponin VII (3.28 ± 0.08% w/w), dioscin (1.94 ± 0.12% w/w), and polyphyllin V (1.87 ± 0.84% w/w). A physiochemical study of P. polyphylla ointment showed that the prepared ointment was within an acceptable range and was not irritable to the skin. Daily topical administration of 10% P. polyphylla ointment (PP10) for 18 days completely healed the STZ-induced diabetic wounds. On day 18, the 5% P. polyphylla ointment (PP5) showed 99.1 ± 2.9% wound closure, while that of the standard and control was 78.4 ± 7.3% and 18.5 ± 5.9%, respectively. The epithelialization period of PP10 was 18 days, whereas that of the control was 28 days. Histopathological analysis of the progression of PP10 and PP5 wounds showed a decrease in inflammatory cells, regenerated epithelial layer, keratosis layer, hair follicles, fibroblasts, and collagen. Upon collagen intensity quantification of MT stained sections, an increase in collagen density of PP10 and PP5 treated groups was observed, showing accelerated wound healing potential of P. polyphylla extract in diabetic wounds compared to the standard ointment. ConclusionThis study suggested the potential of P. polyphylla rhizomes derived formulation to treat diabetic wounds, although the plant is traditionally used to treat normal wounds. The results indicate the validation of traditional claim, which has been explored commercially in industrial aspect.

Antidiabetic activity and safety evaluation of two Cameroonian medicinal plants in Streptozotocin-rat model: Tetrapleura tetraptera (Fabaceae) and Irvingiagabonensis (Irvingiaceae)

Background: Irvingia gabonensis and Tetrapleura tetraptera are widely employed by traditional healers of the southern regions of Cameroon to treat diabetes. However. there is only limited or no scientific evidence on the real potential of these two medicinal plants to serve as alternative therapies. The present works thus aimed to evaluate the antidiabetic activity of the barks of I. gabonensis and fruits of T. tetraptera. Methods: The antidiabetic potential of the four extracts was assessed by evaluating the hypoglycaemic activity through the oral glucose tolerance test (OGTT) in male Wistar albino rats and the subacute antidiabetic assay in streptozotocin-induced Wistar rat model. For the later. clinical markers (water and food intake, urine excretion), Fasting Blood Sugar FBS), the effects on some vital organs (liver and kidney), and lipid profile were considered. Safety was evaluated using the in vivo acute toxicity test in mouse model. Results: Out of the four extracts prepared from T. tetraptera and I. gabonensis, and tested for their antidiabetic potential, only the hydroethanol extract of the stem bark of I. gabonensis showed promising hypoglycemic and anti-hyperglycemic activity from preliminary screening. Of the two doses of this extract considered for the subacute antidiabetic assessment, the dose of 500mg/Kg demonstrated the highest activity reflected in significant improvement in both clinical and biochemical markers with a 100% recovery rate after 21 days treatment of the STZ-induced diabetic Wistar rats. At this dose, the I. gabonensis extract was shown to also improve liver and kidney functions as well as mitigating dyslipidemia in diabetic rats. Overall, its pharmacological properties were above those of the reference drug metformin at 10mg/Kg dose. More interestingly, the acute toxicity study revealed a relative safety of this extract in mice. Conclusion: The present work confirms the potential of the hydroethanolic extract of I. gabonensis to serve a source of new antidiabetic drugs. Further investigations are therefore envisaged.

Discovery of chalcone derivatives as potential α-glucosidase and cholinesterase inhibitors: Effect of hyperglycemia in paving a path to dementia

In the present study, a series of fascinating chalcone derivatives 1C-14C has been designed and synthesized by Claisen-Schmidt condensation. The target compounds were screened for in vitro α-glucosidase and cholinesterase inhibitory activities. For the first time, the enzyme inhibitory activities of the target derivatives were assessed for antihyperglycemic and neuroprotective activities on streptozotocin (STZ) induced diabetic animal models using in vivo mechanism-based assays. Based on α-glucosidase and cholinesterase inhibitory activities, the compounds 2C, 3C, 13C and 14C were chosen in vivo for further evaluation of antidiabetic and neuroprotective activities in STZ-induced diabetic Wistar rats. All these evaluated compounds demonstrated significant antidiabetic and antiamnesic activities and found nontoxic in nature. The target compounds were then tested in vivo for cognitive function in a STZ-induced amnesic animal paradigm, where four compounds 2C, 3C, 13C, and 14C considerably reduced the amnesic effects as measured by the Y-Maze Paradigm and novel object discrimination (NOD) tasks. Furthermore, the structure-activity relationship of these substituted chalcone derivatives was established. According to kinetic studies, 2C and 7C have Ki values of 0.017±0.00078 µM and 0.00060±0.00004 µM, respectively, and were competitive inhibitors of cholinesterase and α-glucosidase. Molecular docking study revealed that the co-crystallized ligand and potent compounds exhibited same binding orientation within the target enzyme's active site (α-glucosidase (PDB ID: 3AJ7), AChE (PDB ID: 1ACL) and BChE (PDB ID: 4TPK)). The QSAR studies were conducted based on anti-glucosidase and anti-cholinesterases (AChE, BChE) assays. The value of coefficient of multiple determinant (R2) 0.9999 depicts a strong relationship between 1C-14C structures and selected properties. Most of these substances are selective inhibitors of cholinesterase that may be used for age-related problems and to treat the progressive neurodegenerative disorder.

Taxifolin-3-O-glucoside from Osbeckia nepalensis Hook. mediates antihyperglycemic activity in CC1 hepatocytes and in diabetic Wistar rats via regulating AMPK/G6Pase/PEPCK signaling axis

Ethnopharmacological relevanceOsbeckia nepalensis Hook. f. is an ICMR documented plant well known for its antidiabetic uses among the folk people of Northeast Region of India. In-depth study with scientific substantiation of the plant may uphold the therapeutic potential against the treatment of type 2 diabetes mellitus (T2DM). Aim of the studyThe present study evaluates the traditionally claimed prophylactic potential of O. nepalensis and its extracts along with the isolated compound taxifolin-3-O-glucoside (TG) against the downregulation of T2DM related hepatic gluconeogenesis through in vitro, in vivo and in silico conditions as a means of ameliorating hyperglycemia. Materials and methodsAntidiabetic potential of O. nepalensis was carried out in both CC1 hepatocytes (in vitro) and STZ-induced diabetic male Wistar rats (in vivo). Enriched bioactive fraction and bioactive molecules were isolated through bioactivity-guided fractionation, yielding two major molecules, taxifolin-3-O-glucoside and quercitin-3-O-rhamnoside. The bioactivity of taxifolin-3-O-glucoside was validated through immunoblotting techniques aided by in silico molecular docking and simulations. ResultsMethanolic extract of O. nepalensis and taxifolin-3-O-glucoside (TG) isolated thereof enhanced the uptake of glucose in CC1 hepatocytes and downregulates the gluconeogenic enzymes (G6Pase and PEPCK) and its related transcription factors (FOXO1, HNF4α and PGC1α) through the stimulation of AMPK phosphorylation in in vitro condition. Moreover, in in vivo experiments, the in vitro most active fraction BuSFr1 (consisting of the two active major compounds taxifolin-3-O-glucoside and quercitin-3-O-rhamnoside) exhibited a substantial decrease in elevated blood glucose level and increase the glucose tolerance as well as plasma insulin level. In silico molecular docking and simulations for TG with the protein G6Pase inferred the docking sites and stability and showed taxifolin-3-O-glucoside as more potent and non-toxic as compared to quercitin-3-O-rhamnoside. ConclusionThe traditionally claimed antidiabetic effect of O. nepalensis has been proved to be effective in lowering the blood glucose level through in vitro, in vivo and in silico analysis which will pave a way for the development of antidiabetic phytopharmaceutical drugs which can be validated through further clinical studies.

Glycemic indices and effect of bitter leaf (Vernonia amygdalina) flavored non-alcoholic wheat beer (NAWB) on key carbohydrate metabolizing enzymes in high fat diet fed (HFD)/STZ-induced diabetic Wistar rats.

In a bid to make the use of functional food easier in the management and prevention of diseases, product development and fortification from/with functional foods have become the recent focus of research. This study, therefore, sought to exploit the recent trend in the brewing industry on the production of non-alcoholic beers by investigating the possibility of having a non-alcoholic beer flavored with bitter leaf, a known plant widely reported to have a strong hypoglycemic effect, as against the traditional use of hops, and the effect of the produced beer on the glycemic indices and various diabetic biochemical parameters that serve as biomarkers for type-2 diabetes (T2D). The glycemic indices, as well as the inhibitory potentials of bitter leaf-flavored Non-alcoholic wheat beer (NAWB) in ratios of 100%HP, 100%BL, 75:25BL, 50:50BL, and 25:75BL, on enzymes linked to a high-fat diet/streptozocin (HFD/STZ)-induced T2D albino Wistar rats were investigated. There were no significant difference (p > .05) between the starch (1.72-1.77 mg/100 mL), amylose (0.22-0.24 mg/100 mL), and amylopectin (1.49-1.53 mg/100 mL) contents of the various samples. The Glycemic Index (GI) of the samples ranged from 36 to 73 with 75:25Bl and 50:50BL have the lowest (36) values. The samples reduced blood glucose levels and inhibited pancreatic α-amylase, lipase, and intestinal α-glucosidase activity. The inhibitory potentials of these beer samples on α-amylase and α-glucosidase as well as their ability to reduce blood glucose levels in diabetic rats thus making the bitter leaf flavored NAWB a suitable healthy beverage for better glycemic control in diabetics. PRACTICAL APPLICATIONS: This study revealed the potential of producing non-alcoholic wheat beer flavored with bitter leaves as a possible substitute for hops. The potential inherent in bitter leaf in the management of type 2 diabetes can thus be made available through a far-reaching beverage medium such as non-alcoholic beer to help in the treatment/management of T2D. The results of this research could be an eye-opener to the possible utilization of bitter leaf and by extension other plants that have been reported in the management of T2D. The use of the bitter leaf as a substitute for hops in the production of non-alcoholic beer in the brewing industry could help in a health-oriented campaign for safe drinks that could be helpful in the control of blood glucose levels of diabetic patients.

Lactobacillus-fermented yogurt exerts hypoglycemic, hypocholesterolemic, and anti-inflammatory activities in STZ-induced diabetic Wistar rats

Hyperglycemia is a symptom of type 2 diabetes mellitus, a chronic metabolic disease characterized by elevated blood glucose concentrations. Antidiabetic drugs are common treatments for this metabolic disorder; however, they may have unpleasant side effects. This study hypothesized that probiotic fermented products could preserve nutritional value, maintain metabolic homeostasis, and attenuate the inflammatory response associated with diabetes while reducing side effects. Lactobacillus plantarum KU985438 and Lactobacillus rhamnosus KU985439 showed the lowest alfa-amylase enzyme (α-amylase) activity among 8 lactobacilli tested. These 2 strains were used to develop functional fermented milk products, and their antidiabetic efficacy was tested in induced diabetic Wistar rats. The treatment of diabetic rats with L. plantarum KU985438 or L. rhamnosus KU985439 fermented yogurt resulted in a considerable reduction in blood glucose concentrations (136.79% and 145.17%, respectively) and α-amylase concentrations (56.84% and 56.84%, respectively) compared with conventional treatments. Diabetes relief began after 4 days of yogurt consumption compared with drug-based treatment. Significant improvements in both liver and kidney enzyme concentrations were also observed, in addition to a significant increase in high-density lipoprotein cholesterol concentrations and improved lipid profiles. Inhibition in nuclear factor κB and an increase in Bcl-2 concentrations were also detected. Histopathological examination of both hepatic and pancreatic cells revealed the positive effects of the studied treatment compared with standard treatment. Therefore, the selected Lactobacilli, which has hypoglycemic potential, could be used to produce functional nutraceutical antidiabetic supplements.

Multi target interactions of essential oil nanoemulsion of Cinnamomum travancoricum against diabetes mellitus via in vitro, in vivo and in silico approaches

This study reports antidiabetic activity of leaf essential oil (EO) of Cinnamomum travancoricum from the Western Ghats, India via in vitro , in vivo and in silico methods. EO was characterized by GC-MS and GC-FID. Essential oil nanoemulsions (EN) were prepared and characterized. Antidiabetic potential was evaluated through in vitro assays namely, α-amylase and α-glucosidase inhibition, glucose uptake and insulin secretion assays. In vivo study was conducted on STZ-induced diabetic Wistar rats. Molecular docking was conducted to find the lead antidiabetic compounds. Of the 42 compounds identified in the EO, α-phellandrene (5.9%), β-phellandrene (12.6%), linalool (23.6%), safrole (6.8%) and shyobunol (5.1%) were major constituents. Of the two ENs formulated, 1:2 ratio (EO to surfactants) was better in zeta size (51.4 nm) and potential (−30.9). In vitro results were impressive. EN lowered elevated blood glucose level to normal (p < 0.01) and improved the insulin secretion (p < 0.01) in diabetic rats. Further, serum AST, ALT, ALP, triglyceride and pancreatic β-cell damage were seen reduced (p < 0.05). Molecular docking studies showed minor constituents of EO, namely, δ-cadinene, elemol, spathulenol and α-copaen-11-ol playing active role in antidiabetic activity through α-amylase, α-glucosidase, insulin receptor, and insulin secretion proteins.

Synergistic effects of high-intensity interval training (HIIT) and intake of nettle on serum levels of chemerin and beta cells function in type 2 diabetic rats.

This animal study aimed to demonstrate the synergistic effect of high-intensity interval training (HIIT) and alcoholic extract of nettle on serum chemerin and beta cells function in type 2 diabetic male rats. Thirty-two STZ-induced diabetic male Wistar rats were randomly divided into four groups including the control group, the supplemented group with 200mg/day of nettle, the training group with five sessions per week of HIIT, and the group with combined nettle and HITT intervention. Body weight, lipid profile, beta cells function, and chemerin level were assessed after eight weeks of the intervention. The values of chemerin significantly decreased in combined HIIT and nettle intervention group compared to the control group (p=0.001). The levels of glucose and insulin decreased significantly in nettle group, exercise group, and combined HIIT and nettle group (p=0.001). The present study found that intense interval exercise with the consumption of alcoholic extract of nettle can affect the performance of beta cells, glucose, and insulin. Future human studies are warranted.

Anti-Diabetic Effect of Methanolic Extract of Aristolochia ringensLeaf

The aim and objective of this study is to investigate the hypoglycemic, hepatoprotective, hypolipidemic and antioxidant potentials of the methanolic extract of Aristolochia ringens leaf (MLAR) in STZ-induced diabetic wistar rats. The airdried and powdered leaf of the plant (Aristolochia ringens) was extracted by cold maceration and concentrated. In vitro analysis was carried out by screening the extract for phytochemical constituents and antioxidant activities using different models. In vivo analysis was also carried out by randomly dividing forty eight (48) male wistar rats (140-170 g) into eight groups of six (6) rats each. Group 1 served as control; group 2 received STZ (60 mg/kg wt i.p); groups 3 to 8 served as the treatment group. The animals were sacrificed without anesthesia after 30 days and their blood were collected for biochemical investigation. The in vitro results showed that MLAR possesses good antioxidant potential when compared with the standard and it is also known to contain a number of phytochemicals. Also, the administration of STZ caused significant (p<0.05) elevation of the serum level of glucose, ALT AST, GGT, ALP, total cholesterol, LDL, TRIGS, MDA, NO and MPO activity by 100%, 47%, 38%, 32%, 51%, 29%, 34%, 41%, 51%, 29%, 54% and 59% respectively and significant reduction in HDL, Catalase, GPx, GSH, SOD, GST and plasma insulin by 34%, 34%, 61%, 46%, 66%, 55% and 52% respectively, but supplementation with MLAR brought all these parameters close to normal. In conclusion, Aristolochia ringens may be used as a prophylactic and an alternative medicine in the treatment of diabetes mellitus as it was established in this study that it possesses antioxidant, antiinflammatory, hypolipidemic and hypoglycemic effects which may be due to the presence of phytochemicals in it.

Investigating the effect of some fluoroquinolones on C-reactive protein levels and ACh-Induced blood pressure reduction deviations after aging of diabetes in STZ-Induced diabetic wistar rats

The treatment of infections in diabetic patients by fluoroquinolone antibiotics is associated with a reduced risk of coronary artery disease, and may improve endothelium-derived hyperpolarizing factor (EDHF) efficacy. The inflammatory marker C-reactive protein (CRP) is an important predictor of cardiovascular events, and vascular endothelium dysfunction, which makes this marker a target for drug-based treatment. This study aims to investigate the relation between the treatment by fluoroquinolones with CRP plasma levels, as well as acetylecholine (ACh)-induced small conductance calcium-activated potassium channels (SKCa)-dependent blood pressure (BP) reduction deviations in wistar rats after inducing a type 2-like diabetes with aging state after four months of streptozotocin (STZ) injection. Experimental animals were divided into four groups, group 1: diabetic animals were treated with moxifloxacin (n = 15), group 2: diabetic animals were treated with levofloxacin (n = 15), group 3: diabetic control animals (n = 15), and group 4: non-diabetic control animals (n = 6). The levels of plasma CRP, as well as ACh-induced SKCa-dependent BP reduction deviations were compared four months after the development of diabetes, after that; two groups were treated with fluoroquinolones, four months after the treatment; CRP-plasma levels, as well as ACh-induced SKCa-dependent BP reduction deviations were also evaluated and compared for all groups. Sustained hyperglycemia after the induction of diabetes elevated CRP plasma levels, and reduced ACh-induced SKCa-dependent BP reduction, observed diabetes-induced variations were minimal in fluoroquinolones treated diabetic groups compared with diabetic control group, In conclusion, the treatment with fluoroquinolone antibiotics in diabetic wistars may be associated with a lowering in CRP levels progression, and improvement in SKCa vitality, which indicates the importance of treating infections in diabetics by fluoroquinolones to mitigate some vascular complications signs that lead to morbidity and mortality in diabetes.

Antioxidant and Antihyperlipidemic Activity of Methanolic Fraction of Maytenus heyneana Root on STZ Induced Diabetic Wistar Rats

Antioxidant and Antihyperlipidemic Activity of Methanolic Fraction of Maytenus heyneana Root on STZ Induced Diabetic Wistar Rats

Investigating the effect of some fluoroquinolones on blood glucose and insulin levels in STZ-induced diabetic wistar rats

Fluoroquinolone antibiotics may cause acute disorders in blood glucose levels, this side effect is worthwhile, especially in diabetic patients, this study aimed to investigate the effect of each of two fluoroquinolones, moxifloxacin and levofloxacin, on blood glucose levels in STZ-induced diabetic wistar rats after induction of a type 2-like diabetes, and ensuring the stability of the diabetic condition, as well as waiting for aging (4 months). Experimental animals were divided into four groups: group 1; diabetic animals were treated with moxifloxacin (n=15), group 2; diabetic animals were treated with levofloxacin (n=15), group 3; diabetic control animals (n=15), and group 4; non-diabetic control animals (n=6), insulin levels, body weights, and blood glucose levels were compared at different times for a period of 14 days during the treatment with fluoroquinolones. Fluoroquinolones reduced blood glucose levels, this effect was greater with levofloxacin than moxifloxacin, accompanied with high insulin levels with levofloxacin more than moxifloxacin. There were no statistically significant differences in body weights after treating with fluoroquinolones, in conclusion: there are dissimilarity in the effect of moxifloxacin and levofloxacin on blood glucose and Insulin levels in type-2 diabetes, inspite of the importance of these compounds in the treatment of resistant infections on other antibiotics, it is necessary to exercise caution when using these compounds in diabetic patients through the precautional monitoring of blood glucose levels.

Antioxidant, anti-inflammatory and anticholinergic action of berberine attenuates diabetic encephalopathy: Behavioral and biochemical evidences

Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, involves direct neuronal damage caused by intracellular glucose. The present study was designed to investigate the effect of berberine an anti-oxidant and anti-inflammatory molecule, on cognitive functions, oxidative-nitrosative stress and inflammation in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic Wistar rats were treated with berberine for 6 weeks at 50 and 100 mg/kg/day. During fifth week of treatment, learning and memory was investigated in single Y-maze and passive avoidance test. At the end of the study biochemical parameters like acetylcholinesterase (AchE) activity, nitrite levels, tumor necrosis factor-alpha (TNF-α) and oxidative stress was measured from cerebral cortex and hippocampus regions of brain. AchE activity was found increased by 56 % in the cerebral cortex of diabetic rat brain. Lipid peroxidation (LPO) levels were increased by 100 % and 95 % in cerebral cortex and hippocampus of diabetic rats, respectively. Nonprotein thiol levels, enzymatic activities of superoxide dismutase and catalase were found decreased in cerebral cortex and hippocampal regions of diabetic rat brain. Nitrite levels in both regions of diabetic brain were increased significantly (P < 0.05) compared to control group. TNF-α, a pro-inflammatory cytokine, was found significantly increased in diabetic rats. Conversely, animal groups treated with significantly attenuated these behavioral and biochemical abnormalities. The results suggest a protective role of berberine against diabetic encephalopathy, which may be sum of its anti-oxidant, anti-cholinesterase, anti-inflammatory and glucose lowering action.

Methanol-Extract/Fractions of Dacryodes edulis Leaves Ameliorate Hyperglycemia and Associated Oxidative Stress in Streptozotocin-Induced Diabetic Wistar Rats.

The present study evaluated the antidiabetic and antioxidant potential of the methanolic extract/solvent fractions of the leaves of Dacryodes edulis using a streptozotocin (STZ)-induced diabetic Albino Wistar rat model. The fasting blood glucose/insulin levels and inhibition of α-amylase and α-glucosidase were determined. Antioxidant activity was assessed in vitro by 2,2-diphenyl-1-picrylhydrazyl, hydroxyl, superoxide scavenging, reducing power, and total antioxidant capacity assays and in vivo by monitoring catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and reduced glutathione (GSH) and malondialdehyde (MDA) levels. The aqueous-methanol fraction exhibited the highest and significant (P < .05) reduction in fasting blood glucose (FBG; 54.03%) with a concomitant inhibition of α-amylase and α-glucosidase activities. The ethyl acetate fraction also exhibited a significant (P < .05) reduction in FBG and an increase in insulin levels in the treated diabetic Wistar rats. A significantly (P < .05) higher reducing power and radical scavenging activity was observed in the aqueous-methanol and ethyl acetate fractions. The aqueous-methanol and ethyl acetate fractions also significantly (P < .05) reversed the alterations in oxidative stress markers (GSH, MDA, CAT, and SOD) observed in the diabetic control group. In conclusion, the study demonstrated that the methanol extract of Dacryodes edulis ameliorates hyperglycemia and the associated oxidative stress in STZ-induced diabetic Wistar rats. These observed activities are largely due to the compounds that partitions into the aqueous-methanol (55:45) solvent fraction. This provides scientific evidence for the use of this plant extract in folk medicine and also a baseline data for its further characterization. Further work should be carried out to characterize the aqueous-methanol solvent fractions for the active compounds.

Taurine ameliorates oxidative stress induced inflammation and ER stress mediated testicular damage in STZ-induced diabetic Wistar rats

One of the major consequences of diabetes is reproductive dysfunction but the fundamental mechanisms are still poorly known. The objective of the present study was to explore the beneficial role of taurine against streptozotocin induced testicular dysfunctions in diabetic male Wister rats and understanding the underlying intricate molecular mechanisms. Exposure to streptozotocin (50 mg kg−1 body weight, i.p., once) elevated blood glucose level, induced testicular histological alterations and reduced testis-to-body weight ratio, serum testosterone, testicular markers and activity of antioxidant enzymes. Generation of ER stress (increased expression of calpain-1, caspase-12 and upregulation of CHOP, GRP78 via eIF2α signaling), translocation of NF κB in the nucleus (leading to the upregulation in the levels of inflammatory cytokines), activation of mitochondria dependent apoptotic pathway and DNA fragmentation were revealed from this study. However, administration of taurine at a dose of 100 mg kg−1 body weight for 6 weeks post diabetic induction, successfully ameliorated all these adverse effects. Thus, taurine, as a potential therapeutic agent, may hold promise in preventing oxidative and ER stress mediated diabetic testicular complications in rats.

English

The purpose of this study is to evaluate the capacity of lycopene against diabetes-induced oxidative damage in Wistar rats. Thirty Wistar rats of both sexes, twenty-five of which were diabetic, were used. Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ) 60 mg/kg body weight and it was confirmed by the elevated blood glucose ≥200 mg/dl after three days. The rats were divided randomly into groups 1 to 6, each containing 5 rats. Group 1 (Normal control) and Group 2 (Diabetic control) rats were administered 0.5 ml of olive oil; Groups 3, 4, and 5 rats were, respectively, administered 10, 20, and 40 mg/kg body weight of lycopene, while Group 6 rats were administered 2 mg/kg body weight of Glibenclamide. All administrations were done orally and once daily for twenty-eight days. At the end of the treatment, serum levels of antioxidant enzymes, cortisol and malondialdehyde (MDA) were determined. Administration of graded doses of lycopene to diabetic animals significantly (P<0.05) decreased the blood glucose concentration after four weeks of treatment when compared to diabetic untreated animals. Serum levels of cortisol and MDA (index of oxidative stress) were reduced while there were up-regulated activities of serum endogenous enzymes (superoxide dismutase, catalase and glutathione peroxidase) in diabetic animals treated with all doses of lycopene when compared with diabetic untreated animals. Overall, lycopene attenuated the biomedical alterations in STZ-induced diabetic Wistar rats. Lycopene therefore possesses antioxidant activity at the doses tested in this study. Key words: Lycopene, diabetes mellitus, oxidative stress, cortisol, malondialdehyde, catalase, glutathione peroxidase.

Effects of acetone extract of Cola nitida on brain sodium-potassium adenosine triphosphatase activity and spatial memory in healthy and streptozotocin-induced diabetic female Wistar rats.

Background This study was carried out to investigate the effects of acetone extract of Cola nitida on brain Na+/K+-ATPase activity and spatial memory of healthy and streptozotocin (STZ)-induced diabetic female Wistar rats. Methods Forty-two female Wistar rats were used for this study and were randomly distributed into six groups (n=7). Rats in group 1 were used as control and were administered normal saline; group 2 rats were healthy rats administered 50 mg/kg of kola nut extract per day; group 3 rats were healthy rats administered 100 mg/kg of kola nut extract per day; group 4 rats were a diabetic group also administered normal saline; group 5 rats were diabetic rats administered 50 mg/kg of kola nut extract per day; and group 6 rats were diabetic rats administered 100 mg/kg of kola nut extract per day. Diabetes was induced with 50 mg/kg of STZ. After 3 weeks of administration, the spatial memories of the rats were tested using the Y-maze, followed by assay of Na+/K+-ATPase activity. Results The result shows a significant increase in Na+/K+-ATPase activity of diabetic treated groups (5 and 6) when compared with the diabetic group (4) and a significant increase in Na+/K+-ATPase activity of healthy treated groups (2 and 3) when compared with control. Also, there was a significant increase in spatial memory of the diabetic treated groups when compared with diabetic group. Conclusions This study revealed that kola nut extract has restorative effect on brain Na+/K+-ATPase activities and spatial memory of STZ-induced diabetic female Wistar rats.

Black Seed Thymoquinone Improved Insulin Secretion, Hepatic Glycogen Storage, and Oxidative Stress in Streptozotocin-Induced Diabetic Male Wistar Rats.

Diabetes mellitus is one of the metabolic diseases having several complications. Nigella sativa oil (NSO) might have beneficial effects in the treatment of diabetic complications. Thirty-two mature male Wistar rats were equally divided into four experimental groups: control, control NSO 2 mL/kg, streptozotocin- (STZ-) induced diabetic, and diabetic (STZ-induced) treated with oral NSO 2 mg/kg for 30 days. Fasting blood glucose (FBG), insulin, and lipid profile levels were determined. Pancreatic and hepatic tissues were used for catalase and GSH. Histopathology, hepatic glycogen contents, insulin immunohistochemistry, and pancreatic islet morphometry were performed. NSO 2 mL/kg was noticed to decrease (P < 0.05) FBG and increase (P < 0.05) insulin levels in diabetic rats than in diabetic nontreated animals. Lipid profile showed significant (P < 0.5) improvement in diabetic rats that received NSO 2 mL/kg than in the diabetic group. Both pancreatic and hepatic catalase and GSH activities revealed a significant (P < 0.05) increment in the diabetic group treated with NSO than in the diabetic animals. NSO improved the histopathological picture and hepatic glycogen contents of the diabetic group as well as increased (P < 0.05) insulin immunoreactive parts % and mean pancreatic islet diameter. NSO exerts ameliorative and therapeutic effects on the STZ-induced diabetic male Wistar rats.

Effects of Medium Chain Triacylglycerols on the Pathological Condition and Energy Bioavailability of Streptozotocin-induced Diabetic Rats.

Diabetes is a disease characterized not only by a high blood glucose level but also by high ketone levels. Medium chain triacylglycerols (MCT) are known as functional lipids, but they are rapidly metabolized to produce ketone bodies. In this study, we examined the effects of MCT intake on the pathological condition and energy bioavailability of diabetic animals. Streptozotocin (STZ)-induced diabetic rats were used as animal models for type I diabetes. The pathological condition was estimated through blood biochemical values, and the energy expenditure was calculated based on the respiratory quotient, which was analyzed using a mass spectrometer.Eight-week-old male STZ-induced diabetic Wistar rats were prepared and fed soybean oil (LCT) or MCT diets for 60 days. The survival rate of rats fed the MCT diet was higher than that of rats fed the LCT diet, although no ameliorating effects in the blood biochemical values were observed. In rats fed the LCT diet, their energy expenditure was much higher than their energy intake, whereas the energy balance was approximately equal in rats fed the MCT diet.These results indicated that energy bioavailability may contribute, at least in part, to the high survival rates in the diabetic MCT group, although MCT intake did not definitely improve the pathological condition of the experimental rats.

Sapium ellipticum (Hochst) Pax ethanol leaf extract modulates glucokinase and glucose-6–phosphatase activities in streptozotocin induced diabetic rats

Abstract Objective To examine the effects of Sapium ellipticum (SE) leaf extract on the hepatic activities of glucokinase and glucose-6-phosphatase in streptozotocin-induced diabetic Wistar rats. Methods STZ-induced diabetic Wistar rats (four groups, n = 8) were used in this study. SE was assessed at two different doses, 400 and 800 mg/kg BW, in comparison with metformin (METF) (12 mg/kg BW) as a reference antidiabetic drug. All treatments were done orally (p.o), twice daily at 8 h interval for a period of 21 days. Glucokinase and glucose-6-phosphatase activities were respectively determined using standard protocols. Hepatic and muscle glycogen contents were estimated as well. Results STZ caused significant decrease in glucose-6-phosphatase activity and concomitant increase in glucokinase activity. SE extract especially at 400 mg dosage significantly reversed the alterations by increasing glucokinase activity by 40.31% and inhibiting glucose-6-phosphatase activity by 37.29% compared to diabetic control animals. However, the effects were significantly lower than that of METF which enhanced glucokinase activity by 94.76% and simultaneously inhibited glucose-6-phosphatase activity by 49.15%. The extract also improved hepatic glycogen level by 32.37 and 27.06% at 400 and 800 mg dosage respectively. HPLC-MS analysis of some SE fractions in dynamic MRM mode (using the optimized compound-specific parameters) revealed among other active compounds, the presence of amentoflavone, which has been associated with antidiabetic function. Conclusions The ability of SE extract to concurrently inhibit glucose-6-phosphatase and activate glucokinase in this study suggests that it may be a treatment option for type 2 diabetes patients, and the presence of amentoflavone in the plant extract may account for its anti-diabetic potential.