Antioxidant and anti-inflammatory effects of Boswellia dalzielii and Hibiscus sabdariffa extracts in alloxan-induced diabetic rats.

Diabetes mellitus (DM) is one of the leading worldwide public health problems. It is characterized by hyperglycemia which induces oxidative stress and inflammation, both involved in the pathogenesis of diabetes. We previously showed that Boswellia dalzielii (BD) and Hibiscus sabdariffa (HS) extracts reduced hyperglycemia and hyperlipidemia in alloxan-induced diabetic rats. In the present study, we evaluated the antioxidant and anti-inflammatory activities of both plants in alloxan-induced diabetic rats. Two sets of experiments were conducted in male Wistar rats subjected to a single intraperitoneal injection of alloxan monohydrate (150 mg/kg, b. w.). Then, diabetic rats were daily administered with either BD (1st set of experiments) or HS (2nd set of experiments) at 100, 200, and 400 mg/kg orally for 21 consecutive days. Glibenclamide (10 mg/kg) was also administered as a reference drug. At the end of the study, the animals were anesthetized, and blood samples were collected from each animal. Then, oxidative stress and inflammatory biomarkers in the serum were determined. We found that treatment with BD and HS significantly reduced malondialdehyde (MDA) and enhanced the levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). These extracts also significantly decreased the inflammatory markers tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1ß). From the results obtained, it can therefore be concluded that BD and HS have the potential to being developed as natural sources of antioxidant and anti-inflammatory agents that can be used for the prevention or treatment of DM.

Pancreatic regenerative potential of manuka honey evidenced through pancreatic histology and levels of transcription factors in diabetic rat model.

Background: Diabetes mellitus is a commonly occurring metabolic disorder accompanied by high morbidity and alarming mortality. Besides various available therapies, induction of pancreatic regeneration has emerged as a promising strategy for alleviating the damaging effect of diabetes. Honey, a potent antioxidative and anti-inflammatory agent, has been reported in the literature archive to exhibit favourable results in the regeneration process of several organ systems. Design: The current research work was intended to explore the potential role of manuka honey in pancreatic regeneration in alloxan-induced diabetic rats by accessing the pancreatic histology and levels of relevant transcription factors, including MAFA, PDX-1, INS-1, INS-2, NEUROG3, NKX6-1, and NEUROD. An equal number of rats were allocated to all four experimental groups: normal, negative control, positive control, and treatment group. Diabetes was induced in all groups except normal through a single intraperitoneal dose of alloxan monohydrate. No subsequent treatment was given to the negative control group, while the positive control and treatment groups were supplemented with metformin (150 mg/kg/day) and manuka honey (3 g/kg/day), respectively. Results: Statistical comparison of glucose and insulin levels, oxidative stress indicators, changes in the architecture of pancreatic islets, and expression levels of regeneration-associated transcription factors advocated the potential role of manuka honey in ameliorating the alloxan-induced hyperglycaemia, hyperinsulinemia, oxidative stress, and necrotic changes in islets along with significant upregulation of relevant transcription factors. Conclusion: This suggests to us the auspicious role of antioxidants in honey in pancreatic regeneration and advocates the favourable role of manuka honey in combating diabetes mellitus.

CARBOHYDRATES METABOLISM IN THE BLOOD OF RATS WITH IMPAIRED GLUCOSE TOLERANCE UNDER LONG TERM MELATONIN INJECTIONS.

OBJECTIVE: The aim: To determine the influence of melatonin on the glucose level and content of malondialdehyde, activities of pyruvate kinase and glucose-6-phosphate dehydrogenase enzymes in the blood; histochemical features of glycogen distribution in liver of rats with impaired glucose tolerance. PATIENTS AND METHODS: Materials and methods: Diabetes in rats was induced by intra-abdominal injection of a 5% solution of alloxan monohydrate at the rate of 170 mg/kg of body weight. Four days after animals were divided into rats with impaired glucose tolerance and melatonin-group with impaired glucose tolerance (5 mg/ kg «Sigma¼ USA, daily and intraperitoneal for 42 days starting from 5th day). Impaired glucose tolerance was determined by measurement of glucose profiles - fasting <5.6 mmol/l; postprandial (2h post-load) 7.8 - 11.0 mmol/l. Histochemical examination of the liver was performed according to the standard method of PAS-reaction staining. Statistical analysis was performed using Statistica 10 StatSoft Inc. RESULTS: Results: Pyruvate kinase activity in erythrocytes and optical density of glycogen in hepatocytes of animals with impaired glucose tolerance decreased on 18% and 11%, activity of glucose-6-phosphate dehydrogenase and content of malondialdehyde increased on 35% and 23%, respectively compared with the control. We have reached the recovery of the pyruvate kinase and normalization of glucose-6-phosphate dehydrogenase activities, malondialdehyde levels, glucose profiles in the blood as well as glycogen distribution in the liver caused by melatonin injections. CONCLUSION: Conclusions: We have determined that long term melatonin injections did better glucose tolerance in rats.

Morroniside interaction with poly (ADP-ribose) polymerase accentuates metabolic mitigation of alloxan-induced genotoxicity and hyperglycaemia: a molecular docking based in vitro and in vivo experimental therapeutic insight.

The present study tends to evaluate the possible potential of bio-active Morroniside (MOR), against alloxan (ALX)-induced genotoxicity and hyperglycaemia. In silico prediction revealed the interaction of MOR with Poly (ADP-ribose) polymerase (PARP) protein which corroborated well with experimental in vitro L6 cell line and in vivo mice models. Data revealed the efficacy of MOR in the selective activation of PARP protein and modulating other stress proteins NF-κB, and TNF-α to initiate protective potential against ALX-induced genotoxicity and hyperglycaemia. Further, the strong interaction of MOR with CT-DNA (calf thymus DNA) analyzed through CD spectroscopy, UV-Vis study and ITC data revealed the concerted action of bio-factors involved in inhibiting chromosomal aberration and micronucleus formation associated with DNA damage. Finally, MOR does not play any role in microbial growth inhibition which often occurs due to hyperglycemic dysbiosis. Thus, from the overall findings, we may conclude that MOR could be a potential drug candidate for the therapeutic management of induced-hyperglycaemia and genotoxicity.Communicated by Ramaswamy H. Sarma.

Phenolics Extracted from Jasminum sambac Mitigates Diabetic Cardiomyopathy by Modulating Oxidative Stress, Apoptotic Mediators and the Nfr-2/HO-1 Pathway in Alloxan-Induced Diabetic Rats.

Diabetes mellitus is a chronic metabolic disorder defined as hyperglycemia and pancreatic ß-cell deterioration, leading to other complications such as cardiomyopathy. The current study assessed the therapeutic effects of phenolic acids extracted from Jasminum sambac phenols of leaves (JSP) against diabetes-induced cardiomyopathy in rats. The rats were divided into four groups, with each group consisting of 20 rats. The rats were given intraperitoneal injections of alloxan monohydrate (150 mg/kg) to induce diabetes. The diabetes-induced groups (III and IV) received treatment for six weeks that included 250 and 500 mg/kg of JSP extract, respectively. In the treated rats, the results demonstrated that JSP extract restored fasting glucose, serum glucose, and hyperlipidemia. Alloxan induced cardiomyopathy, promoted oxidative stress, and altered cardiac function biomarkers, including cardiac troponin I, proBNP, CK-MB, LDH, and IMA. The JSP extract-treated rats showed improved cardiac function indicators, apoptosis, and oxidative stress. In diabetic rats, the mRNA expression of caspase-3, BAX, and Bcl-2 was significantly higher, while Bcl-2, Nrf-2, and HO-,1 was significantly lower. In the treated groups, the expression levels of the BAX, Nrf-2, HO-1, Caspase-3, and Bcl-2 genes were dramatically returned to normal level. According to our findings, the JSP extract prevented cardiomyopathy and heart failure in the hyperglycemic rats by improving cardiac biomarkers and lowering the levels of hyperlipidemia, oxidative stress, apoptosis, hyperglycemia, and hyperlipidemia.

Effect of heterologous platelet-rich plasma on liver and modulation of glucose metabolism and Wnt signalling pathways in diabetic mice.

BACKGROUND: The current study was designed to highlight the effects of heterologous platelet-rich plasma (PRP) on deteriorated hepatic tissues and impaired glucose metabolism of alloxan-induced diabetic mice. METHODS: 30 male mice were divided into a control (CG), PRP (PG), diabetic (DG), and two treated groups (T1G and T2G). PG was given PRP treatment (0.5 ml/kg body weight) twice a week for four weeks. DG, T1G and T2G were given alloxan (150 mg/kg) to induce diabetes. After confirmation, PRP treatment was given to T1G and T2G for two and four weeks respectively while DG was left untreated. Upon completion of the said experimental period, liver samples were taken for histological and gene expression analyses. RESULTS: The study found that the liver tissue of the DG group showed signs of damage, including hepatocyte ballooning, sinusoid dilatation, and collagen deposition. However, these changes were significantly reduced in both T1G and T2G groups. The expression of several genes related to liver function was also affected, with upregulation of Fbp1 and Pklr, and downregulation of Pck1 in the DG group. PRP treatment restored Fbp1 expression and also increased the expression of glycolytic pathway genes Hk1 and Gck, as well as Wnt signalling pathway genes Wnt2, Wnt4, and Wnt9a in both treated groups. CONCLUSION: Current study revealed that heterologous PRP may partly alleviate high glucose levels in diabetics possibly by mediating glucose metabolism via inhibition of Wnt signalling pathway.

The Effects of Metformin Treatment on Diabetic Albino Rats' Pancreas, Liver, and Kidney Histology.

Metformin, an oral hypoglycemic drug, has traditionally been considered the standard therapy for hyperglycemia. Metformin's several modes of action include inhibition of hepatic gluconeogenesis, anti-glucagon activity, and insulin-sensitizing effect. This study aims to assess the effectiveness of Metformin on the liver, pancreatic, and kidney tissues of alloxan-induced diabetic albino rats. Twenty mature albino white male rats were allocated at random into two groups. Intraperitoneal injections of alloxan monohydrate were utilised to induce diabetic Mellitus type II in the first ten rats. The second group of rats were injected intraperitoneally with normal saline. Both groups were then separated into four subgroups: Group 1 consisted of non-diabetic rats that were only administered distilled water (control), Group 2 consisted of non-diabetic rats that were administered metformin at a dose of 1000 mg/kg/day, and Group 3 consisted of diabetic control animals that were administered alloxan intravenously and distilled water orally, but were not given any medications. After seven days of DM induction, diabetic rats were administered Metformin at a dose of 1000 mg/kg/day orally. After one month of therapy, the animals were slaughtered and their organs were harvested. Compared to the control group, the histological results of pancreatic tissue were normal in the treatment groups. In contrast, liver and kidney sections from non-diabetic control, non-diabetic, and diabetic animals given 1000 mg/kg/day of Metformin had normal histology. Still, both tissues of untreated diabetic control mice exhibited lymphocyte infiltration. Metformin has been found to have significant blood glucose lowering properties and the capacity to protect several organs from the negative consequences of diabetes.

The effect of phytoprotectors on the functioning of liver NAD⁺- and NADP⁺-maliс enzymes in rats with alloxan diabetes.

The development of experimental alloxan diabetes in rats was accompanied by the increase the activity of liver NAD⁺- and NADP⁺-dependent malic enzymes (ME; NAD⁺-ME, EC 1.1.1.39 and NADP⁺-ME, 1.1.1.40) associated with an increase in the rate of transcription of genes encoding these enzymes. Oral administration of aqueous extracts of Jerusalem artichoke and olive to diabetic rats caused a noticeable decrease in blood glucose, a decrease in the rate of transcription of the studied genes; and a decrease in ME activity towards normal values. Thus, extracts of Jerusalem artichoke and olive can be used as additives to the standard therapy of diabetes mellitus.

Self-recovery in diabetic Sprague Dawley rats induced by intraperitoneal alloxan and streptozotocin.

Alloxan and streptozotocin are the most popular diabetogenic agents in assessing antidiabetic activity. Self-recovery, indicated by unstable hyperglycemia conditions in animals induced by those agents, becomes a significant disturbance to accurate examination. This study aimed to evaluate and reveal the self-recovery incidence in Sprague Dawley rats induced with alloxan and streptozotocin. Each dose of alloxan (120, 150, 180 mg/kg) and streptozotocin (40, 50, 60 mg/kg) was administered through intraperitoneal injection. The results showed that each dose of alloxan induced self-recovery incidence. In rats given streptozotocin, self-recovery only occurred at a dose of 40 mg/kg. The other higher doses of streptozotocin induced stable hyperglycemia. Furthermore, this study revealed two types of self-recovery, namely temporary recovery and end recovery. Temporary recovery occurred in rats given alloxan, during end recovery in alloxan and streptozotocin. The examination of insulin levels showed a significant reduction in the temporary recovery and stable diabetic rats compared to the end recovery rats. Besides, the bodyweight of rats was also affected by different incidences of self-recovery. This study recommends paying more attention to the possibility of self-recovery in obtaining animal models of diabetes, emphasizing the determination of suitable diabetogenic agents and proper doses to reduce self-recovery incidences. The finding of temporary recovery in rats receiving alloxan indicates that alloxan induced delayed diabetes in rats.

LC/MS analysis of mushrooms provided new insights into dietary management of diabetes mellitus in rats.

Mushrooms possess antihyperglycemic effect on diabetic individuals due to their nonfibrous and fibrous bioactive compounds. This study aimed to reveal the effect of different types of mushrooms on plasma glucose level and gut microbiota composition in diabetic individuals. The effects of five different mushroom species (Ganoderma lucidum, GLM; Pleurotus ostreatus, POM; Pleurotus citrinopileatus, PCM; Lentinus edodes, LEM; or Hypsizigus marmoreus, HMM) on alloxan-induced diabetic rats were investigated in this study. The results indicated that LEM and HMM treatments showed lower plasma glucose levels. For the microbiota composition, ACE, Chao1, Shannon, and Simpson were significantly affected by PCM and LEM treatments (p < .05), while ACE, Shannon, and Simpson indexes were affected by HMM treatment (p < .01). Simpson index was affected in positive control (C+) and POM groups. All these four indices were lower in GLM treatment (p < .05). Dietary supplementation of mushrooms reduced plasma glucose level directly through mushrooms' bioactive compounds (agmatine, sphingosine, pyridoxine, linolenic, and alanine) and indirectly through stachyose (oligosaccharide) and gut microbiota modulation. In conclusion, LEM and HMM can be used as food additives to improve plasma glucose level and gut microbiome composition in diabetic individuals.

Therapeutic Potential of Dillenia indica L. in Attenuating Hyperglycemia-Induced Oxidative Stress and Apoptosis in Alloxan-Administered Diabetic Mice.

BACKGROUND: Hyperglycemia-induced oxidative stress accelerates the process of apoptosis in tissues. Dilleniaindica (DI) is a medicinal plant, and its fruit contains many therapeutic properties. The therapeutic activity of the Methanolic Fruit Extract (MFE) of DI in attenuating oxidative stress and apoptosis in the liver and kidney tissues of alloxan-induced diabetic mice was analyzed in the present study. METHODS: High-Performance Thin Layer Chromatography (HPTLC) profiling of MFE was conducted. GLUT4 protein expression analysis and lipid peroxidation assays were conducted to check for MFE effect by administering in diabetic mice. An ultrastructural study was conducted for both the tissues. In apoptotic studies, the TUNEL assay and apoptotic protein expression analysis was conducted. RESULTS: High-Performance Thin Layer Chromatography (HPTLC) profiling of MFE showed the presence of two crucial antioxidants, ascorbic acid, and naringenin. In GLUT-4 protein expression analysis, MFE suppresses hyperglycemia by upregulating GLUT4 protein expression. Lipid peroxidation assay showed a decrease in malondialdehyde (MDA) upon MFE administration in diabetic mice. An ultrastructural study was conducted, and MFE was found to restore cellular alterations in diabetic tissues. In apoptotic studies, the TUNEL assay shows that MFE treatment showed fewer apoptotic cells than the diabetic group. The study also observed decreased caspase 3 protein expression and increased Bcl-2 protein expression. CONCLUSIONS: Therefore, it is inferred from the study that MFE can exert a protective effect by suppressing hyperglycemia and modulating oxidative stress and apoptosis in alloxan-administered diabetic mice.

Hypoglycaemic activity of biosynthesized copper oxide nanoparticles in alloxan-induced diabetic Wister rats.

BACKGROUND: Diabetes mellitus (DM) is a metabolic disorder that affects the body's ability to produce or use insulin. This study evaluated the hypoglycaemic activity of biosynthesized copper oxide nanoparticles (CuO-NPs) in alloxan-induced diabetic Wister rats. METHODS: CuO-NPs were synthesized via the green route and characterized using different analytical tools. Diabetes was induced intraperitoneally using 90 mg/kg body weight of alloxan monohydrate in albino rats. Thirty (30) rats were randomly divided into 5 groups of 6 rats each and orally treated for 21 days. Groups I and II were treated with 300 mg/kg bwt Cereus hildmannianus extract and CuO-NPs, respectively. Groups III and IV received 5 mg/kg bwt of Glibenclamide and 2 mL of normal saline, respectively, while Group V was left untreated as the diabetic control. Blood glucose (BG) levels and body weight changes were monitored at 3- and 7-day intervals, respectively, throughout 21-day treatment period. Lipid profiles, enzyme assays and histopathological studies of the liver were also carried out. RESULTS: Spheroidal tenorite phase of CuO-NPs with a crystallite size of 62.57 nm, surface area (20.64 m2 /g) and a UV-maximum absorption at 214.27 nm was formed. The diabetic rats treated with 300 mg/kg bwt CuO-NPs had the highest BG lowering ability (from 482.75 ± 27.70 to 124.50 ± 2.50 mg/dL). A significant difference (p < 0.05) in weight gain and serum enzymes was also observed in the CuO-NPs treated group compared with other groups. The CuO-NPs-treated group had a significant increase (p < 0.05) in HDL-cholesterol and a decrease in total cholesterol, triglycerides, LDL-cholesterol and VLDL-cholesterol compared with other groups. CONCLUSION: The green synthesized CuO-NPs nanoparticles significantly reduced (p < 0.05) blood glucose levels in rats and other associated indices and could serve as drug lead in the treatment of diabetes.

Determination of Hypoglycemic, Hypolipidemic and Nephroprotective Effects of Berberis Calliobotrys in Alloxan-Induced Diabetic Rats.

Many plants of the Berberis genus have been reported pharmacologically to possess anti-diabetic potential, and Berberis calliobotrys has been found to be an inhibitor of α-glucosidase, α-amylase and tyrosinase. Thus, this study investigated the hypoglycemic effects of Berberis calliobotrys methanol extract/fractions using in vitro and In vivo methods. Bovine serum albumin (BSA), BSA-methylglyoxal and BSA-glucose methods were used to assess anti-glycation activity in vitro, while in vivo hypoglycemic effects were determined by oral glucose tolerance test (OGTT). Moreover, the hypolipidemic and nephroprotective effects were studied and phenolics were detected using high performance liquid chromatography (HPLC). In vitro anti-glycation showed a significant reduction in glycated end-products formation at 1, 0.25 and 0.5 mg/mL. In vivo hypoglycemic effects were tested at 200, 400 and 600 mg/kg by measuring blood glucose, insulin, hemoglobin (Hb) and HbA1c. The synergistic effect of extract/fractions (600 mg/kg) with insulin exhibited a pronounced glucose reduction in alloxan diabetic rats. The oral glucose tolerance test (OGTT) demonstrated a decline in glucose concentration. Moreover, extract/fractions (600 mg/kg) exhibited an improved lipid profile, increased Hb, HbA1c levels and body weight for 30 days. Furthermore, diabetic animals significantly exhibited an upsurge in total protein, albumin and globulin levels, along with a significant improvement in urea and creatinine after extract/fractions administration for 42 days. Phytochemistry revealed alkaloids, tannins, glycosides, flavonoids, phenols, terpenoids and saponins. HPLC showed the presence of phenolics in ethyl acetate fraction that could be accountable for pharmacological actions. Therefore, it can be concluded that Berberis calliobotrys possesses strong hypoglycemic, hypolipidemic and nephroprotective effects, and could be a potential therapeutic agent for diabetes treatment.

Comparison of post-mortem vitreous fluid and blood glucose levels in diabetes-induced rabbit models.

Background: Diabetes is a common systemic disease in the world. Acute complications of diabetes may cause sudden unexpected deaths. Analysis done in vitreous fluid which is more protected and less contaminated by bacteria comparing to blood will produce more accurate results. Aim: Thus, we aimed to diagnose diabetes by comparing glucose levels of post mortem blood and vitreous fluid in death cases. Materials and Methods: A total of 17 New Zealand-type rabbits were divided into hyperglycemia (8), hypoglycemia (8), and control group (1). Rabbits were monitored for 5 days after experimental diabetes induction, and samples were taken at the point of death. Later rabbits were left in their environment, and samples were taken again at the post mortem first day. Mean blood glucose levels of hyperglycemia and hypoglycemia group were in diabetic range. Results: Blood glucose levels of hyperglycemic rabbits were measured as 512 ± 52,1 mg/dl, while vitreous glucose levels were 518,3 ± 76,8 mg/dl at the point of death. After one day, levels were measured as 433,9 ± 59,3 mg/dl and 329,8 ± 86,6 mg/dl. Blood glucose levels of hypoglycemic rabbits were measured as 39 ± 3,8 mg/dl, while vitreous glucose levels were 53,4 ± 13,9 mg/dl at the point of death. After one day, levels were measured as 36 ± 4,2 mg/dl and 1,6 ± 0,6 mg/dl. After analysis, there was a statistically significant difference between day 0 and 1 vitreous levels of hypoglycemia group. Conclusion: It can be clearly seen that vitreous fluid samples should be taken in judicial cases with sudden unexpected deaths like diabetes. This will contribute to identification cause of death.

Rodent Models of Diabetic Retinopathy as a Useful Research Tool to Study Neurovascular Cross-Talk.

Diabetes is a group of metabolic diseases leading to dysfunction of various organs, including ocular complications such as diabetic retinopathy (DR). Nowadays, DR treatments involve invasive options and are applied at the sight-threatening stages of DR. It is important to investigate noninvasive or pharmacological methods enabling the disease to be controlled at the early stage or to prevent ocular complications. Animal models are useful in DR laboratory practice, and this review is dedicated to them. The first part describes the characteristics of the most commonly used genetic rodent models in DR research. The second part focuses on the main chemically induced models. The authors pay particular attention to the streptozotocin model. Moreover, this section is enriched with practical aspects and contains the current protocols used in research in the last three years. Both parts include suggestions on which aspect of DR can be tested using a given model and the disadvantages of each model. Although animal models show huge variability, they are still an important and irreplaceable research tool. Note that the choice of a research model should be thoroughly considered and dependent on the aspect of the disease to be analyzed.

Ficus carica (Linn.) Leaf and Bud Extracts and Their Combination Attenuates Type-1 Diabetes and Its Complications via the Inhibition of Oxidative Stress.

The current work was designed to evaluate the antioxidant activity and antidiabetic effect of Ficus carica L. extracts. For that, the leaves and buds of Ficus carica L. were analyzed to determine their polyphenolic and flavonoid contents and antioxidant activity. Diabetes was induced by a single dose of alloxan monohydrate (65 mg/kg body weight), then diabetic rats were treated with a dose of 200 mg/kg body weight of the methanolic extracts of Ficus carica leaves or buds or their combination for 30 days. Throughout the experiment, blood sugar and body weight were measured every 5 and 7 days respectively. At the end of the experiment, serum and urine were collected for analysis of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, creatinine, uric acid, urea, proteins, sodium, potassium, and chloride. Pancreas, liver, and kidney were removed to estimate catalase, glutathione peroxidase, and glutathione activities; lipid peroxidation products were also determined. The results obtained revealed that alloxan has induced hyperglycemia, increased liver and renal biomarkers levels, reduced antioxidative enzymes, and induced lipid peroxidation. However, the treatment with Ficus carica leaf and bud extracts, especially their combination, has attenuated all pharmacological perturbations induced by alloxan.

Experimental Animal Models: Tools to Investigate Antidiabetic Activity.

About 2.8% of the global population are being suffered from Diabetes mellitus. Diabetes mellitus is a group of metabolic disorders that is characterized by an absolute lack of insulin and resulting in hyperglycemia. To overcome the challenges, many antidiabetic drugs are being used, and research is being carried out in search of more effective anti-diabetic drugs. To study the effectiveness of antidiabetic drugs, many diabetic models, chemicals, and diabetogenic hormones were used at the research level. In this review, we summarised various animal models used, chemicals that induce diabetes, their properties, and the mechanism of action of these models. Further, diabetes mellitus is generally induced in laboratory animals by several methods that include: chemical, surgical and genetic manipulations. To better understand both the pathogenesis and potential therapeutic agents, appropriate animal models of type 1 & type 2 diabetes mellitus are needed. However, for an animal model to have relevance to the study of diabetes, either the characteristics of the animal model should mirror the pathophysiology and natural history of diabetes or the model should develop complications of diabetes with an etiology similar to that of the human condition. There appears to be no single animal model that encompasses all of these characteristics, but there are many that provide very similar characteristics in one or more aspects of diabetes in humans. The use of the appropriate animal model based on these similarities can provide much-needed data on pathophysiological mechanisms operative in human diabetes.

Induction of Type I Diabetes Mellitus in Beagle Dogs Using Alloxan and Streptozotocin.

This article describes a protocol for chemically inducing type I diabetes mellitus in beagle dogs using a mixture of alloxan (ALX) and streptozotocin (STZ). ALX and STZ are both cytotoxic, diabetogenic agents that cause necrosis of pancreatic ß-cells and therefore halt the production of insulin. Although both compounds are widely used in experimental animal models of diabetes, standard protocols employing a single high dose of either agent are also implicated in adjacent organ damage. In contrast, combined administration of ALX and STZ allows for the use of lower doses, a method that effectively destroys ß-cells and circumvents unwanted adverse effects. The procedures described in this protocol produce persistent, insulin-dependent hyperglycemia in beagle dogs using combined doses of ALX and STZ lower than those previously described for a single intravenous administration. This model can be used to test experimental compounds indicated for the treatment of diabetes. © 2022 Wiley Periodicals LLC. Basic Protocol: Induction of type I diabetes mellitus in beagle dogs using alloxan and streptozotocin.

Chronically administered Agave americana var. marginata extract ameliorates diabetes mellitus, associated behavioral comorbidities and biochemical parameters in alloxan-induced diabetic rats.

Introduction: Diabetes mellitus causes hyperglycemia and associated complications to the brain. In current study, the traditionally reported remedial claims of Agave americana var. marginata has been scientifically investigated in diabetic rats. Methodology: The methanolic extract of leaves of Agave americana var. marginata (Aa.Cr) was characterized for total phenols, flavonoids, and antioxidant potential through in-vitro testing. The rats chronically pre-treated with Aa.Cr (400 and 600 mg/kg) for 45 days were challenged with alloxan-induced hyperglycemia. The dose-dependent effects of Aa.Cr on blood glucose levels and body weights were compared with diabetic rats using glibenclamide (0.6 mg/kg) as a standard. The animals were tested for diabetes-associated neurological comorbidities through behavioral and biochemical evaluation. Results: The phenols and flavonoids enriched Aa.Cr caused a significant dose-dependent hypoglycemic effect. Aa.Cr showed protection from comorbid anxiety, depression and cognitive impairment as compared to diabetic rats. The alanine aminotransferase, total cholesterol, triglycerides and low-density lipoprotein were prominently reduced, and high-density lipoprotein was increased in rats treated with Aa.Cr. Moreover, the oxidative stress in isolated brains was reduced by Aa.Cr. Conclusion: These findings suggest that Aa.Cr is enriched with antioxidant and anti-inflammatory phytoconstituents valuable for diabetes and related neurological complications.

Antidiabetic effects of Brugmansia aurea leaf extract by modulating the glucose levels, insulin resistance, and oxidative stress mechanism.

Background: Ethnopharmacological relevance: Brugmansia, a genus of the Solanaceae family, has historically been utilized in many different parts of the world as an anti-inflammatory for treating skin infections, wounds, and bodily aches and pains. The current study aimed to investigate the potential benefits of a methanolic extract of Brugmansia aurea in the management of diabetes and underlying complications in alloxanized-induced diabetic rats. Materials and methods: Animals were divided into nine groups (n = 6). Four groups received different standard oral hypoglycemic agents; three groups received 100, 200, and 400 mg/kg of B. aurea leaf extract for six consecutive weeks, and the remaining two were normal and disease control groups. All groups received alloxan (150 mg/kg) except for the normal control. Only those animals whose glucose levels were raised to 200 mg/dl were selected for the study. After a 6-week dosage period, various biochemical parameters, as well as HbA1c, antioxidant profile, oral glucose tolerance test (OGTT), insulin sensitivity, histopathology, and insulin resistance, were measured and compared with the untreated diabetic group. Results: Brugmansia aurea leaf extract at a dose of 400 mg/kg showed potent antidiabetic activity by reducing blood glucose levels (p < 0.001) after 6 weeks of treatment. OGTT data showed that B. aurea exhibited significant (p < 0.001) glucose tolerance by significantly reducing blood glucose levels in just 2 h post-treatment. Other tests showed that plant extract significantly increased (p < 0.001) insulin sensitivity and decreased (p < 0.001) insulin resistance. The biochemical profile showed reduced triglyceride and cholesterol, while the antioxidant profile showed restoration of antioxidant enzymes in the pancreas, kidney, and liver tissues of treated rats. Conclusion: The present study indicated that crude extracts of B. aurea increase insulin sensitivity and reduce hyperlipidemia in diabetic rats, which rationalizes the traditional medicinal use of this plant as an antidiabetic agent.