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Background: Type 1 diabetes is an autoimmune illness with high Th1 response that destroys the islets ß-cells causing their death. Insulin therapy for T1D cannot prevent the damaging immune response in pancreatic tissue. This study aimed to assess the effects of S. mansoni SEA antigen on experimentally induced-T1D as an immune therapy. Methods: five groups of mice (7 mice each) have been employed; Control - ve (I), STZ-treated (II); SEA-immunized (III), SEA-STZ prophylactic (IV) and SEA-STZ curative (V) groups. Biochemical data such as blood glucose, insulin level, and immunological markers such as insulin autoantibodies (IAA) and serum IL-10 level were used. Histological and immunohistochemical alterations in ß-cells have been investigated. Results: A potential immune effect of SEA in treating and preventing the development of T1D was recorded evident by lower blood glucose and higher blood insulin levels. Elevated serum IL-10 levels in both curative and preventive-SEA groups compared to the STZ-treated group, which had a typical pathological condition of T1D manifested as high blood glucose, low blood insulin, and a lower level of IL-10. The results of IAA levels, histological, and immunohistochemical tests in all groups were consistent with the biochemical data demonstrating an effective immunological modulatory impact of SEA on the course of T1D. Conclusions: This study contributes to the expanding body of data supporting the efficacy of S. mansoni antigens on autoimmune diabetes. More studies are needed to determine the complete immunological effect of parasitic helminths, in order to create innovative pharmacological therapies for human use. [ABSTRACT FROM AUTHOR]

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AbstractObjectiveMaterial and MethodsResultsConclusionThis study aimed to demonstrate the protective effect of beta-carotene against STZ-induced DN in rats and explore the possible underlying mechanisms that may have mediated such condition.Wistar rats were allocated into four groups. Normal group received distilled water for 3 weeks. The other three groups were rendered diabetic by an intraperitoneal dose of STZ (50 mg/kg), 48 h later, group 2: received the vehicle and served as control, groups (3 &4) received orally beta-carotene in doses of 10 and 20 mg/kg, respectively for 3 weeks. Then serum and renal tissue were collected for biochemical, molecular, immunohistopathological, and histopathological examination.Beta-carotene ameliorated the reduction in body weight, reduced blood glucose, elevated serum insulin, reduced blood urea nitrogen, and serum creatinine levels. Beta-carotene elevated phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK)/AMPK, alleviated phosphorylated mammalian target of rapamycin (p-mTOR)/mTOR, reduced interleukin 1 beta (IL-1β), increased Beclin 1, LC3II/LC3I, and reduced p62 renal contents. Moreover, it elevated renal SIRT1 gene expression and reduced renal tumor necrosis factor-alpha (TNF-α) and caspase-3 protein expressions.Beta-carotene exerted renoprotective effect against STZ-induced DN and histopathological alterations through alleviating hyperglycemia, attenuating inflammation, activating AMPK/SIRT1/autophagy pathway, and combating apoptosis. [ABSTRACT FROM AUTHOR]

Rosa davurica Pall. is widely used in traditional oriental herbal therapy, but its components and molecular mechanisms of action remain unclear. This study investigates the antidiabetic potential of Rosa davurica Pall. root extract (RDR) and elucidates its underlying molecular mechanisms with in vitro and in vivo models. Data from the current study show that RDR exhibits strong antioxidant activity and glucose homeostasis regulatory effects. It significantly impacts glucose homeostasis in C2C12 skeletal muscle cells by inhibiting α-glucosidase activity. Further molecular mechanistic studies revealed that RDR promoted glucose uptake by phosphorylation of AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC), but not Phosphatidylinositol 3-kinase (PI 3-kinase)/Akt in C2C12 skeletal muscle cells. These actions increased the expression and translocation of glucose transporter type 4 (GLUT4) to the plasma membrane. In addition, RDR treatment in the STZ-induced diabetic rats remarkably improved the low body weight, polydipsia, polyphagia, hyperglycemia, and islet architecture and increased the insulin/glucose ratio. The liver (ALT and AST) and kidney marker enzyme (BUN and creatinine) levels were restored by RDR treatment as well. Phytochemical analysis identified eight major constituents in RDR, crucial for its antioxidant and antidiabetic activity. Through the molecular docking of representative glucose transporter GLUT4 with these compounds, it was confirmed that the components of RDR had a significantly high binding score in terms of structural binding. These findings from the current study highlight the antidiabetic effects of RDR. Collectively, our data suggest that RDR might be a potential pharmaceutical natural product for diabetic patients. [ABSTRACT FROM AUTHOR]

The prevalence of testicular dysfunction is increasing as it is a common diabetes mellites (DM) complication. The objective of this study is to explore the potential protective effect of sulbutiamine against testicular hypofunction associated with streptozotocin (STZ)‐induced DM in rats. Sulbutiamine was administered orally (60 mg/kg) to male Wistar rats for 8 weeks starting 72 h after a single injection of STZ (45 mg/kg, i.p.). Blood glucose level (BGL), serum testosterone level, sperm number, and motility were determined. Testicular tissue was examined histopathologically, and the Johnson score was evaluated. Levels of malondialdehyde (MDA), protein kinase C (PKC), nuclear factor erythroid‐derived 2‐like 2 (Nrf2), and proliferating cell nuclear antigen (PCNA) were measured. Apoptosis was evaluated by immunohistochemical determination of B‐cell lymphoma protein 2 (Bcl‐2), Bcl‐2 associated X‐protein (Bax), and caspase‐3. Sulbutiamine administration managed to reduce BGL and boost testicular function as manifested by increased testicular weight, testosterone level, sperm number, and motility compared to the STZ group. Additionally, histopathological examination revealed an improved histological picture and Johnson score of testicular tissue after sulbutiamine treatment. Sulbutiamine administration reduced testicular PKC, MDA, and PCNA levels and increased Nrf2 compared to the untreated group. Moreover, sulbutiamine treatment suppressed apoptosis triggered by STZ as evidenced by elevated Bcl‐2, decreased Bax and reduced caspase‐3. The present work revealed for the first time a promising protective role of sulbutiamine against STZ‐induced testicular dysfunction which may add to the clinical utility of sulbutiamine. The underlying mechanisms involve reducing BGL and PKC, activating Nrf2 and inhibiting apoptosis. [ABSTRACT FROM AUTHOR]

Cytokine-induced β-cell apoptosis is a major pathogenic mechanism in type 1 diabetes (T1D). Despite significant advances in understanding its underlying mechanisms, few drugs have been translated to protect β-cells in T1D. Epigenetic modulators such as bromodomain-containing BET (bromo- and extra-terminal) proteins are important regulators of immune responses. Pre-clinical studies have demonstrated a protective effect of BET inhibitors in an NOD (non-obese diabetes) mouse model of T1D. However, the effect of BET protein inhibition on β-cell function in response to cytokines is unknown. Here, we demonstrate that I-BET, a BET protein inhibitor, protected β-cells from cytokine-induced dysfunction and death. In vivo administration of I-BET to mice exposed to low-dose STZ (streptozotocin), a model of T1D, significantly reduced β-cell apoptosis, suggesting a cytoprotective function. Mechanistically, I-BET treatment inhibited cytokine-induced NF-kB signaling and enhanced FOXO1-mediated anti-oxidant response in β-cells. RNA-Seq analysis revealed that I-BET treatment also suppressed pathways involved in apoptosis while maintaining the expression of genes critical for β-cell function, such as Pdx1 and Ins1. Taken together, this study demonstrates that I-BET is effective in protecting β-cells from cytokine-induced dysfunction and apoptosis, and targeting BET proteins could have potential therapeutic value in preserving β-cell functional mass in T1D. [ABSTRACT FROM AUTHOR]

Worldwide spread in the incidence of diabetes justified the need of extensive research in an appropriate model system to develop an effective treatment strategy for diabetology. In recent years, because of animal ethical issues and limitations, the silkworm (Bombyx mori) has emerged as a perfect invertebrate model for various biomedical experiments. However, there are several issues related to induce hyperglycaemia in the mammalian system that have not been studied in the silkworms. In the present study, we investigated the consequences of induced hyperglycaemia by oral and intravascular administration of streptozotocin (STZ) and glucose in the silkworms. Interestingly, results confirmed the competence of STZ to induce hyperglycaemia when administered through intravascular route, but suppress the glucose concentration if administrated orally in the silkworms. Comparatively, the severity of induced hyperglycaemia in the silkworms remained nearly the same in response to the oral and intravascular administration of glucose. Furthermore, prolonged administration of STZ has recorded negative effect on the growth rate of the silkworms, whereas a drastic decline in the same was reported in the silkworms administered with glucose. Notably, these results confirm that the response shown by the silkworms to STZ is very similar to that of mammals, making it an excellent model to study diabetic complications and consequences associated with STZ in diabetology. [ABSTRACT FROM AUTHOR]

Diabetic people have a much higher rate of cardiovascular disease than healthy people. Therefore, heart and aortic tissues are target tissues in diabetic research. In recent years, the synthesis of new vanadium complexes and investigation of their antidiabetic/lowering effect on the blood glucose levels and antioxidant properties are increasing day by day. Our study aimed to examine the effects of synthesized oxovanadium (IV) complex of 2-[(2,4-dihydroxybenzylidene]hydrazine-1-[(N-(2-hydroxybenzylidene)](S-methyl)carbothioamide [VOL] on diabetic heart and aortic tissues, as well as in vitro lactate dehydrogenase (LDH) and myeloperoxidase (MPO) inhibition, antioxidant properties, and reducing power. Electrochemical characterization of the VOL was carried out by using Cyclic Voltammetry (CV) and Linear Sweep Voltammetry (LSV) methods. In addition, in silico drug-likeness and ADME prediction were also investigated. For in vivo study, male Swiss albino rats were randomly selected and separated into four groups which are control, control + VOL, diabetic and diabetic + VOL. After the experimental procedure, biochemical parameters were investigated in homogenates of heart and aorta tissues. The results showed that VOL has a protective effect on heart and aortic tissue against oxidative stress. According to electrochemical experiments, one reversible oxidative couple and one irreversible reductive response were observed for the complex. In addition, in vitro LDH and MPO inhibition of VOL was examined. It was found that VOL had a protective effect on heart and aortic tissues of diabetic rats, and caused the inhibition of LDH and MPO in in vitro studies. On the other hand, evaluating the synthesized VOL according to in silico drug-likeness and absorption, distribution, metabolism, and excretion (ADME) prediction, it was found that VOL has drug-like properties and exhibited high gastrointestinal absorption. The VOL had a therapeutic impact on the heart and aortic tissues of diabetic rats, according to the findings. [ABSTRACT FROM AUTHOR]

Abstract Background The sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA2a) depression substantially contributes to diastolic dysfunction in heart failure (HF), suggesting that SERCA2a stimulation may be a mechanism-based HF therapy. Istaroxime is a drug endowed with both a SERCA2a stimulatory activity and a Na+/K+ pump inhibitory activity for acute HF treatment. Its main metabolite PST3093 shows a more favorable therapeutic profile as compared to the parent drug, but it is still unsuitable for chronic usage. Novel PST3093 derivatives have been recently developed for oral (chronic) HF treatment; compound 8 was selected among them and here characterized. Methods Effects of compound 8 were evaluated in a context of SERCA2a depression, by using streptozotocin-treated rats, a well-known model of diastolic dysfunction. The impact of SERCA2a stimulation by compound 8 was assessed at the cellular level ad in vivo, following i.v. infusion (acute effects) or oral administration (chronic effects). Results As expected from SERCA2a stimulation, compound 8 induced SR Ca2+ compartmentalization in STZ myocytes. In-vivo echocardiographic analysis during i.v. infusion and after repeated oral administration of compound 8, detected a significant improvement of diastolic function. Moreover, compound 8 did not affect electrical activity of healthy guinea-pig myocytes, in line with the absence of off-target effects. Finally, compound 8 was well tolerated in mice with no evidence of acute toxicity. Conclusions The pharmacological evaluation of compound 8 indicates that it may be a safe and selective drug for a mechanism-based treatment of chronic HF by restoring SERCA2a activity. Graphical Abstract

Diabetic nephropathy (DN) is reported as one of the most serious microvascular diabetic complications and the trigger of end-stage renal disease (ESRD), underscoring the concern of any therapeutic intervention directed at ameliorating the development and progression of DN. The current study explored the renoprotective impact of montelukast (Mon) against streptozotocin (STZ)-induced DN in rats compared to a standard anti-hyperglycemic insulin (Ins) treatment. Diabetes was induced by a single dose of STZ (55 mg/kg). Diabetic rats were treated with Mon (10 and 20 mg/kg, oral gavage) for eight weeks. Mon administration for 8 weeks after induction of diabetes conferred significant dose-dependent renoprotection, independent of blood glucose levels (unlike Ins), as evidenced by the improvement in serum creatinine, and blood urea nitrogen (BUN), and ameliorated STZ-induced renal necrotic, inflammatory alterations, and renal fibrosis. Additionally, Mon treatment in diabetic rats significantly restored redox hemostasis as evidenced by malondialdehyde (MDA) and total antioxidant capacity (TAC) levels; significantly reduced the renal expression of high mobility group box (HMGB) 1, toll-like receptor (TLR) 4, nuclear factor kappa B (NF-κB) (in the nucleus), NOD-like receptor family pyrin domain containing (NLRP) 3, and interleukin (IL)-1β. Moreover, Mon administration ameliorated the dysregulation in autophagy as evidenced by p62 and microtubule-associated protein 1A/1B-light chain 3 (LC3)-II levels. In conclusion, the renoprotective effect of Mon is potentially associated with its modulatory effect on inflammatory cytokines, antioxidant properties, and autophagy. Renoprotective effect of montelukast and its underlying pathway: Hyperglycemia and advanced glycation end products (AGEs) stimulate the release of high mobility group box (HMGB) 1 from necrotic and inflammatory cells. HMGB1 is considered as one of the endogenous ligands of toll-like receptor (TLR) 4, and the interaction of HMGB1 with TLR4 results in a subsequent translocation of nuclear factor kappa B (NF-κB) from the cytoplasm into the nucleus inducing an inflammatory response. NF-κB is a key mediator of the priming signal responsible for the activation of NOD-like receptor family pyrin domain containing (NLRP) 3 inflammasome by stimulating the expression of both NLRP3 and pro- interleukin (IL)-1β, which is then converted to IL-1β by to mediate inflammation. NLRP3 can induce reactive oxygen species production, while autophagy inhibits AGEs and NLRP3 accumulation. Montelukast show an inhibitory effect on HMGB1, TLR4, NF-κB, NLRP3, and IL-1β and has autophagy stimulating characteristics indicating its potential renoprotective effect. [ABSTRACT FROM AUTHOR]

Introduction: The objective of the study was to determine antidiabetic and antihyperlipidemic effects of Mangifera camptosperma leaves extract using streptozotocin-induced animal model. Methods: The leaves of M. camptosperma extracted with hydroethanolic (50:50) solvent using soxhlet apparatus. Traditional Chinese medicine (TCM) is often given as an adjuvant to alleviate diabetic symptoms. The plant extracts were used to determine presence of phytochemicals present in them using different tests. Diabetes was induced on animals using streptozotocin (STZ) 50 mg/kg through intra-peritoneal route. Oral administration of M. camptosperma extract at doses of 200 mg/kg and 400 mg/kg was used to assess its antidiabetic and antihyperlipidemic effects. Results: The phytochemical analysis showing presence of carbohydrates, alkaloids, tannins, glycosides, and flavonoids. The diabetic control group had blood glucose levels of 102 mg/kg and 126 mg/kg, respectively, after receiving the test medication, but the diabetic rats treated with the extract showed a substantial decrease to 90.11 ± 5.71 (200 mg/kg) and 82.12 ± 3.99 (400 mg/kg). If compared to the diabetic control group, the administration of 400 mg/kg of M. camptosperma for 21 days resulted in a substantial decrease (p < 0.05) in serum total cholesterol (106.12 ± 5.94 mg/dL) and triglyceride (83.11 ± 4.04 mg/dL), as well as an increase in HDL cholesterol (36.15 ± 3.04 mg/dL). This study found that while administered to diabetic rats, M. camptosperma lowered blood glucose levels and improved lipid profiles. Discussion: It can be concluded from the study that the plant extract may be useful in treating hyperlipidemic and type-2 diabetes as an alternative medicine.

Zebrafish is a developing vertebrate model with several advantages, including its small size, and high experimental efficiency. Malaysia exhibit one of the highest diabetes rates in the Western Pacific and incurring an annual cost of 600 million US dollars. The objective of the study is to determine the antidiabetic properties of green honey (GH) using a zebrafish model. Adult zebrafish, aged 3–4 months, were subjected to overfeeding and treated with streptozotocin (STZ) through intraperitoneal injection (IP) on days 7 and 9. The study assessed the oral sucrose tolerance test (OSTT) and the anti-diabetic effects of green honey. The evaluation was conducted at three time points: 30, 60, and 120 min after treatment and sucrose administration. The study utilised a model with a sample size of 5. The study was performed in six groups. These groups are (1) Normal control (non-diabetic, no intervention), (2) Normal control + GH (non-diabetic, supplemented with GH 3 μl), (3) DM control (diabetic, no intervention), (4) DM Gp1 (diabetic, 3 μL GH), (5) DM Gp2 (diabetic, 6 μ L GH), (6) DM Acarbose (diabetic, treated with acarbose). Fasting blood glucose levels for non-diabetic (non-DM) and diabetic (DM) groups were evaluated before and after the 10 days of diabetic induction. DM groups (excess of food and two injections of STZ) have caused a significant increment in the fasting blood glucose to 11.55 mmol/l (p

Diabetes is a ubiquitous disease that causes several complications. It is associated with insulin resistance, which affects the metabolism of proteins, carbohydrates, and fats and triggers liver diseases such as fatty liver disease, steatohepatitis, fibrosis, and cirrhosis. Despite the effectiveness of Sitagliptin (ST) as an antidiabetic drug, its role in diabetes-induced liver injury is yet to be fully investigated. Therefore, this study aims to investigate the effect of ST on hepatic oxidative injury, inflammation, apoptosis, and the mTOR/NF-κB/NLRP3 signaling pathway in streptozotocin (STZ)-induced liver injury. Rats were allocated into four groups: two nondiabetic groups, control rats and ST rats (100 mg/kg), and two diabetic groups induced by STZ, and they received either normal saline or ST for 90 days. Diabetic rats showed significant hyperglycemia, hyperlipidemia, and elevation in liver enzymes. After STZ induction, the results revealed remarkable increases in hepatic oxidative stress, inflammation, and hepatocyte degeneration. In addition, STZ upregulated the immunoreactivity of NF-κB/p65, NLRP3, and mTOR but downregulated IKB-α in liver tissue. The use of ST mitigated metabolic and hepatic changes induced by STZ; it also reduced oxidative stress, inflammation, and hepatocyte degeneration. The normal expression of NF-κB/p65, NLRP3, mTOR, and IKB-α were restored with ST treatment. Based on that, our study revealed for the first time the hepatoprotective effect of ST that is mediated by controlling inflammation, oxidative stress, and mTOR/NF-κB/NLRP3 signaling. [ABSTRACT FROM AUTHOR]

Objectives: Presently, diabetes is a major chronic metabolic abnormality characterized by sustained hyperglycemia. Diabetic neuropathy, encephalopathy, diabetes induced anxiety, depression is common life-threatening complications in which hyperglycemia mediated oxidative stress plays major role in pathogenesis. Sinapic acid is a phenolic acid, reported with anti-inflammatory, antioxidant, anti-bacterial, anti-tumor, anxiolytic activity and also it is proven to be neuroprotective in diabetic neuropathy. Materials and Methods: This study was designed to evaluate anti-depressant activity of Sinapic acid on STZ induced diabetic Wistar rats. Animals were divided into six groups (n=6). Diabetes was induced by single dose of STZ injection 55 mg/kg i.p. and sinapic acid was administered orally (5, 10, 20 mg/kg) after confirmation of hyperglycemia for next 4 weeks. Behavioural parameters like tail suspension test and forced swim test, antioxidant enzymes (SOD, GSH), oxidative stress (NO, MDA), total protein level were estimated and morphology of brain was examined histopathologically. Results: The results suggested that sinapic acid have decreased duration and percent of immobility, oxidative stress and increased antioxidant enzymes and total protein level. Morphological damage and neuronal degeneration in brain tissue was normalised by Sinapic acid. Conclusion: Thus, Sinapic acid shows antidepressant activity in diabetes induced depression. [ABSTRACT FROM AUTHOR]

One of the most widespread metabolic diseases, Type-2 Diabetes Mellitus (T2DM) is defined by high blood sugar levels brought on by decreased insulin secretion, reduced insulin action, or both. Due to its cost-effectiveness and eco-friendliness, plant-mediated green synthesis of nanomaterials has become more and more popular. The aim of the study is to synthesize AgNPs, their characterizations and further in-vitro and in-vivo studies. Several methods were used to morphologically characterise the AgNPs. The AgNPs were crystalline, spherical, and clustered, with sizes ranging from 20 to 50 nm. AgNPs were found to contain various functional groups using Fourier transform infrared spectroscopy. This study focuses on the green-synthesis of AgNPs from Fagonia cretica (F. cretica) leaves extract to evaluate their synthesized AgNPs for in-vitro and in-vivo anti-diabetic function. For the in-vivo tests, 20 male Balb/C albino-mice were split up into four different groups. Anti-diabetic in-vivo studies showed significant weight gain and a decrease in all biochemical markers (pancreas panel, liver function panel, renal function panel, and lipid profile) in Streptozotocin (STZ)-induced diabetic mice. In vitro anti-diabetic investigations were also conducted on AgNPs, comprising α-amylase, α-glucosidase inhibitions, and antioxidant assays. AgNPs showed antioxidant activity in both the DPPH and ABTS assays. The research showed that the isolated nanoparticles have powerful antioxidant and enzyme inhibitory properties, especially against the main enzymes involved in T2DM.

There is an excellent approach to design antidiabetic drugs based on inhibitors of α-glucosidase. These inhibitors control the sugar level in blood of diabetic patients to avoid complications on patient health. In current study we designed a new series of oxadiazole based derivatives (1–20). All synthesized analogues were characterized through 1H-NMR, 13C-NMR, HREI-MS and evaluated against α-glucosidase inhibitory potential and analogues 1, 4, 16, 17, and 19 showed excellent activity ranging 1.10–8.60 μM. The analogues 2, 3, 5, 6, 10, 14, and 18 showed 4 to 2 folds better activities ranging 10.10–21.30 μM than standard drug standard acarbose (IC50 = 38.40 ± 0.80 μM). The analogues 11, 13, and 20 showed activities ranging 34.30–34.60 μM better than standard. The analogues 7, 12, and 15 showed weak activities. The analogues 8 and 9 found completely inactive. The binding interactions of these active derivatives were confirmed through molecular docking. The docked analogues, and the α-glucosidase exhibited negative bending energies. The inhibition of α-glucosidase via tested analogues were thermodynamically favored. Based on these results, analog 1 was evaluated against STZ induced diabetic rats and found potent at a dose of 200 mg/kg. [ABSTRACT FROM AUTHOR]

Background: Because neuropathic pain is currently a poorly understood medical condition, there is a need to identify a more effective therapeutic drug with a low toxicity profile. Purpose: To address the behavioural, oxidative stress, and cytokine-mediated inflammatory pathways involved in sciatic nerve, the current study protocol used Chronic Constriction Injury (CCI) and Streptozotocin (STZ) induced neuropathic pain methods. Materials and Methods: Following CCI to the sciatic nerve and administration of STZ 60mg/kg, rats develop painful neuropathy characterized by hyperalgesia, allodynia, oxidative stress, neuroinflammation, and increased total calcium levels. Results: Topiramate (20, 40, and 80 mg/kg) treatment for two weeks beginning on the 15th day of CCI surgery and ending on the 29th day of diabetes confirmation significantly and dose dependently reduced the development of allodynia and hyperalgesia. Furthermore, topiramate treatment produced significant dose-dependent antioxidant and anti-inflammatory effects by restoring the balance of oxidative stress and decreasing the levels of inflammatory markers such as TNF-a, IL-1, and IL-6, as well as total calcium in sciatic nerve homogenate. Conclusion: To summarize, the treatment with different doses of topiramate produces analgesic, antioxidant, and anti-inflammatory effects in a dose dependent manner, owing to the increased curiosity to understand the underlying pain producing mechanism and its translation into signs and symptoms of CCI and STZ induced neuropathy. [ABSTRACT FROM AUTHOR]

Abstract Background Diabetes mellitus (DM) is a growing disease across the world; diabetes is a complex metabolic disorder in which blood glucose concentration level increases and continue for a prolonged period due to a decrease secretion of insulin or action, resulting in the disorder of carbohydrate, lipid, and protein metabolism. The plant-related bioactive compounds have proven their efficacy with least toxicities and can be utilized for the disease treatment. Our objective is to elucidate the mechanism of action of plant bioactive compounds which can give future direction in diabetes treatment. Main body In this review paper, we briefly study more than 200 research papers related to disease and bioactive compounds that have therapeutic applicability in treatment. The plant contains many bio-active compounds which possess in vitro and in vivo anti-diabetic effect which may be responsible for the hypoglycaemic property by inhibiting the digestive enzyme i.e. alpha-amylase and alpha-glucosidase, by producing mimetic action of insulin, by reducing the oxidative stress, by showing antihyperglycemic activity and hypolipidemic activity, by inhibition of aldose reductase, and by increasing or enhancing glucose uptake and insulin secretion. Conclusion Our study revealed that terpenes, tannin, flavonoids, saponin, and alkaloids are important bioactive constituents for anti-diabetic activity. The mechanistic approach on alpha-glucosidase and alpha-amylase, hypolipidemic activity, and AR inhibitory action clear-cut explain the therapeutic applicability of these bioactive compounds in disease. Plants that contain these bioactive compounds can be good drug candidates for future research on diabetes treatment.

AbstractContext The reduction in M2 macrophage polarisation plays a major role during diabetic wound healing. Resveratrol (RSV) can promote the polarisation of M2 macrophages and accelerate diabetic wound healing. However, the specific mechanism by which RSV regulates M2 macrophage polarisation to promote diabetic wound healing is unclear.Objective This study evaluated the effectiveness of RSV on diabetic wound healing and analysed the underlying mechanisms.Materials and methods STZ-induced C57/B6 mice were used as a diabetic mice model for a period of 15 days. RSV (10 μmol/L) was injected around the wound to evaluate the effect of RSV on the healing process of diabetic wounds. The human monocyte line THP-1 was used to evaluate the effects of RSV (10 μmol/L) on polarisation of M2 macrophages and the secretion of pro-inflammatory factors.Results In vivo, RSV significantly increased diabetic wound healing (p

Diabetes is a metabolic disorder characterized by hyperglycemia resulting from either the deficiency in insulin secretion or the action of insulin Diabetes can affect numerous different organ systems in the body and, over time, can lead to serious complications. Complications are microvascular or macrovascular. To evaluate the anti-diabetic effect of Phyllanthus niruri silver nano-particles. Streptozotocin (STZ) of 50mg/kg is used to induce diabetes in wistar rats. The wistar rats were distributed to six different groups. Group-I represented as Control; Group-II represented as diabetic control (STZ ); Group-III represented as 5 mg/kg body weight of glibenclamide + diabetes; Group-IV represented as phyllanthus niruri extract + diabetes; Group-V represented as 100 µg Phyllanthus niruri silver nanoparticles + diabetes; group-6- Phyllanthus niruri silver nanoparticles150µg + diabetes. The silver nanoparticles were inspected for the morphological and optical properties investigated using UV spectrophotometer, SEM and FT-IR techniques. The AgNPs has shown characteristic peak at 428nm.The study revealed that the AgNPs treatment reduced serum blood glucose concentrations remarkable improvement in the body weight, Abnormal high serum levels in diabetes treatment with AgNp's they reached to normal in STZ-challenged diabetic rats. The histopathological alterations were also studied in all the experimental animals. The pathology results revealed that the AgNPs treatment induces the regeneration of islets cells of pancreas in the experimental rats. The research study proved that the Phyllanthus niruri AgNPs exerts anti-diabetic properties. [ABSTRACT FROM AUTHOR]

Rosmarinic acid (RA), a natural ester phenolic compound, is known to have antioxidant and anti-inflammatory properties. RA has also been reported to exhibit a hypoglycemic effect; however, the mechanisms underlying this effect have yet to be investigated. Therefore, the present study focused on the anti-diabetic effects and mechanism of RA in INS-1 cells using in vitro model. Streptozotocin (STZ) at a concentration of 3 mM was applied to INS-1 cells for 4 h to create a diabetic model. The cells were pretreated for 24 h with various concentrations (1 and 2.5 μM) of RA. The Cell viability, glucose-stimulated insulin secretion (GSIS), glucose uptake, lipid peroxidation, reactive oxygen species (ROS), apoptosis, and protein expression of Bcl-2, NF-κB, 1L-1β, and PARP were assessed. Results showed that STZ-treated INS-1 cells exhibited reduced cell viability, insulin release, insulin content, glucose uptake, and elevated MDA and ROS levels. Cells pretreated with RA maintained the function and morphology of β-cells against STZ-induced damage. Moreover, RA sustained high protein expression levels of Bcl-2 and low expression levels of NF-κB, IL-1β, and PARP. In conclusion, RA preserved β-cells function against STZ-induced damage by altering NF-κB and Bcl-2 pathways.

BackgroundDiabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes.ObjectiveThis study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how β-cells of the pancreas in diabetic rats respond to MT administration.Materials and methodsForty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively.ResultsMT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the β-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic β-cells; its antioxidant effect also reduced hepatocyte injury.ConclusionCollectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic β-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes.

Introduction: Alzheimer’s disease (AD) patients suffer from anxiety and depression. Pioglitazone (PIOG) is effective in the treatment of neurodegenerative diseases. The present study aimed to investigate the therapeutic efficacy of PIOG on anxiety and depression symptoms in the Streptozotocin (STZ) rat model of AD. Methods: All the animals were divided into six groups: Control, DMSO, PIOG, sham-operated, STZ, and STZ plus DMSO or PIOG. For induction of AD, STZ (3mg/kg, 5μl/injection site) was injected into the lateral ventricles. After injection of PIOG(10 μl) or DMSO for 21 days, the behavioral tests were performed using sucrose preference, light-dark box, and elevated plus maze test. Results: The results showed that the STZ injection significantly reduced the entries, duration of presence in the light compartment and open arm of the elevated plus maze, and a percentage of sucrose preference compared to the control group. PIOG treatment in STZ-treated rats significantly increased the entries, duration of presence in the light compartment and open arm of the elevated plus maze, and a percentage of sucrose preference that indicated anti-depression and anxiolytic-like effects. Conclusion: Based on our findings, the PIOG injection can reduce anxiety and depression-related behaviors in Alzheimer's rats. [ABSTRACT FROM AUTHOR]

Aegle Marmelos is a traditional medicinal plant in India which belongs to Rutaceae family which possesses innumerable health benefits. The entire plant body including its leaves, stem, root, inflorescence and seed are proved to be significant medicinal value and hence it is one among the inevitable plant used in the preparation of various Ayurvedic pharmacological products. The plant is a rich source of various components including eugenol, Vicenin-2, linoleic acid, oleic acid, rosmarinic Calcium, Phosphorous and many more. Its Ethnopharmacological properties such as Anti-diabetic, Anticancerous, Analgesic, Anti-inflammatory, Radio-protective. In vivo toxicity study concluded that no mortality was find in toxicity study. [ABSTRACT FROM AUTHOR]

A hydrophobic Cu 2 O cathode (Cu x O-L) was designed to solve the challenge of low oxidation ability in electro-Fenton (EF) for treating emerging pollutants. This fabrication process involved forming Cu(OH) 2 nanorods by oxidizing copper foam (Cu-F) with (NH 4) 2 S 2 O 8 , followed by coating them with glucose via hydrothermal treatment. Finally, a self-assembled monolayer of 1-octadecanethiol was introduced to create a low-surface-energy, functionalized Cu x O-L cathode. Results exhibited an approximately 7.9-fold increase in hydroxyl radical (·OH) generation compared to the initial Cu-F. This enhancement was attributed to two key factors: (Ⅰ) the superior O 2 -capturing ability of Cu x O-L cathode, which led to high H 2 O 2 production due to a 2 nm thick hydrophobic gas layer facilitated O 2 -capturing; (Ⅱ) a relative high concentration of Cu+ at the Cu x O-L cathode promoted the activation of H 2 O 2 into·OH. In addition, the performance of EF with the Cu x O-L cathode using sulfathiazole (STZ) as a model pollutant was evaluated. This study offers valuable insights into the design of O 2 -capturing cathodes in EF processes, particularly for treating emerging organic pollutants. [Display omitted] • Bio-inspired hydrophobic Cu 2 O cathode (Cu x O-L) was designed； • ·OH concentration on Cu x O-L cathode increased approximately 7.9-fold; • A 2-3 nm gas film enhances the cathode's O 2 capturing; • Cu+ was active site for H 2 O 2 formation, favoring its activation into·OH. [ABSTRACT FROM AUTHOR]

Diabetes is a ubiquitous disease that causes several complications. It is associated with insulin resistance, which affects the metabolism of proteins, carbohydrates, and fats and triggers liver diseases such as fatty liver disease, steatohepatitis, fibrosis, and cirrhosis. Despite the effectiveness of Sitagliptin (ST) as an antidiabetic drug, its role in diabetes-induced liver injury is yet to be fully investigated. Therefore, this study aims to investigate the effect of ST on hepatic oxidative injury, inflammation, apoptosis, and the mTOR/NF-κB/NLRP3 signaling pathway in streptozotocin (STZ)-induced liver injury. Rats were allocated into four groups: two nondiabetic groups, control rats and ST rats (100 mg/kg), and two diabetic groups induced by STZ, and they received either normal saline or ST for 90 days. Diabetic rats showed significant hyperglycemia, hyperlipidemia, and elevation in liver enzymes. After STZ induction, the results revealed remarkable increases in hepatic oxidative stress, inflammation, and hepatocyte degeneration. In addition, STZ upregulated the immunoreactivity of NF-κB/p65, NLRP3, and mTOR but downregulated IKB-α in liver tissue. The use of ST mitigated metabolic and hepatic changes induced by STZ; it also reduced oxidative stress, inflammation, and hepatocyte degeneration. The normal expression of NF-κB/p65, NLRP3, mTOR, and IKB-α were restored with ST treatment. Based on that, our study revealed for the first time the hepatoprotective effect of ST that is mediated by controlling inflammation, oxidative stress, and mTOR/NF-κB/NLRP3 signaling.

Diabetes mellitus (DM) is a chronic progressive metabolic disorder associated with several gastrointestinal complications, affecting up to 75% of patients. Knowing that Angiotensin II (AngII) also regulates intestinal contraction, we decided to evaluate changes in ileum and colon histomorphometry and AngII reactivity in a rat model of DM. Streptozotocin (STZ, 55 mg/kg) was administered to induce DM to 24 adult male Wistar rats. Diabetic rats displayed all the characteristic signs of type 1 DM (T1DM) and fecal excretion increased about 4-fold over 14 days, while the excretion of controls remained unaltered. Compared to controls, diabetic ileum and colon presented an increase in both macroscopic (length, perimeter and weight) and microscopic (muscular wall thickness) parameters. Functionally, AngII-induced smooth muscle contraction was lower in diabetic rats, except in the distal colon. These differences in the contractile response to AngII may result from an imbalance between AngII type 1 (antagonized by candesartan, 10 nM) and type 2 receptors activation (antagonized by PD123319, 100 nM). Taken together, these results indicate that an early and refined STZ-induced T1DM rat model already shows structural remodelling of the gut wall and decreased contractile response to AngII, findings that may help to explain diabetic dysmotility. [ABSTRACT FROM AUTHOR]

This study was designed to investigate the chemical profile, antihyperglycemic and antilipidemic effect of total methanolic extract (TME) of Bassia eriophora and isolated pure compound umbelliferone (UFN) in high-fat diet (HFD)- and streptozotocin (STZ)- induced diabetic rats. TME was subjected to various techniques of chromatography to yield UFN. Diabetes was induced after eight weeks of HFD by administration of STZ (40 mg/kg) intraperitoneally, and experimental subjects were divided into five groups. The diabetic control showed an increase in levels of blood glucose throughout the experiment. Treatments were initiated in the other four groups with glibenclamide (GLB) (6 mg/kg), TME (200 mg/kg and 400 mg/kg) and isolated UFN (50 mg/kg) orally. The effect on blood glucose, lipid profile and histology of the pancreatic and adipose tissues was assessed. Both 200 and 400 mg/kg of TME produced a comparably significant decrease in blood glucose levels and an increase in insulin levels with GLB. UFN began to show a better blood sugar-lowering effect after 14 days of treatment, comparatively. However, both 400 mg/kg TME and UFN significantly returned blood glucose levels in diabetic rats compared to normal rats. Analysis of the lipid profile showed that while HFD + STZ increased all lipid profile parameters, TME administration produced a significant decrease in their levels. Histopathological examinations showed that treatment with TME and UFN revealed an improved cellular architecture, with the healthy islets of Langerhans and compact glandular cells for pancreatic cells distinct from damaged cells in non-treated groups. Conversely, the adipose tissue displayed apparently normal polygonal fat cells. Therefore, these results suggest that TME has the potential to ameliorate hyperglycemia conditions and control lipid profiles in HFD + STZ-induced diabetic rats. [ABSTRACT FROM AUTHOR]

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Background: An ideal anti-diabetic type-1 pharmacotherapy should combine abrogation of beta cell pyroptosis with enhancement of beta cell mass., Objectives: The study investigated the potential synergism from combining the Bacillus Calmette-Guerin (BCG) vaccine with liraglutide (LIR) and probiotics in mitigating Streptozocin (STZ)-induced Type1diabetes mellitus in albino rats via suppression of TXNIP/NLRP3 signaling. Methods: Induction of diabetes was performed by two I.V. injections of 50 mg/kg of STZ in male Wistar rats. Forty-eight rats were randomly allocated into six groups: Normal control group; STZ -diabetic group; BCG group; BCG + LIR group; BCG + probiotic group; BCG + LIR + probiotic group. The rats were sacrificed after 8 weeks of treatment., Results: The STZ-diabetic group exhibited significant elevation of fasting blood sugar and HbA1c with remarkably decreased serum insulin along with a considerable increase in pancreatic proinflammatory cytokines (TNF-α, NLRP3, IL-1β, and NFκB) and apoptotic markers (ASK-1, IAPP, TXNIP, and Caspase-3) with prominently compromised oxidative scavenging capacity in addition to structural alteration in the pancreatic histoarchitecture with decreased insulin immunostaining. Conversely, diabetic-treated groups, especially the BCG + LIR + probiotic group, were superior in amelioration of STZ-induced pyroptosis of pancreatic islets evidenced by a significant decline in inflammatory cytokines and apoptotic markers with a remarkable upgrade in redox balance, Furthermore, the mitigation in the altered histopathological picture of the pancreas with enhanced insulin immunostaining has been was mirrored on the significant improvement of glucose homeostasis parameters., Conclusions: Noteworthy, BCG combination with liraglutide and probiotic might be a promising repurposed therapeutic modality in the management of type-1 diabetes mellites via targeting pancreatic TXNIP/NLRP3 signaling pathway., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Autophagy has been demonstrated to have a beneficial effect on diabetic nephropathy (DN). Rapamycin, an inhibitor of mTOR, was shown to stimulate β-cell autophagy. However, its effects on preventing or ameliorating DN is unclear, and its effects are worth studying. As fasting is now an attractive protective strategy, we aim to compare its effect to rapamycin effects on pancreatic and renal cells. Twenty-eight adult male Wistar Albino rats were randomly divided into four groups, using streptozotocin (STZ) to induce diabetes mellitus (DM). Autophagy was induced by two ways; rapamycin or fasting. The extent of autophagy and apoptosis were investigated by measuring the level of LC3B and p53 proteins, respectively, in pancreatic and kidney tissues using Western blotting (WB) technique and imaging the renal cells under transmission electron microscope. The efflux transporter P-glycoprotein was quantified by WB as well. Rapamycin-induced autophagy occurred concurrently with apoptosis. On the other hand, fasting supported P-glycoprotein recovery and renal cell survival together with disabling β-cells apoptosis. In conclusion, this study provides a potential link between rapamycin or fasting for the cross-regulation of apoptosis and autophagy in the setting of cell stress as DN. Unlike rapamycin, fasting enhanced the active expression of ABCB1 efflux protein, providing insights on the potential ameliorative effects of fasting in DN that require further elucidation.

Approximately 90% of diabetic males have varying degrees of testicular dysfunction. The current study investigates the possible beneficial consequences of ranolazine against T1DM-induced testicular dysfunction in rats. Thirty-two male Sprague Dawley rats were assorted into 4 groups; normal, diabetic (single 50 mg/kg STZ, I.P.) and ranolazine (40 and 80 mg/kg, orally). The present investigation revealed that the hypoglycemic impact of ranolazine significantly improved the testicular weight and body weight of the final rats, as well as the concentration of blood testosterone, sperm count, and viability, all of which were associated with STZ-induced testicular dysfunction. Furthermore, as demonstrated by elevated reduced glutathione (GSH) activity and lowered malondialdehyde (MDA) levels, diabetic rats administered ranolazine showed a noteworthy improvement in the oxidant/antioxidant ratio. Furthermore, a substantial rise in beclin-1 concentration was seen in conjunction with a significant decrease in thioredoxin-interacting protein (TXNIP) and interleukin-18 (IL-18) concentrations when ranolazine was administered. Although ranolazine exhibited a reduction in inflammation as seen by lower expression of nuclear factor-κB (NF-κB) and cluster of differentiation (CD68) in the testicles, these biochemical findings were validated by improvements in the morphological and histopathological outcomes of both the pancreatic and testicular tissues. In conclusion, daily oral administration of ranolazine (40 and 80 mg/kg) for 8 weeks could be a promising therapy for T1DM-induced testicular dysfunction through its dose-dependent anti-oxidant and anti-inflammatory effects. [Display omitted] • Ranolazine improved the testicular dysfunction in an experimental model of STZ-induced T1DM complication. • Ranolazine alleviated oxidative stress and inflammation associating with T1DM-induced testicular dysfunction. • Ranolazine showed preservation of morphological characteristics of the pancreatic β-cells and testicles. • Ranolazine induced autophagy and inhibited pyroptosis. [ABSTRACT FROM AUTHOR]

Diabetes is the most common endocrine disorder contributing to high morbidity and mortality globally. Due to the side effects reported for anti‐diabetic drugs, there is a rising interest in herbal medicine for diabetes mitigation. However, rare studies were performed to analyze the molecular effects of natural agents on diabetes. Therefore, this study is the first to assess the possible ameliorating effects of avocado and cinnamon extracts on streptozotocin (STZ)‐induced disturbances in the gene expression of PDX1 and Ins1 in type‐2 diabetic rats, in comparison to metformin. A total number of 50 male Albino rats were randomly divided into five groups; normal control, STZ‐induced diabetic group (65 mg/kg b.w divided into three doses 5 days apart), three other STZ‐diabetic groups were treated orally for 6 weeks with metformin (500 mg/kg b.w/day), an avocado fruit ethanolic extract (300 mg/kg b.w/day), or a cinnamon aqueous extract (200 mg/kg b.w/day). All rats were fasted overnight then euthanized, blood was collected, and serum was separated for biochemical analyses. The pancreas was processed for the evaluation of PDX1 and Ins1 gene expression by qRT‐PCR. Oral administration of the avocado/cinnamon extract significantly improved the altered levels of blood glucose, insulin, lipid profile, and total antioxidant capacity (TAC) and upregulated the pancreatic expression of PDX1 and Ins1 genes. In conclusion, this study added another mechanism of anti‐diabetic action for the plant extracts via upregulating the gene expression of PDX1 and Ins1 in STZ‐diabetic rats. Metformin has a more profound effect than the plant extracts; however, cinnamon has a comparable effect. Practical applications: Diabetes is a worldwide chronic serious problem; therefore, different efficacious drug treatments are currently available. However, several side effects of these drugs also negatively affect patient welfare. Therefore, the present study provides an additive/adjunct biochemical rationale for further natural intervention strategy for type‐2 diabetes through the introduction of plant‐derived products that revealed a wide range of therapeutic effects without causing untoward actions. This study revealed that cinnamon and avocado extracts exhibited marked anti‐diabetic and antioxidant effects in rats, as compared to the standard drug, metformin. These results augmented the previous ones and added a new molecular mechanism of action through upregulation of Ins1 and PDX1 in type‐2 diabetic rats. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the leading cause of dementia in humans, with a high social and economic cost. AD is predominantly a sporadic disease, and the intracerebroventricular (ICV) administration of streptozotocin (STZ) has been widely used as an AD-like model of dementia. While the etiology of AD remains unknown, changes such as glucose metabolism and activation of receptors for advanced glycation end products (RAGE) seem to underlie its pathogenesis. We hypothesized that methylglyoxal, an endogenous toxin derived from the glycolytic pathway, could be the precursor of advanced glycated end products that activates RAGE and that, consequently, may activate membrane NADPH oxidase (NOX), contributing to the inflammatory status of the model and the disease. We administered ICV-STZ to Wistar rats and evaluated several neurochemical parameters in the hippocampus, particularly glyoxalase 1 (GLO-1) activity, which serves as an index of high levels of methylglyoxal, and the contents of RAGE and NOX-2, the most abundant brain NOX isoform. At the times evaluated (4 and 24 weeks after STZ), we observed cognitive deficit, increased beta-amyloid content, and increased tau phosphorylation. A persistent increase in GLO-1 activity was found, as well as increases in RAGE and NOX-2 contents, suggesting astroglial and microglial commitment. The increase in NOX-2 may reflect elevated microglial activity (confirmed by IBA-1 marker), which may contribute to the synaptic dysfunction and pruning described in the literature, both in this model and AD patients. Furthermore, reinforcing this possibility, we found a reduction in cholinergic communication in the hippocampus (as shown by decreased choline acetyltransferase), a reduction in BDNF, and an increase in TGF-β, the combination of which may result in synaptic deterioration. [ABSTRACT FROM AUTHOR]

Diabetes refers to a group of metabolic disorders characterized by high blood glucose levels. Decreased zinc in the pancreas reduce the ability of the islet β-cells to produce insulin and exacerbate the oxidative stress-mediated complications of diabetes. Aim of work: Study the effect of nano-Zinc particles on glucose status,lipid profile,hepatic oxidative stress biomarkers in diabetic induced rats . 40 male albino rats, fresh and clean drinking water were supplied free access, housed together for 7 days for acclimatization, classified into four groups. Control: rats injected (I.P) with saline once weekly then saline orally 3 times / week. STZ: rats injected (I.P) with STZ solution at dose of 35mg/b.w. ZnONPs: rats recieved ZnoPs solution orally 3 timed / week for 8 weeks, STZ + ZnONPs: rats received a doses of ZnONPs and STZ solutions as we explained previously. Asignificant increase in FBS, HBA1C,MDA and total cholesterol (TC) in STZ group, increased in liver GSH in ZnONPs treated group (STZ+ZnONPs) and improvement of the results above in ZnONPs group. Conclusion: The protective impact of ZnONPs might be attributed to antioxidants, this led to improvement in the various investigated parameters; and it has a greater effect on preventing DM disease. [ABSTRACT FROM AUTHOR]

Background and objectives: Cardiac apoptosis is one of the most important cardiovascular complications of diabetes. We aimed to investigate the changes of Bax, Bcl2 and caspase 3 in cardiac tissue of diabetic rats after six weeks aerobic exercise. Methods: Thirty two male Wistar rats were randomly divided into healthy control, diabetes control and diabetes + exercise groups. Diabetes was induced by intraperitoneal injection of streptozotocin solution (55 mg/kg). Two weeks after the injection, fasting blood glucose levels were measured to confirm induction of diabetes. The exercise program was performed five days a week for six weeks. Variables were evaluated by ELISA and western blot analysis. All statistical analyses were performed in SPSS (version 22) using ANOVA and at significance of 0.05. Results: The induction of diabetes in the control groups resulted in a significant increase in Bax, Bax/Bcl2 ratio and a significant decrease in Bcl2 levels (P=0.024). The six-week training exercise in diabetic groups significantly decreased Bax and Bax/Bcl2 ratio and significantly increased Bcl2 (P=0.018). Conclusion: Our finding showed that diabetes could increase apoptosis in cardiac tissue. In addition, the six-week aerobic exercise can be used as a non-pharmacological strategy to reduce diabetes-related apoptosis in cardiomyocytes.

Type 1 diabetes mellitus (T1DM) patients have osteopenia and impaired fracture healing due to decreased osteoblast activity. Further, no adequate treatments are currently available that can restore impaired healing in T1DM; hence a significant need exists to investigate new therapeutics for treatment of orthopedic complications. Sclerostin (SOST), a WNT antagonist, negatively regulates bone formation, and SostAb is a potent bone anabolic agent. To determine whether SOST antibody (SostAb) treatment improves fracture healing in streptozotocin (STZ) induced T1DM mice, we administered SostAb twice weekly for up to 21days post-fracture, and examined bone quality and callus outcomes at 21days and 42days post-fracture (11 and 14weeks of age, respectively). Here we show that SostAb treatment improves bone parameters; these improvements persist after cessation of antibody treatment. Markers of osteoblast differentiation such as Runx2, collagen I, osteocalcin, and DMP1 were reduced, while an abundant number of SP7/osterix-positive early osteoblasts were observed on the bone surface of STZ calluses. These results suggest that STZ calluses have poor osteogenesis resulting from failure of osteoblasts to fully differentiate and produce mineralized matrix, which produces a less mineralized callus. SostAb treatment enhanced fracture healing in both normal and STZ groups, and in STZ+SostAb mice, also reversed the lower mineralization seen in STZ calluses. Micro-CT analysis of calluses revealed improved bone parameters with SostAb treatment, and the mineralized bone was comparable to Controls. Additionally, we found sclerostin levels to be elevated in STZ mice and β-catenin activity to be reduced. Consistent with its function as a WNT antagonist, SostAb treatment enhanced β-catenin activity, but also increased the levels of SOST in the callus and in circulation. Our results indicate that SostAb treatment rescues the impaired osteogenesis seen in the STZ induced T1DM fracture model by facilitating osteoblast differentiation and mineralization of bone.

Diabetic retinopathy (DR) is the most common microvascular complication in diabetes and the leading cause of vision loss and blindness globally. Due to the unsatisfied outcome of current therapies, a novel strategy needs to be developed. BV2 microglial cells were treated with 25 natural compounds, respectively, stimulated by high glucose (HG) to screen for a potential candidate drug. Streptozotocin (STZ)-induced diabetic mice were injected with different doses of the candidate sesamin every 2 days for 1 mo. Then, its protective role and possible mechanism were evaluated. Sesamin was selected as the candidate drug due to its inhibition on the secretion of tumor necrosis factor-α (TNFα) in the screen assay. Sesamin also dose-dependently inhibited mRNA levels of HG-induced inflammatory cytokines, including TNFα, interleukin (IL)-1b, and IL-6, activated NF-κB signaling pathway, and reduced oxidative stress by decreasing reactive oxygen species levels and increasing antioxidant enzymes in the BV2 and primary retinal microglia. In addition, sesamin alleviated brain-retinal barrier breakdown by Evans blue leakage assay and reduced inflammation in streptozotocin-induced diabetic mice. In conclusion, sesamin effectively inhibits HG-induced microglial inflammation in the retina both in vivo and in vitro, suggesting that sesamin might serve as a candidate drug for DR treatment. NEW & NOTEWORTHY Sesamin effectively inhibits HG-induced microglial inflammation in the retina both in vivo and in vitro, which suggests that sesamin might serve as a candidate drug for diabetic retinopathy treatment. [ABSTRACT FROM AUTHOR]

Streptozotocin (STZ) is a cytostatic antibiotic produced by Streptomyces achromogenes. It is an inhibitor of DNA replication showing a special affinity for pancreatic β-cells DNA. It is used in medicine as an antineoplastic agent (indicated in the treatment of malignant neoplasms of pancreas) and in scientific research to induce hyperglycemia, insulitis, diabetes mellitus (DM), Alzheimer’s disease on experimental animals. Insulinopenia syndrome is called ‘streptozotocin diabetes’, caused by necrosis of the pancreatic β-cells. STZ induced DM offers a very cost-effective and expeditious technique in medical research.

Abstract Backgrounds Streptozotocin (STZ)‐ induced diabetic monkey is a wide used preclinical animal model for the investigation of diabetes such as islet transplantation and development of diabetic drugs. There are serious side effects of this method, including nausea, emesis, weight loss, liver damage, renal failure, and metabolic acidosis. In order to reduce the side effects, diabetic monkeys were induced using clinical‐grade STZ. However, clinical‐grade STZ is not available in China. Here, we establised a method by using 100 mg/kg analytical‐grade STZ to induce complete diabetes in cynomolgus monkey without generating adverse effects to liver and renal. Methods Three cynomolgus monkeys were used in this study. 100 mg/kg STZ dissolved in normal saline and infused through vein line in 5 minutes after indwelling catheter in the carotid artery and jugular vein. After the STZ administration, blood glucose levels were examined every 1 or 2 hours in the first 48 hours. Then, blood glucose levels were examined twice per day during the first week after the STZ injection. Insulin and C‐peptide levels were measured by ELISA. Blood chemistry of hepatic and renal function tests were performed. Insulin and glucagon expression in the islet of diabetic monkey and normal monkey were examined by immunohistochemistry assays. Results The stimulated C‐peptide level (Intravenous glucose tolerance test) which is less than 0.5 ng/mL, the triphasic blood glucose response and the destroyed β cell suggested the complete induction of diabetes model. No apparent adverse effects were observed including no signs of vomiting and toxicity after STZ injection. Conclusion In summary, we established a safe and reproducible STZ‐induced diabetic cynomolgus monkey model for islet transplantation which will be used to develop novel approaches for the treatment of diabetes.

Objectives: Aqueous extracts of Rhizophora mucronata and Avicennia marina leaves were inves¬tigated for their hepatoprotective potential in diabetic rats. Materials and methods: One hundred twenty male albino rats were randomly assigned to eight equal groups (n = 15). The first group (control) comprised normal healthy rats, while the second to fifth groups were intraperitoneally injected with a single dose of streptozotocin (STZ) [60 mg/ kg body weight (BW)] for induction of diabetes. Group 2 was kept as positive diabetic control, while groups 35 were orally treated with aqueous extracts of R. mucronata (400 mg/kg BW), A. marina (400 mg/kg BW) and with a combination of ½ a dose of the two plants, respectively, for six weeks. Groups 68 were non-diabetic rats that orally received aqueous extracts of R. mucronata (400 mg/kg BW), A. marina (400 mg/kg BW), and a combination of ½ a dose of the two plants, respectively, for 6 weeks. Results: STZ-induced diabetic rats showed a significant reduction in serum glucose and liver enzymes, increased serum insulin, Homeostasis Model Assessment of β-cells (HOMA-β), and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Histopathological and immuno¬histochemical examinations of the liver revealed improved pathologic criteria in the plant extract treated diabetic rats compared with the remarkable changes which had been seen in STZ-induced diabetic rats. Conclusion: This study suggests that the aqueous extract of R. mucronata or its combination with A. marina showed potent hypoglycemic and hepatoprotective effects for liver dysfunction, as well as histopathological and immunohistochemical changes in the liver of STZ-induced diabetic rats. [J Adv Vet Anim Res 2020; 7(1.000): 177-185]