Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

Background: Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are accurately detected late in the progressive form of the disease. Methods: Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. Results: In the apparently macroscopically unchanged tegument, photon microscopy revealed both progressive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. Conclusions: The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

With the increasing resistance of bacteria to current antibiotics, novel compounds are urgently needed to treat bacterial infections. Streptozotocin (STZ) is a natural product that has broad-spectrum antibiotic activity, albeit with limited use because of its toxicity to pancreatic β cells. In an attempt to derivatize STZ through structural modification at the C3 position, we performed the synthesis of three novel STZ analogues by making use of our recently developed regioselective oxidation protocol. Keto-STZ (2) shows the highest inhibition of bacterial growth (MIC and viability assays), but is also the most cytotoxic compound. Pre-sensitizing the bacteria with GlcNAc increased the antimicrobial effect, but did not result in complete killing. Interestingly, allo-STZ (3) revealed moderate concentration-dependent antimicrobial activity and no cytotoxicity towards β cells, and deoxy-STZ (4) showed no activity at all.

The production of nanoparticles enhances the bioactivity of biological molecules for drug delivery to infection sites. This study explains how silver nanoparticles (AgNPs) coating enhanced the hypoglycemic effects of vanillic acid in male diabetic rats with diabetes brought on by streptozotocin. (STZ). Four groups of 24 rats were created for the investigation and divided into them. The first group rats (G1; untreated) were given a basal diet, whereas the other three groups all developed diabetes through STZ injection. Diabetic rats who were not getting therapy were included in the second group (G2; STZ-positive), whereas the other diabetic rats were divided into the third group (G3, vanillic acid-treated) and the fourth group (G4; AgNPs-coated vanillic acid treated). The treatment lasted four weeks. In G2, the induction of diabetes led to an increase in serum glucose, glycated proteins, renal indices, interleukin-6 (IL-6), K+, immunoglobulins, and lipid peroxidation, while decreased Ca++, Na+, and other antioxidants in the kidney tissue homogenate. In addition, aberrant signs were present in the pancreas and kidneys of diabetic rats. The renal and pancreatic tissues were effectively enhanced by vanillic acid or vanillic acid-coated AgNPs, bringing them very close to their pre-diabetic conditions. AgNPs-coated vanillic acid offered a stronger defense against STZ-induced diabetes and lessened the effects of hyperglycemia compared to ordinary vanillic acid. Additionally, using vanillic acid coated with silver nanoparticles greatly reduced inflammation when compared to using vanillic acid alone. This outcome suggests increased antioxidant activity.

The anti-oxidative stress and anti-inflammatory effects of natural products can prevent diabetic complications such as retinopathy, nephropathy, neuropathy, and blood vessel damage. Fucoxanthin has potent antioxidant and anti-inflammatory properties. This research aimed to examine the preventative effects of fucoxanthin nanoparticles against aortic damage in diabetic rats. Dynamic Light Scattering (DLS) was utilized to identify the size of fucoxanthin nanoparticles. The experiment consisted of five groups (n=8) namely: Rats only received Streptozotocin (STZ) solvent and fucoxanthin nanoparticles solvent as a control group; Rats only received STZ and solvent of fucoxanthin nanoparticles solvent as the diabetic group; and Rats received STZ and fucoxanthine nanoparticles at a dose of 75, 150 and 300 mg/Kg BW as fucoxanthin nanoparticle group. The fucoxanthin nanoparticle sizes were 217.2 ± 42.8 nm in DLS. The dose-dependent administration of fucoxanthin nanoparticles elevated significant superoxide dismutase (SOD), glutathione peroxidase (GPx), nitric oxide (NO), endothelial nitric oxide synthase (eNOS), and insulin. However, blood glucose, malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and endothelial cell necrosis decreased compared to those in the streptozotocin group. Our findings suggest that fucoxanthin nanoparticles decrease malondialdehyde levels and increase superoxide dismutase and glutathione peroxidase levels to inhibit oxidative stress, consequently preventing diabetes-induced aortic damage. Furthermore, fucoxanthin nanoparticles also may inhibit inflammation by reducing IL-6 and TNF-α levels. These mechanisms reduce endothelial cell necrosis, which can increase the expression of eNOS and NO levels in the aorta of diabetic rats.

Mangifera indica (mango), a member of the Anacardiaceae family, is renowned for its diverse pharmacological properties, encompassing antidiabetic, antioxidant, antiviral, cardiotonic, hypotensive, and anti-inflammatory effects. The present study delves the insulin-releasing and glucose-lowering potential of the ethanolic extract of Mangifera indica (EEMI) leaves in streptozotocin (STZ)-induced type 2 diabetic rats, concurrently investigating its phytoconstituents. EEMI's effects on insulin secretion were measured using BRIN BD11 β-cells and isolated mouse islets. It’s enzymatic inhibitory properties on carbohydrate digestion, glucose absorption, and free radicals were investigated using starch digestion, glucose diffusion and DPPH assay methods. In-vivo parameters including lipid profile and liver glycogen content were assessed on streptozotocin-induced type 2 diabetic rats. EEMI exhibited a dose-dependent increase in insulin secretion from clonal pancreatic BRIN BD11 β-cells and isolated mouse islets. EEMI inhibited starch digestion, glucose diffusion over time and DPPH activity in vitro. In acute in vivo studies, EEMI improved food intake, oral glucose tolerance. Moreover, following 28 days of treatment with EEMI, a remarkable amelioration in body weight, fasting blood glucose, plasma insulin, liver glycogen content, total cholesterol, triglyceride, LDL, VLDL and HDL levels were observed. Further phytochemical analysis with EEMI identified the presence of alkaloids, tannins, saponins, steroids, glycosides, flavonoids, and reducing sugar. The synergistic effects of EEMI, potentially attributable to naturally occurring phytoconstituents, hold promise for the development of enriched antidiabetic therapies, offering a promising avenue for the management of type 2 diabetes.

The anti-oxidative stress and anti-inflammatory effects of natural products can prevent diabetic complications such as retinopathy, nephropathy, neuropathy, and blood vessel damage. Fucoxanthin has potent antioxidant and anti-inflammatory properties. This research aimed to examine the preventative effects of fucoxanthin nanoparticles against aortic damage in diabetic rats. Dynamic Light Scattering (DLS) was utilized to identify the size of fucoxanthin nanoparticles. The experiment consisted of five groups (n=8) namely: rats only received streptozotocin (STZ) solvent and fucoxanthin nanoparticles solvent as a control group; rats only received STZ and solvent of fucoxanthin nanoparticles solvent as the diabetic group; and rats received STZ and fucoxanthin nanoparticles at a dose of 75, 150 and 300 mg/kg BW as the fucoxanthin nanoparticle group. The fucoxanthin nanoparticle sizes were 217.2 ± 42.8 nm in DLS. The dose-dependent administration of fucoxanthin nanoparticles elevated significant superoxide dismutase (SOD), glutathione peroxidase (GPx), nitric oxide (NO), endothelial nitric oxide synthase (eNOS), and insulin. However, blood glucose, malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and endothelial cell necrosis decreased compared to those in the streptozotocin group. Our findings suggest that fucoxanthin nanoparticles decrease malondialdehyde levels and increase superoxide dismutase and glutathione peroxidase levels to inhibit oxidative stress, consequently preventing diabetes-induced aortic damage. Furthermore, fucoxanthin nanoparticles also may inhibit inflammation by reducing IL-6 and TNF-α levels. These mechanisms reduce endothelial cell necrosis, which can increase the expression of eNOS and NO levels in the aorta of diabetic rats.

Alzheimer’s disease (AD) is an age-related neuropsychiatric disorder and a common cause of progressive dementia. Diltiazem (DTZ), the non-dihydropyridine benzothiazepine class of calcium channel blocker (CCB), used clinically in angina and other cardiovascular disorders have proven neurological benefits. In the present study, the neuroprotective anti-dementia effects of DTZ against intra-cerebroventricular-streptozotocin (ICV-STZ)-induced sporadic AD (SAD)-type rat model was investigated. ICV-STZ-induced cognitive impairments were measured by passive avoidance and Morris water maze tasks. Anti-oxidative enzyme status, pro-inflammatory markers, and amyloid-beta (Aβ) protein expression in rat brain tissues were measured by ELISA kits, Western blotting, and immunostaining techniques. Data revealed that ICV-STZ injection in rats significantly induced cognitive deficits and altered the levels of oxidative and pro-inflammatory markers (p < 0.05 ~ p < 0.001). Treatment with DTZ (10 mg/kg, 20 mg/kg, and 40 mg/kg. p.o.) daily for twenty-one days, 1 h before a single ICV-STZ (3 mg/kg) injection, significantly improved cognitive impairments, ameliorated the ICV-STZ-induced altered nitrite, pro-inflammatory cytokines (TNF-α, and IL-1β) and anti-oxidative enzyme levels (superoxide dismutase, lipid peroxidation, and glutathione). Further, DTZ restored the increased Aβ protein expression in ICV-STZ-induced brain tissue Considering the data obtained, DTZ exhibited a potential neuroprotective anti-dementia role in ICV-STZ-induced SAD-type conditions in rats and might be repurposed as a potential therapeutic agent in the treatment and management of AD and related dementia pathologies.

Diabetes is a group of diseases characterized by loss of β cell mass and/or -function, resulting in hyperglycemia. Approx. 537 million people worldwide suffer from diabetes – a number which is expected to increase. Diabetes is primarily treated by exogenous insulin, which comes with the challenges of maintaining glycemic control to prevent ketoacidosis and severe complications. The need for a curative treatment has initiated the research in β cell regeneration. Several studies in mice have identified essential genes for β cell fate, which can be manipulated in other cells to induce generation of new β cells. Zebrafish, a regeneration-positive animal model, has shown several different sources of new β cells, including regeneration by self-replication, neogenesis by duct-associated progenitor cells, and transdifferentiation of other endocrine islet cells. The animal models used in this research area are either limited by their low regenerative ability (mice), or their small size and remoteness from humans (zebrafish). There is a need for new animal models of diabetes, in which the molecular pathways of endogenous regeneration can be studied. This study proposes the axolotl salamander (Ambystoma mexicanum) as a model for studying the regeneration of β cells. The axolotl has shown great regenerative capability, as they have proven capable of regenerating amputated limbs, and hearts with myocardial infarction, among other organs. This study aims to establish a diabetic axolotl model, investigate their regenerative ability in the pancreas, and examine the potential systemic effects of the induced disease. In a pilot study, five different protocols using STZ (streptozotocin) were tested, and the most optimal protocol was found. Furthermore, the glucose tolerance test was optimized to characterize the glycemic state of the animals. The effect of the treatment on blood glucose levels was measured to characterize the development and decline of the disease. The histological changes in the pancreas were examined. Moreover, the systemic effects of the STZ treatment were investigated in blood and urine. The study indicated that it is possible to induce diabetes in the axolotl, but variations between the animals should be minimized, or the sample size should be increased to conduct a satisfying experiment, as it was not possible to induce diabetes in all animals. Regeneration was not observed histologically, but a restoration of blood glucose levels was seen over the span of the experiment. Lastly, edema formation was observed in some of the STZ-treated animals, but the cause of edema remains undetermined.

The prevalence of diabetes mellitus (DM) continues to rise globally, posing significant health challenges and burdens. This metabolic disorder, characterized by elevated blood glucose levels, contributes to various complications including cardiovascular diseases, kidney failure, and stroke. While conventional diabetic drugs exist, they often come with adverse side effects, necessitating the exploration of safer and more cost-effective alternatives, particularly from natural sources like medicinal plants. This study investigates the potential of Neocarya macrophylla (Nm) Ethyl acetate leaf fraction in managing DM. Utilizing a high-fat diet/streptozotocin-induced diabetic rat model, the study explores several key aspects including effective dose determination, biological activity, impact on body mass index (BMI), and complete blood count. Statistical analysis was conducted using GraphPad Prism version 9.1. The determination of the minimum effective dose reveals that 120mg/kg of Ethyl acetate fraction of Nm reduced the blood glucose by 28.9% after 4 hours. In addition, ethyl acetate fraction (120 mg/kg) possessed the most hypoglycemic activity compared to the other fractions of Nm. The Ethyl acetate fraction of Nm at 120mg/kg significantly reduced fasting blood glucose levels compared to the diabetic control(p=0.001) and slightly decreased BMI. Furthermore, the fraction demonstrated significant improvement in the parameters of some of the blood count indices such as red blood cells (p<0.001), total white cells (p<0.01) and platelet (p<0.001) compared to the diabetic control. These findings underscore the potential of Nm as a holistic therapeutic option for managing DM and its haematological complications. In conclusion, this study sheds light on the hypoglycemic potential of Nm Ethyl acetate leaf fraction, offering valuable insights into its effectiveness, safety, and broader physiological impacts. Further research into the mechanisms underlying its therapeutic effects is warranted to fully harness its therapeutic potential in diabetes management.