Animal Models Of Diabetes Research Articles

Potent anti-inflammatory and anti-apoptotic activities of electrostatically complexed C-peptide nanospheres ameliorate diabetic nephropathy

In the present era of “Diabetic Pandemic”, peptide-based therapies have generated immense interest however, are facing odds due to inevitable limitations like stability, delivery complications and off-target effects. One such promising molecule is C-peptide (CPep, 31 amino acid polypeptide with t1/2 30 min); it is a cleaved subunit of pro-insulin, well known to suppress microvascular complications in kidney but has not been able to undergo translation to the clinic till date. Herein, a polymeric CPep nano-complexes (NPX) was prepared by leveraging electrostatic interaction between in-house synthesized cationic, polyethylene carbonate (PEC) based copolymer (Mol. wt. 44,767 Da) and negatively charged CPep (Mol. wt. 3299 Da) at pH 7.4 and further evaluated in vitro and in vivo. NPX exhibited a spherical morphology with a particle size of 167 nm and zeta potential equivalent to +10.3, with 85.70 % of CPep complexation efficiency. The cellular uptake of FITC-tagged CPep NPX was 95.61 % in normal rat kidney cells, NRK-52E. Additionally, the hemocompatible NPX showed prominent cell-proliferative, anti-oxidative (1.8 folds increased GSH; 2.8 folds reduced nitrite concentration) and anti-inflammatory activity in metabolic stress induced NRK-52E cells as well. The observation was further confirmed by upregulation of anti-apoptotic protein BCl2 by 3.5 folds, and proliferative markers (β1-integrin and EGFR) by 3.5 and 2.3 folds, respectively, compared to the high glucose treated control group. Pharmacokinetic study of NPX in Wistar rats revealed a 6.34 folds greater half-life than free CPep. In in-vivo efficacy study in STZ-induced diabetic nephropathy animal model, NPX reduced blood glucose levels and IL-6 levels significantly by 1.3 and 2.5 folds, respectively, as compared to the disease control group. The above findings suggested that NPX has tremendous potential to impart sustained release of CPep, resulting in enhanced efficacy to treat diabetes-induced nephropathy and significantly improved renal pathology.

Anti-hyperglycemic Activity of the Piper longum Dried Fruit Extract on the Experimental Animal Model

Predominately, in the Indian tradition, the species Piper longum could play a significant role in the management of several severe disorders such as asthma, tuberculosis, rheumatism, and epilepsy. Mostly, the plant root would be responsible for treating insomnia, rheumatism, and epilepsy, as well as plant leaves for a prevailing stimulant for both the digestive and the respiratory systems. The alcoholic extract of P. longum fruits showed antiamoebic, anti-inflammatory, and immunomodulatory potential in experimental animals. In addition to these benefits, the current study concluded that the examination of the ethanolic extract of P. longum fruits as an anti-hyperglycemic in streptozotocin (STZ)-induced diabetic animal model (Wistar rats). A diabetic condition could be induced in an animal model by dissolving STZ in a 0.1 M citrate buffer of pH 4.5. It was injected intraperitoneally at a dose of 50 mg/kg body weight in the animal test model. All the test animals were fed with a 5% dextrose solution to control overnight hypoglycemic conditions. Subsequently, 48 hours of hyperglycemic test animals were selected for the study. The observed anti-hyperglycemic effect of ethanolic extract of P. longum dried fruits should correspond to that of the reference standard, i.e., glibenclamide. The study reveals that the ethanolic extract of P. longum fruits has a promising potential as an anti-hyperglycemic in the STZ-induced diabetic animal test model. So, it is presumed that the ethanolic extract of P. longum could be a promising alternative for severe diabetes complications such as hyperglycemia, oxidative stress, etc., in the near future

Protective Effect of Oleuropein on Memory Impairment and Oxidative Stress in Streptozotocin -Induced Diabetes Rats via Modulation of NF -kB and Nrf-2 Pathways

Background & Objectives: Diabetes is the most common metabolic disease which is associated with hyperglycemia and long -term complications. This study aimed to elucidate the anti -diabetic role of oleuropein (OLE) in a streptozotocin (STZ) -induced diabetic animal model. Materials & Methods: Adult male Wistar rats (200 –250 g) were randomly divided into four groups: 1) Control group, 2) STZ group: diabetic rats that received STZ (60 mg/kg), 3) OLE 50 group: diabetic rats treated with oral OLE at 50 mg/kg of body weight daily for 28 days, and 4) OLE 100 group: diabetic rats treated with oral OLE at 100 mg/kg of body weight daily for 28 days. Memory function and biochemical factors such as malondialdehyde (MDA) levels, glutathione peroxidase (GPx), and total thiol activity were evaluated in the rats' cerebral cortex and striatum tissues. Moreover, nuclear transcription factor -kappa B (NF - κB) and nuclear factor E2 -related factor 2 (Nrf2) pathway s activation were determined in cerebral cortex and striatum tissues by real -time polymerase chain reaction (RT -PCR). Results: Chronic administration of OLE ameliorated cognitive deficits and attenuated oxidative stress induced by diabetes. Additionally, OLE significantly prohibited the activation of the pro -inflammatory marker NF - κB and downregulated Nrf2 expression in STZ -induced diabetic rats. Conclusion : Our results confirm the significant protective role of OLE against STZ -induced diabetes in rats by up -regulating Nrf2 signaling and enhancing antioxidant activity.

Lipids balance as a spectroscopy marker of diabetes. Analysis of FTIR spectra by 2D correlation and machine learning analyses

The number of people suffering from type 2 diabetes has rapidly increased. Taking into account, that elevated intracellular lipid concentrations, as well as their metabolism, are correlated with diminished insulin sensitivity, in this study we would like to show lipids spectroscopy markers of diabetes. For this purpose, serum collected from rats (animal model of diabetes) was analyzed using Fourier Transformed Infrared-Attenuated Total Reflection (FTIR-ATR) spectroscopy. Analyzed spectra showed that rats with diabetes presented higher concentration of phospholipids and cholesterol in comparison with non-diabetic rats. Moreover, the analysis of second (IInd) derivative spectra showed no structural changes in lipids. Machine learning methods showed higher accuracy for IInd derivative spectra (from 65 % to 89 %) than for absorbance FTIR spectra (53–65 %). Moreover, it was possible to identify significant wavelength intervals from IInd derivative spectra using random forest-based feature selection algorithm, which further increased the accuracy of the classification (up to 92 % for phospholipid region). Moreover decision tree based on the selected features showed, that peaks at 1016 cm−1 and 2936 cm−1 can be good candidates of lipids marker of diabetes.

Stimulated Full-Thickness Cutaneous Wound Healing with Bioactive Dressings of Zinc and Cobalt Ion-Doped Bioactive Glass-Coated Eggshell Membranes in a Diabetic Rabbit Model.

Eggshell membrane-based biomedical applications have recently received great attention for their wound-healing properties. However, there are limited studies on diabetic wound healing. In this regard, we devised four types of composite eggshell membrane mats with nanoscale coatings of bioactive glass/Zn/Co-doped bioactive glass (ESM + BAG, ESM + ZnBAG, ESM + CoBAG, and ESM + ZnCoBAG) as wound-dressing materials for chronic nonhealing diabetic wounds. A detailed study of the physicochemical properties of the mats was conducted. In vitro studies demonstrated cytocompatibility and viability of human dermal fibroblasts on all four types of mats. The cells also attached finely on the mats with the help of cellular extensions, as evident from scanning electron microscopy (SEM) and rhodamine-phalloidin and Hoechst 33342 staining of cellular components. Endowed with bioactive properties, these mats influenced all aspects of full-thickness skin wound healing in diabetic animal model studies. All of the mats, especially the ESM + ZnCoBAG mat, showed the earliest wound closure, effective renewal, and restructuring of the extracellular matrix in terms of an accurate and timely accumulation of collagen, elastin, and reticulin fibers. Hydroxyproline and sulfated glycosaminoglycans were significantly (p < 0.01, p < 0.05) higher in ESM-ZnCoBAG-treated wounds in comparison to ESM-BAG-treated wounds, which suggests that these newly developed mats have potential as an affordable diabetic wound care solution in biomedical research.

#1870 Uninephrectomized diabetic rats delay onset of hyperglycemia via down-regulation of SGLT2 mRNA

Abstract Background and Aims The kidney is essential for glucose metabolism. Reabsorption of almost all the glucose filtered by the glomerulus is performed by the sodium-glucose cotransporters (the SGLTs) in the proximal tubules, with SGLT2 responsible for about 90%. In addition, the kidney, along with the liver, plays an important role in gluconeogenesis, especially in the long fasting state. SGLT2 inhibitors originally developed for the treatment of type 2 diabetes mellitus (DM) are clinically very effective drugs halting chronic kidney disease progression. The underlying mechanisms are, however, not fully understood. Furthermore, SGLT2 expression in diabetic patients has been reported to increase and decrease but remains unclear. Therefore, this study aimed to evaluate how uninephrectomy (UNx) and SGLT2 inhibitor treatment affects the dynamics of blood glucose and SGLTs in SDT fatty rats with obese type 2 DM (leptin receptor mutation), which is hyperglycemic from an early stage. Method 24 male SDT fatty rats were divided into four groups: sham + placebo group (n=6); sham + dapagliflozin (dapa, 1.5 mg/kg/day) group (n=6); UNx + placebo group (n=6); UNx + dapa group (n=6). UNx or sham operations were undergone at week 6. Measurements included body weight, food intake, water consumption, urine output, blood pressure, serum creatinine, and blood glucose in the experiment. At week 12, the rats were sacrificed, and the kidneys were sampled to measure SGLT1 and SGLT2 mRNA in the renal cortex by real-time PCR quantification. Results Blood glucose levels continued to rise from week 7 in the sham + placebo group, but the rate of increase was still slower in the UNx + placebo group, and the increase in blood glucose levels was mostly suppressed with dapa administration (Fig. 1). Only the Sham + placebo group showed increased urinary volume and weight loss after week 10 due to hyperglycemia. There were no significant differences in serum creatinine or blood pressure during the study. Real-time PCR results showed that SGLT2 mRNA in the renal cortex was significantly decreased by 26% in the UNx group (P=0.0386), but SGLT1 mRNA was not significantly different. Conclusion Uninephrectomized diabetic rats delayed onset of hyperglycemia and reduced SGLT2 mRNA; SGLT2 inhibitor treatment further delayed the onset of hyperglycemia but did not alter SGLT2 mRNA expression. In animal models of diabetes, renal glucose reabsorption appeared to be a major contributor to the development of hyperglycemia.

Effect of Barley (Hordeum vulgare) on Renal Function in a Diabetic Animal Model: A Study in Experimental Rats

Effect of Barley (Hordeum vulgare) on Renal Function in a Diabetic Animal Model: A Study in Experimental Rats

Dynamic hydrogel-integrated microneedle patch with extracellular vesicles encapsulation for wound healing

Excessive reactive oxygen species (ROS) generated by wounds and bacterial infection are the great obstacles for diabetic wound closure. Here, we present a novel dual ROS-scavenging and antibacterial microneedle array patch with M2 macrophage-derived extracellular vesicles (M2-EVs) encapsulation for diabetic wound healing. The microneedle patch with a core–shell structure is composed of hyaluronic acid (HA) and PFP hydrogel crosslinked by polyvinyl alcohol (PVA)/2-formylphenylboronic acid (2-FPBA)/polyetherimide (PEI). When exposed to high levels of ROS existed in the wound, the dynamic covalent bonds of the hydrogel network can dissociate and subsequently release M2-EVs from the HA core. Benefitting from ROS-scavenging properties, antibacterial activities, and macrophage polarization driven by M2-EVs, the microneedle patch could effectively promote wound closure in diabetic animal models. These results indicated that the proposed ROS-scavenging microneedle patches with EVs delivery are promising for variety of difficult-to-heal wounds in clinical application.

Topical naltrexone increases aquaporin 5 production in the lacrimal gland and restores tear production in diabetic rats.

Diabetes mellitus is a prevalent disease that is often accompanied by ocular surface abnormalities including delayed epithelial wound healing and decreased corneal sensitivity. The impact of diabetes on the lacrimal functional unit (LFU) and the structures responsible for maintaining tear homeostasis, is not completely known. It has been shown that the Opioid Growth Factor Receptor (OGFr), and its ligand, Opioid Growth Factor (OGF), is dysregulated in the ocular surface of diabetic rats leading to overproduction of the inhibitory growth peptide OGF. The opioid antagonist naltrexone hydrochloride (NTX) blocks the OGF-OGFr pathway, and complete blockade following systemic or topical treatment with NTX restores the rate of re-epithelialization of corneal epithelial wounds, normalizes corneal sensitivity, and reverses dry eye in diabetic animal models. These effects occur rapidly and within days of initiating treatment. The present study was designed to understand mechanisms related to the fast reversal (<5 days) of dry eye by NTX in type 1 diabetes (T1D) by investigating dysregulation of the LFU. The approach involved examination of the morphology of the LFU before and after NTX treatment. Male and female adult Sprague-Dawley rats were rendered hyperglycemic with streptozotocin, and after 6 weeks rats were considered to be a T1D model. Rats received topical NTX twice daily to one eye for 10 days. During the period of treatment, tear production and corneal sensitivity were recorded. On day 11, animals were euthanized and orbital tissues including conjunctiva, eyelids, and lacrimal glands, were removed and processed for histologic examination including immunohistochemistry. Male and female T1D rats had significantly decreased tear production and corneal insensitivity, significantly decreased number and size of lacrimal gland acini, decreased expression of aquaporin-5 (AQP5) protein and decreased goblet cell size. Thus, 10 days of NTX treatment restored tear production and corneal sensitivity to normal values, increased AQP5 expression, and restored the surface area of goblet cells to normal. NTX had no effect on the number of lacrimal gland acini or the number of conjunctival goblet cells. In summary, blockade of the OGF-OGFr pathway with NTX reversed corneal and lacrimal gland complications and restored some components of tear homeostasis confirming the efficacy of topical NTX as a treatment for ocular defects in diabetes.

The Effect of a High-Fat Western Diet on Diabetic Nephropathy and the Pathogenesis of Type 2 Diabetes

The high-fat Western diet is a key contributor to the growing rate of obesity, which has become a global health concern. Additionally, obesity increases the risk of developing metabolic syndrome which leads to a range of chronic illnesses like diabetes, heart disease, and stroke. Diabetic Nephropathy (DN) is a complication prevalent in one-third of people with Type 2 Diabetes and leads to End Stage Renal Disease. The aim of this study was to assess how a high-fat Western diet impacts diabetic severity and renal, cardiovascular, and hepatic injury, in a rodent model of type 2 Diabetes. We used aged (&gt;38 weeks old, with severe renal disease) and young (12 weeks old, prior to major kidney damage) male and female Type 2 Diabetic Nephropathy (T2DN) rats, a non-obese diabetic animal model, and placed them on either normal (NFD) or high fat (HFD) calorically balanced diets for 12 weeks. Urine sampling and glucose tolerance tests (GTT) were assessed every 3 weeks. All rats on the HFD had significantly increased total body weights (TBW). However, average caloric intake over the 12 weeks was not significantly different in young males and females or in old males, while the aged HFD females had a significant increase (52.18 ± 1.536 vs 67.43 ± 0.4682 kcal/g, p=0.0001). The HFD had no effect on female GTT curves or fasting blood glucose in either age group. In contrast, the HFD males’ glucose intolerance and fasting blood glucose levels increased progressively and became significantly different between diets by week 9 (old: 204.5 ± 10.8 vs 284.4 ± 15.8 mg/dL, p=0.003, young: 193.3 ± 9.497 vs 257.5 ± 17.19 mg/dL, p=0.02). The HFD did not affect urine output or 2-kidney/TBW ratios in both sexes, while heart weight/TBW ratios in females were significantly reduced on the HFD in both age groups. Studies are ongoing in young animals; however, old animals revealed a significant increase in lipid deposits in the liver of HFD group for both males and females. There were no significant changes in circulating cholesterol and triglyceride levels between diets; however, there was a trend to increased triglycerides in females on HFD (p=0.051). The liver function panel showed a significant increase in ALP liver enzyme in the HFD group of both sexes. Picrosirius red-stained heart tissue showed increased fibrosis in the HFD aged males. Microbiome analysis revealed a significant decrease in gut microbiota alpha diversity in males on HFD, while no significant changes were observed in females between diets. Ongoing studies will quantify renal damage, including cortical fibrosis, medullary protein casts, glomerular damage, albuminuria, and KIM-1 staining, as well as lipidemia and heart fibrosis resulting from the HFD for both old and young animals. In conclusion, the HFD appears to have a more deleterious effect on glucose handling in both old and young T2DN males than in female rats; however, further studies are warranted to validate this effect. R01 DK129227, R01 DK135644, R00 HL153686. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Oxidative Stress, Endothelial Dysfunction, and N-Acetylcysteine in Type 2 Diabetes Mellitus.

Significance: Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality globally. Endothelial dysfunction is closely associated with the development and progression of CVDs. Patients with diabetes mellitus (DM) especially type 2 DM (T2DM) exhibit a significant endothelial cell (EC) dysfunction with substantially increased risk for CVDs. Recent Advances: Excessive reactive oxygen species (ROS) and oxidative stress are important contributing factors to EC dysfunction and subsequent CVDs. ROS production is significantly increased in DM and is critically involved in the development of endothelial dysfunction in diabetic patients. In this review, efforts are made to discuss the role of excessive ROS and oxidative stress in the pathogenesis of endothelial dysfunction and the mechanisms for excessive ROS production and oxidative stress in T2DM. Critical Issues: Although studies with diabetic animal models have shown that targeting ROS with traditional antioxidant vitamins C and E or other antioxidant supplements provides promising beneficial effects on endothelial function, the cardiovascular outcomes of clinical studies with these antioxidant supplements have been inconsistent in diabetic patients. Future Directions: Preclinical and limited clinical data suggest that N-acetylcysteine (NAC) treatment may improve endothelial function in diabetic patients. However, well-designed clinical studies are needed to determine if NAC supplementation would effectively preserve endothelial function and improve the clinical outcomes of diabetic patients with reduced cardiovascular morbidity and mortality. With better understanding on the mechanisms of ROS generation and ROS-mediated endothelial damages/dysfunction, it is anticipated that new selective ROS-modulating agents and effective personalized strategies will be developed for the management of endothelial dysfunction in DM.

Liver glycogen fragility in the presence of hydrogen-bond breakers

Glycogen, a complex branched glucose polymer, is responsible for sugar storage in blood glucose homeostasis. It comprises small β particles bound together into composite α particles. In diabetic livers, α particles are fragile, breaking apart into smaller particles in dimethyl sulfoxide, DMSO; they are however stable in glycogen from healthy animals. We postulate that the bond between β particles in α particles involves hydrogen bonding. Liver-glycogen fragility in normal and db/db mice (an animal model for diabetes) is compared using various hydrogen-bond breakers (DMSO, guanidine and urea) at different temperatures. The results showed different degrees of α-particle disruption. Disrupted glycogen showed changes in the mid-infra-red spectrum that are related to hydrogen bonds. While glycogen α-particles are only fragile under harsh, non-physiological conditions, these results nevertheless imply that the bonding between β particles in α particles is different in diabetic livers compared to healthy, and is probably associated with hydrogen bonding.

Effect of bariatric surgery on metabolism in diabetes and obesity comorbidity: Insight from recent research

Obesity is a prevalent cause of diabetes mellitus (DM) and is a serious danger to human health. Type 2 DM (T2DM) mostly occurs along with obesity. Foodborne obesity-induced DM is caused by an excessive long-term diet and surplus energy. Bariatric surgery can improve the symptoms of T2DM in some obese patients. But different types of bariatric surgery may have different effects. There are some models built by researchers to discuss the surgical procedures’ effects on metabolism in diabetes animal models and diabetes patients. It is high time to conclude all this effects and recommend procedures that can better improve metabolism.

Messagenin–based Chalcones: Synthesis, Modification and Perspectives of Antidiabetic Potency

AbstractA series of messagenin–based chalcones has been synthesized by Claisen‐Schmidt condensation and screened for in vitro α‐glucosidase inhibitory activity. The heterocyclization of 30‐(3‐pyridinylidene)‐messagenin led to syn/anti N‐acetyl‐pyrazoles in a ratio of 2 : 1 that were isolated by HPLC. Messagenin chalcones act as α‐glucosidase inhibitors with IC50 range from 0.055 to 80.70 μM. The lead nanomolar level α‐glucosidase inhibitor 30‐(4‐hydroxymethyl‐benzylidene)‐messagenin 10 was studied for antihyperglycemic activity on streptozotocin–induced diabetic animal models using in vivo mechanism–based assays. In a rat model of STZ‐induced T1DM, compound 10 (20 mg/kg, orally) exhibited antihyperlipidemic activity, reducing AIP (p&gt;0.05) and CRI (p&lt;0.05) compared to control. Compound 10 improved diabetic nephropathy, locomotor activity in rats, and reduced diabetes–related mortality.

Comparative Screening of the Liver Gene Expression Profiles from Type 1 and Type 2 Diabetes Rat Models.

Experimental animal models of diabetes can be useful for identifying novel targets related to disease, for understanding its physiopathology, and for evaluating emerging antidiabetic treatments. This study aimed to characterize two rat diabetes models: HFD + STZ, a high-fat diet (60% fat) combined with streptozotocin administration (STZ, 35 mg/kg BW), and a model with a single STZ dose (65 mg/kg BW) in comparison with healthy rats. HFD + STZ- induced animals demonstrated a stable hyperglycemia range (350-450 mg/dL), whereas in the STZ-induced rats, we found glucose concentration values with a greater dispersion, ranging from 270 to 510 mg/dL. Moreover, in the HFD + STZ group, the AUC value of the insulin tolerance test (ITT) was found to be remarkably augmented by 6.2-fold higher than in healthy animals (33,687.0 ± 1705.7 mg/dL/min vs. 5469.0 ± 267.6, respectively), indicating insulin resistance (IR). In contrast, a more moderate AUC value was observed in the STZ group (19,059.0 ± 3037.4 mg/dL/min) resulting in a value 2.5-fold higher than the average exhibited by the control group. After microarray experiments on liver tissue from all animals, we analyzed genes exhibiting a fold change value in gene expression <-2 or >2 (p-value <0.05). We found 27,686 differentially expressed genes (DEG), identified the top 10 DEGs and detected 849 coding genes that exhibited opposite expression patterns between both diabetes models (491 upregulated genes in the STZ model and 358 upregulated genes in HFD + STZ animals). Finally, we performed an enrichment analysis of the 849 selected genes. Whereas in the STZ model we found cellular pathways related to lipid biosynthesis and metabolism, in the HFD + STZ model we identified pathways related to immunometabolism. Some phenotypic differences observed in the models could be explained by transcriptomic results; however, further studies are needed to corroborate these findings. Our data confirm that the STZ and the HFD + STZ models are reliable experimental models for human T1D and T2D, respectively. These results also provide insight into alterations in the expression of specific liver genes and could be utilized in future studies focusing on diabetes complications associated with impaired liver function.

Bioelectronic modulation of carotid sinus nerve to treat type 2 diabetes: current knowledge and future perspectives.

Bioelectronic medicine are an emerging class of treatments aiming to modulate body nervous activity to correct pathological conditions and restore health. Recently, it was shown that the high frequency electrical neuromodulation of the carotid sinus nerve (CSN), a small branch of the glossopharyngeal nerve that connects the carotid body (CB) to the brain, restores metabolic function in type 2 diabetes (T2D) animal models highlighting its potential as a new therapeutic modality to treat metabolic diseases in humans. In this manuscript, we review the current knowledge supporting the use of neuromodulation of the CSN to treat T2D and discuss the future perspectives for its clinical application. Firstly, we review in a concise manner the role of CB chemoreceptors and of CSN in the pathogenesis of metabolic diseases. Secondly, we describe the findings supporting the potential therapeutic use of the neuromodulation of CSN to treat T2D, as well as the feasibility and reversibility of this approach. A third section is devoted to point up the advances in the neural decoding of CSN activity, in particular in metabolic disease states, that will allow the development of closed-loop approaches to deliver personalized and adjustable treatments with minimal side effects. And finally, we discuss the findings supporting the assessment of CB activity in metabolic disease patients to screen the individuals that will benefit therapeutically from this bioelectronic approach in the future.

A higher butyrate-generation capacity of water-extractable substrates from wheat bran as evidenced by in vitro and in vivo fermentation

Gut microbiota is influenced by the dietary composition and plays important roles in the pathogenesis of metabolic disorders. Thus, wheat bran extract was prepared by either water extraction or enzymatic pre-treatment extraction (referred as AEWB and EHWB, respectively), and then their corresponding impact on short-chain fatty acids generation and gut microbiota was investigated via both in vitro fermentation model and in vivo diabetic animal model. The results of in vitro model indicated that EHWB enhanced the abundance of Megamonas and Faecalibacterium, as well as the amino acids metabolism, which was consistent with the increased butyrate and amino acids metabolites (e.g. iso-butyrate and valerate). The diabetic model analysis suggested that the rats also had an increased amino acid metabolism due to the decreased pathways of amino acid biosynthesis and increased pathways of amino acid degradation following the EHWB intervention. Importantly, the current study revealed that the EHWB intervention led to a greater level of butyrate in the diabetic animal model compared to other groups, demonstrating its prebiotic function, which was supported by the positive correlation between butyrate level and abundance of Bifidobacterium and Lactobacillus. The above results indicated that the main components in water-extractable substrates played key roles in improving the gut microbiota profile and the key metabolite in terms of butyrate. This study might highlight a new ingredient for food industry with physiological functionality.

Propolis of Tubuna bee (Scaptotrigona bipunctata) from the Meliponini tribe alleviates glycaemic, oxidative, and inflammatory conditions during STZ induced diabetes in Wistar rats also aiding in injury recovery

This study was designed to characterize and describe the in vivo effects of an ethanolic propolis extract (EHAP) from the native Brazilian bee Tubuna (Scaptotrigona bipunctata). Propolis has been recently proposed as an adjuvant during diabetes, mainly because propolis possesses various natural compounds without the elevated sugar quantities found in pure honey. Compounds with biological activity and in vitro antioxidant potential have been detected in propolis from Tubuna. Streptozotocin (STZ) is a well-documented model to induce experimental diabetes in rodents. We have detected potential compounds in Tubuna propolis and observed the effects of daily oral treatment with EHAP in Wistar rats during experimental diabetes. EHAP improved glucose tolerance in STZ animals without significantly changing net and organ weight. STZ increases levels of TBARS and Carbonyl, and reduces levels of -SH, effects partially controlled by EHAP, particularly in serum. EHAP decreases inflammatory mediators TnF-ɑ and IL-1β in diabetic animals and decreases paw swelling during carrageenan induced edema. In conclusion, Tubuna propolis constituents possess interesting biological activities to aid in several diseases, but this still needs further studies in these particular pathologies. This is the first work to characterize Tubuna propolis from Rio Grande do Sul and the first work to describe its effects in an animal model of experimental diabetes or any animal model of disease. Treatment with EHAP shows potential to regulate conditions during STZ induced diabetes, aiding in injury recovery paw edema. Mechanistic studies, other models of long-term diabetes or metabolic syndrome, and a complete characterization of propolis from Tubuna are potential targets for future studies.

Investigation of the Cognitive Activity Between the Leaf Extracts of Eclipta alba and Ziziphus jujuba in Diabetic Animal Models.

Diabetes mellitus (DM), a prevalent metabolic disorder, is associated with widespread damage to bodily systems, notably causing significant dysfunction within the peripheral and central nervous systems (CNS). The primary objective of this study is to explore the extent of DM's impact on cognitive and behavioral functions and to evaluate the therapeutic potential of ethanol leaf extracts from Ziziphus jujuba (ZJ) and Eclipta alba (EA) in mitigating these adverse effects. Utilizing an established animal model, we aimed to determine the effectiveness of these plant extracts in ameliorating the cognitive impairments commonly seen in diabetic states. In our experimental framework, we allocated Wistar rats (n=6 per group) into eight different groups, inducing DM through alloxan administration. The intervention groups were treated orally with either the standard antidiabetic drug glibenclamide or varying doses of ZJ and EA extracts over periods of seven and 21 days. Throughout the study, we carefully tracked fluctuations in blood glucose levels, noting considerable decreases, particularly following the 21-day treatment interval. Post-treatment, the rats' cognitive functions were assessed using the Morris water maze (MWM) test. This evaluation revealed significant cognitive enhancement in the diabetic rats administered with ZJ and EA extracts, with these groups displaying reduced latency in finding the submerged platform, indicative of improved learning and memory. These observations were statistically significant (p<0.01). The findings underscore the hypoglycemic effects of ZJ and EA extracts and suggest their viability as cognitive enhancers in the context of DM. The protective effects of these extracts against cognitive decline caused by DM are clear. They add important new information to the research on natural phytochemicals for managing chronic diseases. This study opens new avenues for the application of these substances in treating neurocognitive disorders associated with DM.

Assessment of anti-hyperglycemic and anti-hyperlipidemic effects of thiazolidine-2,4-dione derivatives in HFD-STZ diabetic animal model

Type 2 diabetes mellitus (T2DM) is a chronic endocrine/metabolic disorder characterized by elevated postprandial and fasting glycemic levels that result in disturbances in primary metabolism. In this study, we evaluated the metabolic effects of thiazolidine-2,4-dione derivatives in Wistar rats and Swiss mice that were fed a high-fat diet (HFD) for 4 weeks and received 90 mg/kg of streptozotocin (STZ) intraperitoneally as a T2DM model. The HFD consisted of 17% carbohydrate, 58% fat, and 25% protein, as a percentage of total kcal. The thiazolidine-2,4-dione derivatives treatments reduced fasting blood glucose (FBG) levels by an average of 23.98%–50.84%, which were also improved during the oral starch tolerance test (OSTT). Treatment with thiazolidine-2,4-dione derivatives also improved triglyceride (TG), low-density lipoprotein cholesterol (LDL-c), and total cholesterol levels (P < 0.05). The treatment intake has also shown a significant effect to modulate the altered hepatic and renal biomarkers. Further treatment with thiazolidine-2,4-dione derivatives for 28 days significantly ameliorated changes in appearance and metabolic risk factors, including favorable changes in histopathology of the liver, kidney, and pancreas compared with the HFD/STZ-treated group, suggesting its potential role in the management of diabetes. Thiazolidine-2,4-dione derivatives are a class of drugs that act as insulin sensitizers by activating peroxisome proliferator-activated receptor-gamma (PPAR-γ), a nuclear receptor that regulates glucose and lipid metabolism. The results of this study suggest that thiazolidine-2,4-dione derivatives may be a promising treatment option for T2DM by improving glycemic control, lipid metabolism, and renal and hepatic function.