Diabetic Rat Model Research Articles

Tibial cortex transverse transport promotes ischemic diabetic foot ulcer healing via enhanced angiogenesis and inflammation modulation in a novel rat model

BackgroundTibial Cortex Transverse Transport (TTT) represents an innovative surgical method for treating lower extremity diabetic foot ulcers (DFUs), yet its underlying mechanisms remain elusive. Establishing an animal model that closely mirrors clinical scenarios is both critical and novel for elucidating the mechanisms of TTT.MethodsWe established a diabetic rat model with induced hindlimb ischemia to mimic the clinical manifestation of DFUs. TTT was applied using an external fixator for regulated bone movement. Treatment efficacy was evaluated through wound healing assessments, histological analyses, and immunohistochemical techniques to elucidate biological processes.ResultsThe TTT group demonstrated expedited wound healing, improved skin tissue regeneration, and diminished inflammation relative to controls. Marked neovascularization and upregulation of angiogenic factors were observed, with the HIF-1α/SDF-1/CXCR4 pathway and an increase in EPCs being pivotal in these processes. A transition toward anti-inflammatory M2 macrophages indicated TTT's immunomodulatory capacity.ConclusionOur innovative rat model effectively demonstrates the therapeutic potential of TTT in treating DFUs. We identified TTT's roles in promoting angiogenesis and modulating the immune system. This paves the way for further in-depth research and potential clinical applications to improve DFU management strategies.

Influence of Lemongrass Essential Oil (Cymbopogon flexuosus) Supplementation on Diabetes in Rat Model.

(1) Background: Species of the genus Cymbopogon and its essential oil are known for their antioxidant and hypoglycemic effects. This study aimed to investigate the impact of the essential oil of Cymbopogon flexuosus (EOCF), and its major component, citral, on glycemic, lipid, antioxidant parameters, and oxidative stress in a type 1 diabetes (DM1) rat model. (2) Methods: Initially, EOCF was analyzed by Gas chromatography-mass spectrometry (GC-MS) and the antioxidant activity of EOCF and citral was evaluated. Next, male Wistar rats (3 months old, 200-250 g) induced with DM1 using Streptozotocin (STZ) were divided into four groups: negative control supplemented with an 80% Tween solution, two groups of animals supplemented with EOCF (32 mg/kg and 64 mg/kg) and with citral (32 mg/kg), and treated for 14 days. Measurements of blood glucose levels and body weight were taken; after euthanasia, biochemical markers, including lipid profile, uric acid, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), were evaluated. (3) Results: The predominant compounds in EOCF were α-citral (53.21%) and neral (19.42%), constituting 72.63% citral. EOCF showed good antioxidant activity, significantly greater than citral. EOCF supplementation demonstrated a mitigating effect on glycemic, lipid, and hepatic abnormalities induced by DM1. (4) Conclusions: EOCF emerges as a promising therapeutic option for the management of DM1.

The impact of vitamin D on type 2 diabetes management: boosting PTP1B gene expression and physical activity benefits in rats

BackgroundThe protein tyrosine phosphatase 1B (PTP1B) plays a crucial role in the development of insulin resistance. Aerobic training (AT) and vitamin D (Vit D) supplementation have been shown to individually improve glucose tolerance and diabetes-related factors. However, the impact of their combined effect on PTP1B gene expression and serum irisin in the visceral adipose tissue remains unknown. This study aims to investigate whether 8 weeks of combined AT with Vit D supplementation can improve the expression of PTP1B in adipose tissue and serum irisin in obese rats with type 2 diabetes (T2D).MethodsFifty male Wistar rats were divided into two groups: diabetic (n = 40) and non-diabetic (ND; n = 10). The diabetic rats were further divided into four groups: aerobic training with vitamin D supplementation (D + AT + Vit D; n = 10), aerobic training only (D + AT; n = 10), vitamin D supplementation only (D + Vit D; n = 10), and control (D + C; n = 10). The D + Vit D and D + AT + Vit D groups received 5000 IU of vitamin D via injection once a week, while the D + AT and D + C groups received sesame oil. Diabetes was induced in all groups except the nondiabetic group by intraperitoneal (IP) injection of streptozotocin. At the end of the intervention, blood and adipose tissue samples were collected, and RNA was extracted from adipose tissue for real-time PCR analysis of PPTP1B gene expression.ResultsThere was an increase in serum Vit D and irisin levels and a decrease in HOMA-IR and PTP1B gene expression in the diabetic rat model treated with D + AT and injected with 50,000 IU/kg/week of Vit D. Comparatively, when treated with D + AT + Vit D, the downregulation of PTP1B was significantly higher (p = 0.049; p = 0.004), and there was a significant increase in irisin (p = 0.010; p = 0.001).ConclusionThe present study shows that the combined AT and Vit D supplementation positively impacts the expression of PTP1B in adipose tissue and serum irisin in rats with T2D. These findings suggest that combining AT with Vit D supplementation can provide a new and effective strategy to improve glucose tolerance and diabetes-related factors in individuals with T2D by regulating the expression of PTP1B in adipose tissue and promoting the synthesis of beneficial irisin protein.

Comparison of in vivo pharmacokinetics of twelve constituents in Qihe Fenqing Yin in normal rats and diabetic rats

This paper aims to study the pharmacokinetic differences of twelve effective constituents(succinic acid, neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, protocatechuic aldehyde, caffeic acid, 5-O-ferulogeninic acid, p-coumaric acid, nuciferine, quercetin, oleanolic acid, and ursolic acid) in Qihe Fenqing Yin in normal and diabetic rats. The diabetic rat model was established by a high-fat diet combined with intraperitoneal injection of streptozocin. A UHPLC-QTRAP-MS/MS method was established for the simultaneous determination of 12 constituents in the plasma of normal rats and model rats after a single intragastric administration of Qihe Fenqing Yin. The results show that the established analytical method has a good linear relationship with the 12 components, and the specificity, accuracy, precision, and stability meet the requirements. The computational pharmacokinetic parameters are fitted by DAS 3.2.8 software, and the results show that the half-life time(t_(1/2)) of the other nine components in the model group was longer than that in the normal group except for caffeic acid, 5-O-ferulogeninic acid, and oleanolic acid. The area under curve(AUC_(0-t)) of cryptochlorogenic acid, p-coumaric acid, ursolic acid, and oleanolic acid increases compared with the normal group. Meanwhile, mean residence time(MRT) delays. The "double peaks" of quercetin and nuciferine in the normal group are not observed in the model group, suggesting that the pharmacokinetic parameters of the drugs in the disease state are significantly different.

Mentha piperita silver nanoparticle-loaded hydrocolloid film for enhanced diabetic wound healing in rats.

To investigate the role of Mentha piperita silver nanoparticle-loaded carbopol gel for enhanced wound healing in a diabetic rat model. This research further aims to explore bioactive compounds derived from Mentha piperita obtained from high altitude. Methanolic extracts of Mentha piperita (MP), Mentha spicata (MS) and Mentha longifolia (ML) were used to synthesise silver nanoparticles (AgNP). AgNP synthesis was confirmed by ultraviolet-visible (UV-Vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The antioxidant activity was assessed by 2, 2-diphenyl-1-picrylhydrazyl (DDPH) assay. Antiglycation potential was determined by measuring the fluorescent advanced glycation end products. The bioactive compound identified in the Mentha piperita methanolic (MPM) fraction through electrospray ionisation tandem mass spectrometric analysis (ESI-MS) was responsible for the highest antiglycation. The effects of MPM and MPM.AgNP-loaded Carbopol (Sanare Lab, India) on wound healing were compared in male, alloxan-induced, diabetic albino rats (200-250g), divided into control and treated groups. Effects on wound healing were assessed via histopathology. UV-Vis and FTIR confirmed NP synthesis with peaks for flavonoids and polyphenols. SEM and XRD explored the cubical, 30-63nm crystalline NP. The maximum antioxidant and antiglycation potential was observed in order of; MP.AgNP>MS.AgNP>ML.AgNP. The highest antioxidant activity was observed by methanolic and aqueous MP.AgNPs (88.55% and 83.63%, respectively) at 2mg.ml-1, and (75.16% and 69.73%, respectively) at 1mg.ml-1, compared to ascorbic acid (acting as a positive control, 90.01%). MPM.AgNPs demonstrated the best antiglycation potential of 75.2% and 83.3% at 1mg.ml-1 and 2mg.ml-1, respectively, comparable to positive control (rutin: 88.1%) at 14 days post-incubation. A similar trend was observed for antimicrobial activity against Bacillus subtilis, Micrococcus luteus and Escherichia coli with an inhibition zone of 21mm, 21.6mm and 24.6mm. Rosmarinic acid was the active compound present in Mentha piperita, as identified by ESI-MS. MPM.AgNP-loaded Carbopol resulted in 100% wound closure compared with control at 20 days post-wounding. In the treatment group, re-epithelialisation was achieved by day 18, compared with 25 days for the positive control group. MPM.AgNP-loaded Carbopol demonstrated safer and more effective biological properties, hence accelerating the diabetic excision wound healing process in alloxan-induced diabetic rats.

IDF23-0393 Effect of Zingiber officinale ethanolic extract on insulin receptor gene in nSTZ-induced diabetic model rats

IDF23-0393 Effect of Zingiber officinale ethanolic extract on insulin receptor gene in nSTZ-induced diabetic model rats

Lactobacillus Plantarum Promotes Wound Healing by Inhibiting the NLRP3 Inflammasome and Pyroptosis Activation in Diabetic Foot Wounds.

Diabetic foot ulcer (DFU) impairs the quality of life of diabetic patients and overburdens healthcare systems and society. It is crucial to comprehend the pathophysiology of DFU and develop effective treatment strategies. The aim of this study was to to evaluate the therapeutic potential of Lactobacillus Plantarum (LP) on wound healing in DFU and to explore the underlying mechanisms. To investigate the effects of LP on wound healing, human umbilical vein endothelial cells (HUVECs) were treated with advanced glycation end products (AGEs) and used to assess cell viability, migration, and pyroptosis using CCK-8, cell scratch, and flow cytometry. The levels of IL-1β and IL-18 were measured by ELISA. The expression of NLRP3, caspase-1 p20, and GSDMD-N was detected by Western blot. Additionally, NLRP3 inhibitor MCC950 was used to treat a diabetic rat model established by streptozotocin (STZ). Pearson correlation analysis was performed to analyze the relationship between LP and NLRP3, IL-1β, IL-18 in ulcer tissue. Our data mechanistically demonstrate that AGEs activate the NLRP3/Caspase-1/GSDMD pathway, leading to an increase in the levels of IL-1β and IL-18 and ultimately promoting cell pyroptosis. Furthermore, we identified that LP inhibits the effects of AGEs by downregulating NLRP3 inflammasome activity. LP facilitated wound healing in diabetic rats and resulted in decreased protein levels of NLRP3 and its downstream target caspase-1 p20. Finally, we observed a negative correlation between LP and NLRP3, IL-1β, IL-18 in diabetic foot skin tissue. Our findings uncovered a novel role of LP in diabetic foot wound healing via regulation of the NLRP3 inflammasome, suggesting this link as a therapeutic target. In future research, it would be valuable to explore the signaling cascades involved in LP-mediated inhibition of NLRP3 inflammasome activation.

Comparative effects of pravastatin and rosuvastatin on carbohydrate metabolism in an experimental diabetic rat model.

Statin treatment may increase the risk of diabetes; there is insufficient data on how statins affect glucose regulation and glycemic control and the effects of statins on liver enzymes related to carbohydrate metabolism have not been fully studied. Therefore, we aimed to compare the effects of the statin derivatives, pravastatin, and rosuvastatin, on carbohydrate metabolism in an experimental diabetic rat model. Female Wistar albino rats were used and diabetes was induced by intraperitoneal injection of streptozotocin. Thereafter, 10 and 20 mg kg-1 day-1 doses of both pravastatin and rosuvastatin were administered by oral gavage to the diabetic rats for 8 weeks. At the end of the experiment, body masses, the levels of fasting blood glucose, serum insulin, insulin resistance (HOMA-IR), liver glycogen, and liver enzymes related to carbohydrate metabolism were measured. Both doses of pravastatin significantly in creased the body mass in diabetic rats, however, rosuvastatin, especially at the dose of 20 mg kg-1 day-1 reduced the body mass signi ficantly. Pravastatin, especially at a dose of 20 mg kg-1 day-1, caused significant increases in liver glycogen synthase and glucose 6-phosphate dehydrogenase levels but significant decreases in the levels of glycogen phosphorylase, lactate dehydrogenase, and glucose-6-phosphatase. Hence, pravastatin partially ameliorated the adverse changes in liver enzymes caused by diabetes and, especially at the dose of 20 mg kg-1 day-1, reduced the fasting blood glucose level and increased the liver glycogen content. However, rosuvastatin, especially at the dose of 20 mg kg-1 day-1, significantly reduced the liver glycogen synthase and pyruvate kinase levels, but increased the glycogen phosphorylase level in diabetic rats. Rosuvastatin, 20 mg kg-1 day-1 dose, caused significant decreases in the body mass and the liver glycogen content of diabetic rats. It can be concluded that pravastatin, especially at the dose of 20 mg kg-1 day-1 is more effective in ameliorating the negative effects of diabetes by modulating carbohydrate metabolism.

Synergistic Interaction between Topical Application of Allicin and Quercetin Enhances Diabetic Wound Healing Via Inflammatory in Wistar Rats

Prolonged and excessive inflammatory processes at the wound site result in delayed healing of diabetic wounds. Allicin and quercetin have significantly inhibited tumor necrosis factor alpha (TNF-α) and increased levels of transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF) in rats. However, there is no known investigation on the combination of both compounds on TNF-α, TGF-β, and VEGF as a topical healing agent via inflammatory mechanisms. This study aims to determine the synergistic interaction between topical application of allicin and quercetin in enhancing diabetic wound healing via inflammatory in Wistar rats. A total of 45 male Wistar rats weighing 180-250 g were induced diabetes by a single intraperitoneal injection of streptozotocin (45 mg/kg bw). Diabetic rats underwent wound creation under anaesthesia and a square-shaped open excision wound was made with a full-thickness measurement of 1 cm × 1 cm on the right side of the rat's back. Rats were randomly allocated into group namely, vehicle control, allicin, quercetin, and a combination of allicin and quercetin which is applied topically once a day at a dose of 10 mg/mL for 7 days. Our finding showed that once daily topical application of allicin and quercetin, both independently and synergistically, increased levels of TGF-β and VEGF, as well as decreased levels of TNF-α of the rat diabetic wound model compared with the vehicle control group over 7th day. The synergistic effects of allicin and quercetin significantly enhanced diabetic wound healing via inflammation in rats, by suppressing inflammatory cytokines and stimulating growth factors hence offering a new window of an experimental study.

Protective Effect of Black Rice Cyanidin-3-Glucoside on Testicular Damage in STZ-Induced Type 1 Diabetic Rats.

Diabetic testicular damage is quite a common and significant complication in diabetic men, which could result in infertility. The natural fertility rate of type 1 diabetes men is only 50% because of testicular damage. This research first aimed to explore the intervention effect of C3G on testicular tissue damage induced by diabetes. Here, a streptozotocin-induced type 1 diabetic rat model was established, and then C3G was administered. After 8 weeks of C3G supplementation, the symptoms of diabetes (e.g., high blood glucose, lower body weight, polydipsia, polyphagia) were relieved, and at the same time that sperm motility and viability increased, sperm abnormality decreased in C3G-treated diabetic rats. Furthermore, the pathological structure of testis was restored; the fibrosis of the testicular interstitial tissue was inhibited; and the LH, FSH, and testosterone levels were all increased in the C3G-treated groups. Testicular oxidative stress was relieved; serum and testicular inflammatory cytokines levels were significantly decreased in C3G-treated groups; levels of Bax, Caspase-3, TGF-β1 and Smad2/3 protein in testis decreased; and the level of Bcl-2 was up-regulated in the C3G-treated groups. A possible mechanism might be that C3G improved antioxidant capacity, relieved oxidative stress, increased anti-inflammatory cytokine expression, and inhibited the apoptosis of spermatogenic cells and testicular fibrosis, thus promoting the production of testosterone and repair of testicular function. In conclusion, this study is the first to reveal that testicular damage could be mitigated by C3G in type 1 diabetic rats. Our results provide a theoretical basis for the application of C3G in male reproductive injury caused by diabetes.

Skin wound healing in diabetic rat model using low-dose photodynamic therapy.

Chronic wound is one of the major challenges in medicine and imposes a heavy financial burden on the healthcare of different countries. Diabetic foot ulcers as one of the important examples for chronic wounds can lead to lower limb amputation, disability, and death in diabetics. In this regard, novel technology with low side effects got attention in recent years. Low-dose photodynamic therapy (LDPDT) is one of the noninvasive techniques that can be considered for wound healing in diabetic wounds. In this experiment, we aim to study the effect of LDPDT on diabetic rats' wound healing and compare it to healthy rats. In this in vitro experimental study, 32 male rats were used. Rats in both normal and diabetic (streptozotocin injection) groups after being wounded (two wounds [0.8×0.8cm]) on the back of each rat were randomly divided into four groups, including the control group (without treatment), radiation-only (660nm-1 J/cm2 ) group, 5-ALA-only (1µg/mL) group, and LDPDT-recipient group. The procedure has been done for 2days, and at the end of Days 3, 7, 14, and 21, the wound sample was sent to the histopathology laboratory, and the wound size and tissue indices in these groups were evaluated by histology and microscopy techniques. The impact of low concentrations of 5-ALA and low irradiation energy density in both normal and diabetic rats were positive, which accelerated the wound-healing process as seen in the histology study. In diabetic rats treated with only radiation and LDPDT, the process of epithelial regeneration, collagen production, reduction of mast cells, and production of follicles was more as compared to the normal group. The results suggest that LDPDT can have a positive impact on the diabetic rat model wound healing.

Translational application of human keratinocyte-fibroblast cell sheets for accelerated wound healing in a clinically relevant type 2 diabetic rat model

Despite advancements in wound care, wound healing remains a challenge, especially in individuals with type 2 diabetes. Cell sheet technology has emerged as an efficient and promising therapy for tissue regeneration and wound repair. Among these, bilayered human keratinocyte-fibroblast cell sheets constructed using temperature-responsive culture surfaces have been shown to mimic a normal tissue-like structure and secrete essential cytokines and growth factors that regulate the wound healing process. Therefore, this study aimed to evaluate the safety and therapeutic potential of human skin cell sheets to treat full-thickness skin defects in a rat model of type 2 diabetes. Our findings demonstrate that diabetic wounds transplanted with bilayered cell sheets resulted in accelerated re-epithelialization, increased angiogenesis, enhanced macrophage polarization and regeneration of tissue that closely resembled healthy skin. In contrast, the control group that did not receive cell sheet transplantation presented characteristic symptoms of impaired and delayed wound healing associated with type 2 diabetes. The secretory cytokines and the upregulation of Nrf2 expression in response to cell sheet transplantation are believed to have played a key role in the improved wound healing observed in diabetic rats. Our study suggests that human keratinocyte-fibroblast cell sheets hold great potential as a therapeutic alternative for diabetic ulcers.

Study on effects and relevant mechanisms of Mudan granules on renal fibrosis in streptozotocin-induced diabetes rats

Aims The effects and relevant mechanisms of Mudan granules in the renal fibrosis of diabetic rats were explored through in vivo experiments, which provided a scientific basis for expanding their clinical indications. Methods Male SD rats were given a single intraperitoneal injection of STZ (65 mg/kg) to induce diabetes rat models. After treatment with Mudan granules, the general condition of rats was recorded. Blood glucose, blood lipids, and renal function-related indicators were detected, renal tissue morphological changes and fibrosis-related indicators were observed, and the expression of pathway-related proteins were examined. Results The general condition of diabetes rats was improved after the treatment of Mudan granules, the 24-h urinary protein and urinary albumin to creatinine ratio were reduced, and the renal function and lipid results were modified. The tissue damage to the rat kidney has been repaired. Expression of TGF-β1/Smad-related pathway proteins was suppressed in kidney tissues, and the fibrosis factor CO-IV, FN, and LN were reduced in serum. Conclusion Mudan granules may inhibit of TGF-β1/Smad pathway, inhibit the production of ECM, reduce the levels of fibrosis factors CO-IV, FN, and LN, to have a protective effect on kidney in diabetes rats.

Blow-Spun Si3N4-Incorporated Nanofibrous Dressing with Antibacterial, Anti-Inflammatory, and Angiogenic Activities for Chronic Wound Treatment

The effective and safe healing of chronic wounds, such as diabetic ulcers, presents a significant clinical challenge due to the adverse microenvironment in the wound that hinders essential processes of wound healing, including angiogenesis, inflammation resolution, and bacterial control. Therefore, there is an urgent demand for the development of safe and cost-effective multifunctional therapeutic dressings. Silicon nitride, with its distinctive antibacterial properties and bioactivities, shows great potential as a promising candidate for the treatment of chronic wounds. In this study, a silicon nitride-incorporated collagen/chitosan nanofibrous dressing (CCS) were successfully fabricated using the solution blow spinning technique (SBS). SBS offers compelling advantages in fabricating uniform nanofibers, resulting in a three-dimensional fluffy nanofibrous scaffold that creates an optimal wound healing environment. This blow-spun nanofibrous dressing exhibits excellent hygroscopicity and breathability, enabling effective absorption of wound exudate. Importantly, the incorporated silicon nitride within the fibers triggers surface chemical reactions in the aqueous environment, leading to the release of bioactive ions that modulate the wound microenvironment. Here, the CCS demonstrated exceptional capabilities in absorbing wound exudate, facilitating water vapor transmission, and displaying remarkable antibacterial properties in vitro and in a rat infected wound model (up to 99.7%, 4.5 × 107 CFU/cm2 for Staphylococcus aureus). Furthermore, the CCS exhibited an enhanced wound closure rate, angiogenesis, and anti-inflammatory effects in a rat diabetic wound model, compared to the control group without silicon nitride incorporation.Graphical abstract

Beneficial Effects of Natural Alkaloids from Berberis glaucocarpa as Antidiabetic Agents: An In Vitro, In Silico, and In Vivo Approach.

Diabetes, also known as diabetes mellitus (DM), is a metabolic disorder characterized by an abnormal rise in blood sugar (glucose) levels brought on by a complete or partial lack of insulin secretion along with corresponding changes in the metabolism of lipids, proteins, and carbohydrates. It has been reported that medicinal plants play a pivotal role in the treatment of various ailments such as diabetes mellitus, dyslipidemia, and hypertension. The current study involved exploring the acute toxicity and in vivo antidiabetic activity of berberine (WA1), palmatine (WA2), and 8-trichloromethyl dihydroberberine (WA3) previously isolated from Berberis glaucocarpa Stapf using a streptozotocin (STZ)-induced diabetic rat model. Body weight and blood glucose level were assessed on a day interval for 4 weeks. Biochemical parameters, antioxidant enzymes, and oxidative stress markers were also determined. In an acute toxicity profile, the WA1, WA2, and WA3 were determined to be nontoxic up to 500 mg/kg (b.w). After the second and third weeks of treatment (14 and 21 days), the blood glucose levels in the WA1-, WA2-, and WA3-treated groups were significantly lower than those in the diabetic control group (476.81 ± 8.65 mg/dL, n = 8, P < 0.001). On the 21st day, there was a decrease in the blood glucose level and the results obtained were 176.33 ± 4.69, 197.21 ± 4.80, and 161.99 ± 4.75 mg/dL (n = 8, P < 0.001) for WA1, WA2, and WA3 at 12 mg/kg, respectively, as opposed to the diabetic control group (482.87 ± 7.11 mg/dL, n = 8, P < 0.001). Upon comparison with the diabetic group at the end of the study (28 days), a substantial drop in the glucose level of WA3 at 12 mg/kg (110.56 ± 4.11 mg/dL, n = 8, P < 0.001) was observed that was almost near the values of the normal control group. The treated groups (WA1, WA2, and WA3) treated with the samples displayed a significant decline in the levels of HbA1c. Treatment of the samples dramatically lowered the lipid level profile. In groups treated with samples, plasma levels of triglycerides, total cholesterol, and LDL were significantly lowered [F (5, 42) = 100.6, n = 8, P < 0.001]; these levels were also significantly decreased [F (5, 42) = 129.6 and 91.17, n = 8, P < 0.001]. In contrast to the diabetes group, all treated groups had significantly higher HDL levels [F (5, 42) = 15.46, n = 8, P < 0.001]. As a result, hypolipidemic activity was anticipated in the samples. In addition to that, the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was considerably elevated in the groups treated with the sample compared to the diabetic control group (n = 8, P < 0.001).

Silibinin as a promising treatment for diabetes: Insights into behavioral and metabolic changes in an animal model.

Diabetes mellitus is causing serious health problems in the chronic period. Silibinin is a flavonoid obtained from the milk thistle (Silybum marianum), which is among the herbal ethnopharmacological administrations. In studies with silibinin, it has been reported that it increases the activity of pancreatic beta cells and insulin sensitivity and has a hyperglycemia-reducing effect. However, behavioral parameters have not been evaluated together with insulin levels and liver function tests. Our aim in this study was to examine the effects of silibinin on insulin secretion, anxiety-like behaviors, and learning in a streptozotocin (STZ)-induced rat diabetes model. Wistar albino rats weighing 200-250 g were divided into 4 groups. Control: Saline solution, Diabetes: STZ 45 mg/kg, S 100: STZ 45 mg/kg + Silibinin 100 mg/kg, S 200: STZ 45 mg/kg + Silibinin 200 mg/kg. Administrations were continued for 21 days. On the 21st day, open field and elevated plus maze as unconditional anxiety tests; Barnes maze for learning and memory; and rotarod test for locomotor activity were conducted. Following behavioral tests, blood samples were taken under anesthesia. Blood glucose levels and ALT values were measured. Insulin levels were measured with an ELISA plate reader. Silibinin shortened the time to find the correct hole. Silibinin prevented the decrease in insulin due to STZ, exhibited a hyperglycemia-reducing effect and decreased the elevation of ALT.

Anti-Diabetic Potentials ofLactobacillus Strains by Modulating Gut Microbiota Structure and β-Cells Regeneration in the Pancreatic Islets of Alloxan-Induced Diabetic Rats.

Diabetes mellitus, a most common endocrine disorder of glucose metabolism, has become a global epidemic and poses a serious public health threat with an increased socio-economic burden. Escalating incidence of diabetes is correlated with changes in lifestyle and food habits that cause gut microbiome dysbiosis and β-cells damage, which can be addressed with dietary interventions containing probiotics. Hence, the search for probiotics of human origin with anti-diabetic, anti-AGE, and anti-ACE potentials has gained renewed interest for the effective management of diabetes and its associated complications. The present study used an alloxan (AXN)-induced diabetic rat model to investigate the effects of potential probiotic Lacticaseibacillus casei MKU1, Lactiplantibacillus pentosus MKU3, and Lactiplantibacillus plantarum MKU7 administration individually on physiochemical parameters related to diabetic pathogenesis. Experimental animals were randomly allotted into six groups viz. NCG (control), DCG (AXN), DGM (metformin), DGP1 (MKU1), DGP2 (MKU3), and DGP3 (MKU7), and biochemical data like serum glucose, insulin, AngII, ACE, HbA1c, and TNF-α levels were measured until 90days. Our results suggest that oral administration with MKU1, MKU3, or MKU7 significantly improved serum insulin levels, glycemic control, glucose tolerance, and body weight. Additionally, β-cell mass was increased by preserving islet integrity in Lactobacillus-treated diabetic rats, whereas TNF-α (~40%), AngII (~30%), and ACE levels (~50%) were strongly inhibited and enhanced sIgA production (5.8 folds) abundantly. Furthermore, Lactobacillus administration positively influenced the gut microbiome with a significant increase in the abundance of Lactobacillus species and the beneficial Bacteroides uniformis and Bacteroides fragilis, while decreased the pathogenic Proteus vulgaris and Parabacteroides distasonis. Among the probiotic treatment groups, L. pentosus MKU3 performed greatly in almost all parameters, indicating its potential use for alleviating diabetes-associated complications.

Separable Microneedle for Integrated Hyperglycemia Sensing and Photothermal Responsive Metformin Release.

Microdevices that offer hyperglycemia monitoring and controllable drug delivery are urgently needed for daily diabetes management. Herein, a theranostic separable double-layer microneedle (DLMN) patch consisting of a swellable GelMA supporting base layer for glycemia sensing and a phase-change material (PCM) arrowhead layer for hyperglycemia regulation has been fabricated. The Cu-TCPP(Fe)/glucose oxidase composite and 3,3',5,5'-tetramethylbenzidine coembedded in the supporting base layer permit a visible color shift at the base surface in the presence of glucose via a cascade reaction, allowing for the in situ detection of glucose in interstitial fluid. The PCM arrowhead layer is encapsulated with water monodispersity melanin nanoparticles from Sepia officinalis and metformin that is imparted with a near-infrared ray photothermal response feature, which is beneficial to the controllable release of metformin for suppression of hyperglycemia. By applying the DLMN patch to the streptozotocin-induced type 2 diabetic Sprague-Dawley rat model, the results demonstrated that it can effectively extract dermal interstitial fluid, read out glucose levels, and regulate hyperglycemia. This DLMN-integrated portable colorimetric sensor and self-regulated glucose level hold great promise for daily diabetes management.

Management of wounds in diabetes by administering allicin and quercetin in emulsion form as wound medicine in diabetic rat models.

Wounds in diabetes is a complex problem that requires effective treatment at a high cost. Adjuvant therapy from natural bioactive elements can be an alternative to overcome problems in diabetic wound healing disorders. Allicin and quercetin are natural bioactive substances contained in several fruit or vegetable plants that have various pharmacological effects. The purpose of this study was to determine the effect of allicin and quercetin in emulsion form as wound medicine in helping the wound healing process. Diabetic wistar rats with wounds on their backs measuring 1 × 1 cm were divided into four treatment groups which were given wound medicine once a day for seven days according to their distribution. The wound healing process was evaluated on the third and seventh day. Data were observed and analyzed using appropriate statistical tools. Measurement of wound healing indicators was carried out by examining wound contraction and histopathological examination showing that the treatment group given the allicin and quercetin formula experienced an improvement compared to the treatment group without allicin and quercetin. Allicin and quercetin increase the percentage of wound contraction, increase the density of blood vessels and the epithelialization process in the wound so that the wound healing process becomes faster. In conclusion, allicin and quercetin can be effective adjuvant therapies in helping wound healing in diabetes. Wound medication in the form of an emulsion is an effective choice, because it can maintain the stability of the allicin and quercetin content and can make the wound environment moist.

Downregulation of VEGFA accelerates AGEs-mediated nucleus pulposus degeneration through inhibiting protective mitophagy in high glucose environments

Intervertebral disc degeneration (IVDD) contributes largely to low back pain. Recent studies have highlighted the exacerbating role of diabetes mellitus (DM) in IVDD, mainly due to the influence of hyperglycemia (HG) or the accumulation of advanced glycation end products (AGEs). Vascular endothelial growth factor A (VEGFA) newly assumed a distinct impact in nonvascular tissues through mitophagy regulation. However, the combined actions of HG and AGEs on IVDD and the involved role of VEGFA remain unclear. We confirmed the potential relation between VEGFA and DM through bioinformatics and biological specimen detection. Then we observed that AGEs induced nucleus pulposus (NP) cell degeneration by upregulating cellular reactive oxygen species (ROS), and HG further aggravated ROS level through breaking AGEs-induced protective mitophagy. Furthermore, this adverse effect could be strengthened by VEGFA knockdown. Importantly, we identified that the regulation of VEGFA and mitophagy were vital mechanisms in AGEs-HG-induced NP cell degeneration through Parkin/Akt/mTOR and AMPK/mTOR pathway. Additionally, VEGFA overexpression through local injection with lentivirus carrying VEGFA plasmids significantly alleviated NP degeneration and IVDD in STZ-induced diabetes and puncture rat models. In conclusion, the findings first confirmed that VEGFA protects against AGEs-HG-induced IVDD, which may represent a therapeutic strategy for DM-related IVDD.