Diabetic Rat Model Research Articles

Effect of polydeoxyribonucleotide and polynucleotide on rotator cuff healing and fatty infiltration in a diabetic rat model

Failure rate after chronic rotator cuff repair is considerably high. Moreover, diabetes mellitus is known as a compromising factor of rotator cuff tear. The effect of Polydeoxyribonucleotide (PDRN) and polynucleotide (PN) on tendon healing and fatty infiltration is unclear as tissue regeneration activator in diabetic state. Therefore, a diabetic rat model with chronic rotator cuff tear was made for mechanical, histologic and blood tests. In the animal study using a diabetic rat cuff repair model, the administration of PDRN and PN increased the load to failure of repaired cuffs and improved tendon healing and decreased fatty infiltration. Also, the plasma levels of vascular endothelial growth factor and fibroblast growth factor were elevated in PDRN and PN administrated groups. We concluded that PDRN and PN appear to boost tendon recovery and reduce the presence of fatty infiltration following cuff repair in diabetic state. Also, PN showed a later onset and a longer duration than PDRN associated with the mean plasma growth factors.

Bioinspired Collagen Scaffold Loaded with bFGF-Overexpressing Human Mesenchymal Stromal Cells Accelerating Diabetic Skin Wound Healing via HIF-1 Signal Pathway Regulated Neovascularization.

The healing of severe chronic skin wounds in chronic diabetic patients is still a huge clinical challenge due to complex regeneration processes and control signals. Therefore, a single approach is difficult in obtaining satisfactory therapeutic efficacy for severe diabetic skin wounds. In this study, we adopted a composite strategy for diabetic skin wound healing. First, we fabricated a collagen-based biomimetic skin scaffold. The human basic fibroblast growth factor (bFGF) gene was electrically transduced into human umbilical cord mesenchymal stromal cells (UC-MSCs), and the stable bFGF-overexpressing UC-MSCs (bFGF-MSCs) clones were screened out. Then, an inspired collagen scaffold loaded with bFGF-MSCs was applied to treat full-thickness skin incision wounds in a streptozotocin-induced diabetic rat model. The mechanism of skin damage repair in diabetes mellitus was investigated using RNA-Seq and Western blot assays. The bioinspired collagen scaffold demonstrated good biocompatibility for skin-regeneration-associated cells such as human fibroblast (HFs) and endothelial cells (ECs). The bioinspired collagen scaffold loaded with bFGF-MSCs accelerated the diabetic full-thickness incision wound healing including cell proliferation enhancement, collagen deposition, and re-epithelialization, compared with other treatments. We also showed that the inspired skin scaffold could enhance the in vitro tube formation of ECs and the early angiogenesis process of the wound tissue in vivo. Further findings revealed enhanced angiogenic potential in ECs stimulated by bFGF-MSCs, evidenced by increased AKT phosphorylation and elevated HIF-1α and HIF-1β levels, indicating the activation of HIF-1 pathways in diabetic wound healing. Based on the superior biocompatibility and bioactivity, the novel bioinspired skin healing materials composed of the collagen scaffold and bFGF-MSCs will be promising for healing diabetic skin wounds and even other refractory tissue regenerations. The bioinspired collagen scaffold loaded with bFGF-MSCs could accelerate diabetic wound healing via neovascularization by activating HIF-1 pathways.

The effects of Cannabis sativa and cannabinoids on the inhibition of pancreatic lipase – An enzyme involved in obesity

IntroductionObesity is a chronic noncommunicable disease characterized by excessive body fat that can have negative health consequences. Obesity is a complex disease caused by a combination of genetic, environmental, and lifestyle factors. It is characterized by a discrepancy between caloric intake and expenditure. Obesity increases the risk of acquiring major chronic diseases, including heart disease, stroke, cancer, and Type 2 diabetes mellitus (T2DM). Currently, the inhibition of pancreatic lipases (PL) is a promising pharmacological therapy for obesity and weight management. In this study, the inhibition of pancreatic lipase by Cannabis sativa (C. sativa) plant extract and cannabinoids was investigated. MethodsThe inhibitory effect was assessed using p-nitrophenyl butyrate (pNPB), and the results were obtained by calculating the percentage relative activity and assessed using one-way analysis of variance (ANOVA). Kinetic studies and spectroscopy techniques were used to evaluate the mode of inhibition. Diet-induced; and diabetic rat models were studied to evaluate the direct effects of C. sativa extract on PL activity. ResultsKinetic analyses showed that the plant extracts inhibited pancreatic lipase, with tetrahydrocannabinol (THC) and cannabinol (CBN) being the potential cause of the inhibition noted for the C. sativa plant extract. CBN and THC inhibited the pancreatic lipase activity in a competitive manner, with the lowest residual enzyme activity of 52 % observed at a 10 μg/mL concentration of CBN and 39 % inhibition at a 25 μg/mL concentration of THC. Circular dichroism (CD) spectroscopy revealed that the inhibitors caused a change in the enzyme's secondary structure. At low concentrations, THC showed potential for synergistic inhibition with orlistat. C.sativa treatment in an in vivo rat model confirmed its inhibitory effects on pancreatic lipase activity. ConclusionThe findings in this study provided insight into the use of cannabinoids as pancreatic lipase inhibitors and the possibility of using these compounds to develop new pharmacological treatments for obesity.

The neuroprotective role of celastrol on hippocampus in diabetic rats by inflammation restraint, insulin signaling adjustment, Aβ reduction and synaptic plasticity alternation

Celastrol, the primary constituent of Tripterygium wilfordii, has demonstrated neuroprotective properties in rats with dementia by reducing inflammation. A high-fat diet and streptozotocin injection were utilized to establish a diabetic rat model, which was then employed to investigate the possible protective effect of celastrol against the development of diabetes-induced learning and memory deficits. Afterwards, the experimental animals received a dose of celastrol by gavage (4 mg/kg/d). An animal study showed that celastrol enhanced insulin sensitivity and glucose tolerance in diabetic rats. In the Morris water maze test, rats with diabetes performed poorly in terms of spatial learning and memory; treatment with celastrol improved these outcomes. Additionally, administration of celastrol downregulated the expression of inflammatory-related proteins (NF-κB, IKKα, TNF-α, IL-1β, and IL-6) and greatly reduced the generation of Aβ in the diabetic hippocampus tissue. Moreover, the insulin signaling pathway-related proteins PI3K, AKT, and GSK-3β were significantly upregulated in diabetic rats after celastrol was administered. Also, celastrol prevented damage to the brain structures and increased the synthesis of synaptic proteins like PSD-95 and SYT1. In conclusion, celastrol exerts a neuroprotective effect by modulating the insulin signaling system and reducing inflammatory responses, which helps to ameliorate the cognitive impairment associated with diabetes.

Transcriptomic analysis reveals the mechanism of isorhamnetin in the treatment of diabetes mellitus erectile dysfunction

PurposeExploring the therapeutic effect and mechanism of isorhamnetin in the treatment of DMED. MethodsUsing a high glucose environment to induce endothelial cells damage in the corpus cavernosum, and combining with intervention agents such as ferroptosis inhibitors to observe the process of cell damage and repair, evaluating cell status through CCK-8 and DAPI; To establish the STZ-induced diabetes rat model and detect the erectile function and tissue changes; Perform transcriptomic sequencing on rat models and samples treated with isorhamnetin to analyze differentially expressed genes and their GO functions; Identify critical pathways by combining with the ferroptosis database; Flow cytometry was used to detect ROS and mitochondrial membrane potential, and RT-PCR was used to verify gene expression, Seahorse detects mitochondrial oxygen consumption rate, revealing the mechanism of action of isorhamnetin. ResultsFerroptosis inhibitors and isorhamnetin can effectively reverse the damage of corpus cavernosum endothelial cells induced by high glucose and ferroptosis agonists. Isorhamnetin has the ability to reinstate the erectile function of diabetic rats, while enhancing the quantity of endothelial cells and refining the morphology of collagen fibers. Immunohistochemistry revealed that ferroptosis existed in the penis tissue of diabetes rats. Transcriptomic analysis showed that isorhamnetin improves gene expression in DM rats by regulating genes such as GFER, IGHM, GPX4 and HMOX1, involving multiple pathways and biological processes. Flow cytometry and RT-PCR confirmed that isorhamnetin can reduce reactive oxygen species levels, restore essential gene expression, improve mitochondrial membrane potential, and alleviate oxidative stress and ferroptosis. Seahorse detection found that isorhamnetin can restore mitochondrial oxygen consumption rate. ConclusionIsorhamnetin attenuates high glucose damage to cavernous endothelial cells by inhibiting ferroptosis and oxidative stress, restores erectile function and improves tissue morphology in diabetic rats, and its multi-pathway and multi-targeting regulatory mechanism suggests that it is promising to be an effective drug for the treatment of DMED.

Abstract 43: PAR1 Inhibition with Vorapaxar Enhances Renal Function and Modulates Inflammation Mediators in Diabetic Nephropathy

Diabetic nephropathy (DN) is the leading cause of end-stage renal failure, and hypertension is a comorbidity in about 90% of all cases. Characteristics of pathological changes of DN include severe albuminuria, renal hyperfiltration, glomerular basement membrane thickening, and glomerulosclerosis. Identifying the molecular mechanisms underlying DN is critical for developing more effective therapeutic approaches. Thus, interventions targeting podocytes have become a major focus for diseases like DN due to their crucial role in regulating glomerular permeability and maintaining glomerular structures. Our previous studies have demonstrated that serine proteases and Protease-activated receptor 1 (PAR1) are involved in developing DN through TRPC6-mediated calcium signaling in podocytes. Utilizing a PAR1 heterozygous knockout rat model with a type 2 diabetic background, we showed that reducing PAR1 expression decreases microalbuminuria and glomerular damage. This study aims to define the effects and potential mechanisms of pharmacological blockade of PAR1 on the development of DN. To achieve this, 16-week-old T2DN rats were treated with a potent and selective PAR1 antagonist (vorapaxar (SCH 530348), 10 mg/kg of diet) for 16 weeks to determine the effect of PAR1 inhibition. We found improvements in glomerular filtration rate (GFR) in treated animals compared to control after 16 weeks of treatment (0.8 ± 0.2 vs 1.2 ± 0.2 mL/min/100g b.w., p=0.029, N≥4). We observed a trend toward differences in basal intracellular calcium concentration in podocytes between the control and treated groups, although these changes were not statistically significant (202 ± 95 vs 152 ± 75 nM, p=0.19, n≥10, N=3). Additionally, inhibition of PAR1 caused modulation in the inflammation-resolution mediators in the kidney with significant upregulation of Maresins Conjugates in Tissue Regeneration (MCTR1) and downregulation of hydroxy-docosahexaenoic acids (7-,14-,17-HDHA). Changes in GFR may be linked to reduced glomerular damage, indicating that the structural integrity of the glomeruli is better maintained in treated animals. Alterations in the lipidomic profile could indicate a reduction in the inflammatory processes typically associated with DN. Overall, our data indicates that vorapaxar improves glomerular filtration rate and modulates lipid mediators in a type 2 diabetic rat model. This suggests that targeting PAR1 could be a promising therapeutic strategy for diabetic nephropathy.

Curcumin-loaded gold nanoparticles with enhanced antibacterial efficacy and wound healing properties in diabetic rats

Diabetic wounds pose a significant global health challenge. Although curcumin exhibits promising wound healing and antibacterial properties, its clinical potential is limited by low aqueous solubility, and poor tissue penetration. This study aimed to address these challenges and enhance the wound healing efficacy of curcumin by loading it onto gold nanoparticles (AuNPs). The properties of the AuNPs, including particle size, polydispersity index (PDI), zeta potential, percent drug entrapment efficiency (%EE) and UV–Vis spectra were significantly influenced by the curcumin/gold chloride molar ratio used in the synthesis of AuNPs. The optimal formulation (F2) exhibited the smallest particle size (41.77 ± 6.8 nm), reasonable PDI (0.59 ± 0.17), high %EE (94.43 ± 0.25 %), a moderate zeta potential (−8.44 ± 1.69 mV), and a well-defined surface Plasmon resonance peak at 526 nm. Formulation F2 was incorporated into Pluronic® F127 gel to facilitate its application to the skin. Both curcumin AuNPs solution and gel showed sustained drug release and higher skin permeation parameters compared with the free drug solution. AuNPs significantly enhanced curcumin’s antibacterial efficacy by lowering the minimum inhibitory concentrations and enhancing antibacterial biofilm activity against various Gram-positive and Gram-negative bacterial strains. In a diabetic wound rat model, AuNPs-loaded curcumin exhibited superior wound healing attributes compared to the free drug. Specifically, it demonstrated improved wound healing percentage, reduced wound oxidative stress, increased wound collagen deposition, heightened anti-inflammatory effects, and enhanced angiogenesis. These findings underscore the potential of AuNPs as efficacious delivery systems of curcumin for improved wound healing applications.

Abstract P104: Kidney arteriolar responses to liver-targeted small interference RNA (siRNA) targeting angiotensinogen in diabetic rats: comparison with other renin-angiotensin system blockers

Objective: Inhibition of the renin-angiotensin system (RAS) with ACE inhibitors (ACEi) or angiotensin receptor blockers (ARB) is associated with concentric thickening of renal arteries and arterioles and parenchymal disease. Here we evaluated to what degree this also occurs during RAS inhibition with siRNA targeting hepatic angiotensinogen (AGT). Methods: Male hypertensive heterozygous transgenic rats overexpressing mouse renin (TGR(mRen2)27 rats), made diabetic with streptozotocin, were treated with the ARB valsartan (4 mg/kg/day), the ACEi captopril (6 mg/kg/day), AGT siRNA (30 mg/kg every 2 weeks), AGT siRNA + valsartan, or captopril + valsartan for 3 weeks, starting at 15 weeks after induction of diabetes. After 3 weeks of treatment, kidneys were removed, and immunocytochemistry was performed on Bouin’s fixed kidney sections using antibodies against renin or α-smooth muscle actin. Juxtaglomerular index and wall thickness were assessed using tiling pictures of both renin and α-smooth muscle actin sections from the slides. Tubular degeneration was scored by summing up scores for tubular atrophy, interstitial fibrosis, and tubulointerstitial inflammation. Concentric vascular hypertrophy was assessed in a blinded manner. Results: All treatments increased juxtaglomerular index, and the largest increases were observed in dual treatment groups, consistent with the highest degree of RAS blockade in these groups. Tubular scores increased after induction of diabetes, and the highest scores were seen in dual treatment groups, significance versus vehicle being reached in the valsartan + captopril group only (P<0.05). Afferent arteriole wall thickness increased in all treatment groups, and the greatest increases were observed during dual treatment. Finally, concentric vascular hypertrophy was observed in 1 of 7 (14%) diabetic Ren2 rats; this percentage increased during RAS blocker treatment of these rats, numerically reaching the highest values during dual treatment. Conclusions: Our data suggest that, in the hypertensive diabetic rat model, high levels of RAS blockade, irrespective of the type of blockade, may result in an increase in afferent arteriole thickness and concentric vascular hypertrophy. AGT siRNA in combination with RAS inhibitors should be further explored in clinical studies.

O52 KIDNEY ARTERIOLAR RESPONSES TO LIVER-TARGETED SMALL INTERFERENCE RNA (SIRNA) TARGETING ANGIOTENSINOGEN IN DIABETIC RATS: COMPARISON WITH OTHER RENIN-ANGIOTENSIN SYSTEM BLOCKERS

Objective: Inhibition of the renin-angiotensin system (RAS) with ACE inhibitors (ACEi) or angiotensin receptor blockers (ARB) is associated with concentric thickening of renal arteries and arterioles and parenchymal disease. Here we evaluated to what degree this also occurs during RAS inhibition with siRNA targeting hepatic angiotensinogen (AGT). Methods: Male hypertensive heterozygous transgenic rats overexpressing mouse renin (TGR(mRen2)27 rats), made diabetic with streptozotocin, were treated with the ARB valsartan (4 mg/kg/day), the ACEi captopril (6 mg/kg/day), AGT siRNA (30 mg/kg every 2 weeks), AGT siRNA + valsartan, or captopril+valsartan for 3 weeks, starting at 15 weeks after induction of diabetes. After 3 weeks of treatment, kidneys were removed, and immunocytochemistry was performed on Bouin's fixed kidney sections using antibodies against renin or α-smooth muscle actin. Juxtaglomerular index and wall thickness were assessed using tiling pictures of both renin and α-smooth muscle actin sections from the slides. Tubular degeneration was scored by summing up scores for tubular atrophy, interstitial fibrosis, and tubulointerstitial inflammation. Concentric vascular hypertrophy was assessed in a blinded manner. Results: All treatments increased juxtaglomerular index, and the largest increases were observed in dual treatment groups, consistent with the highest degree of RAS blockade in these groups. Tubular scores increased after induction of diabetes, and the highest scores were seen in dual treatment groups, significance versus vehicle being reached in the valsartan+captopril group only (P<0.05). Afferent arteriole wall thickness increased in all treatment groups, and the greatest increases were observed during dual treatment. Finally, concentric vascular hypertrophy was observed in 1 of 7 diabetic Ren2 rats; this percentage increased during RAS blocker treatment of these rats, numerically reaching the highest values during dual treatment. Conclusions: Our data suggest that, in the hypertensive diabetic rat model, high levels of RAS blockade, irrespective of the type of blockade, may result in an increase in afferent arteriole thickness and concentric vascular hypertrophy. AGT siRNA in combination with RAS inhibitors should be further explored in clinical studies.

Effects of Catechin Intake on Oxidative Stress and Kidney Tissue in Obese Type 2 Diabetic Model Rats

Effects of Catechin Intake on Oxidative Stress and Kidney Tissue in Obese Type 2 Diabetic Model Rats

Comparison of St. John's wort oil and thiocilline ointment on wound healing in a diabetic rat model

Aims: In diabetic patients, wound healing is impaired and wounds are often infected with multifactorial agents. This study aimed to compare the effectiveness of St. John’s wort and ointment containing bacitracin-neomycin (thiocilline) to improve wound healing in a diabetic infected wound model. Methods: Rats in which diabetes was induced by administering 60 mg/kg streptozotocin (STZ) were considered diabetic if their blood sugar levels were above 300 mg/dl 72 hours later. Group 1: Control (Non diabetic) group, Group 2: Diabetes group. During wound care, both groups were disinfected with povidone iodine (PI) and the right lumbar region of each rat was dressed with thiocilline and the left lumbar region was dressed with St. John’s wort oil. Considering the wound healing period, the study was terminated after an average of 20 days. In histopathological examination, ulceration, necrosis, epithelialization, congestion, edema, polymorphous nucleated leukocyte (PNL), monocyte, fibroblast, and neovascularization were evaluated. Results: In histopathological evaluation, there was a statistically significant decrease in ulceration and necrosis in the group treated with St. John’s wort oil compared to the group given thiocilline (p=0.04). In terms of epithelialization, there was a statistically significant increase in the group dressed with St. John’s wort oil compared to the group given thiocilline (p=0.03). There was a statistically significant decrease in congestion and edema in the group treated with St. John’s wort oil compared to the group given thiocilline (p=0.03). There was a statistically significant increase in fibroblast and neovascularization in the group treated with St. John’s wort oil compared to the group given thiocilline (p=0.02). Conclusion: Histopathologic ally, epithelialization, fibroblast, and neovascularization, which have important functions in the wound healing process, increased in diabetic rats administered St. John’s wort. Although it is used in traditional medicine due to its antidepressant effectiveness, we believe that St. John’s wort can be used in wounds that develop in diabetic patients, as it has the potential to increase the wound healing process.

EFFECTIVENESS OF WEST SUMATRAN DADIAH ON REDUCING HYPERGLYCAEMIA AND LIPID PROFILE IN DIABETIC RATS

The high incidence of DM (Diabetes Mellitus) has made diabetes a global health problem that is often associated with other health problems and high treatment costs. For this reason, complementary therapies such as Dadiah are needed. Dadiah is fermented buffalo milk from West Sumatra. This study aims to determine the effectiveness of Dadiah on reducing hyperglycaemia and lipid profile of diabetic model rats. The experimental study used 25 rats divided into five groups. Group 1 was negative control, group 2 was positive control, group 3 was DM rats with Dadiah intervention at a dose of 3g/300gBB, group 4 was DM with metformin 13.5mg/kgBB, and group 5 was DM with a combination of Dadiah and Metformin. After STZ induction, each group was given the intervention for six weeks, and the blood sugar and cholesterol levels were observed. The average decrease in blood sugar levels and cholesterol levels close to the negative control group was obtained in the Dadiah and metformin combination treatment group (P3) with an average blood sugar level of 124.2 mg/dL, total cholesterol level of 78.4 mg/dL, HDL level of 28.2 mg/dL, LDL level of 27.8 mg/dL and triglycerides 113.6 mg/dL. The administration of Dadiah and the combination of Dadiah with Metformin proved to have the highest effectiveness in alleviating hyperglycaemia and hypercholesterolemia in diabetes mellitus model rats.

Improvement of Liver Function (AST and ALT) and Liver Tissue Catalase levels of Wistar rats induced with Alloxan by consuming Catfish oil extract

Background: Background: Type 2 Diabetes Mellitus (T2DM) is characterized by disrupted glucose metabolism, leading to hyperglycemia and insulin resistance, often associated with Secondary Hypertension (SH). Over 80% of SH patients exhibit glucose intolerance, with nearly 30% developing T2DM. There is a strong interaction between T2DM and NAFLD, representing a complex two-way relationship that influences the prognosis of the two diseases. Catfish oil extract boasts unsaturated fatty acids, including DHA, EPA, omega-3, vitamins A, B6, B12, D, and amino acids. Objective: This study aims to assess the impact of Pangasius sp. (catfish) oil extract administration on serum AST and ALT levels, as well as liver tissue MDA and CAT levels in alloxan-induced Wistar rats (Rattus norvegicus). Materials and Methods: Employing a pure experimental approach with a post-test-only control group design, three groups of 9 white male rats (Rattus norvegicus), along with one extra male rat, were included.K1 served as the negative control group (Wistar rats not subjected to any treatment). K2 acted as the positive control group (Wistar rats subjected to alloxan-induced diabetes at 150mg/kg BW). K3 represented the treatment group (diabetic model rats treated with catfish oil extract at 73mg/kg BW). Serum AST and ALT levels, as well as MDA and CAT levels in liver tissue, were measured at the study's conclusion. Results: The highest mean MDA levels in white rat liver tissue were K2 (3034.00 + 525.25 nmol/g), and the lowest was K3(2909.33+351.01nmol/g); the mean CAT liver tissue levels in rats the highest was K1 (1063.42+133.36U/mg), and the lowest was K3(894.78+132.93U/mg), the highest mean serum ALT levels of white rats was K2(230.34+63,58 U/L), and the lowest was K1(151.54+23.12 U/L) and the highest mean serum AST level in rats was K2(448.79+618.90U/L), and the lowest was K1(61.01+14.70U/L). Conclusion: Giving catfish oil supplementation can repair the damage in liver tissue, as evidenced by reductions in MDA levels and serum ALT and AST levels in diabetic model rats within the treatment group. Alloxan induction did not affect liver tissue CAT levels, as evidenced by a consistent decrease in liver tissue CAT levels in both the positive control and treatment groups.

Antidiabetic effects of aqueous leaf extract of Vernonia amygdalina on serum liver markers in streptozotocin-induced diabetic albino Rats: a new data to support its Anti-diabetic effect

BackgroundNumerous plants have been explored for their potential antidiabetic properties, and Vernonia amygdalina (VA) stands among them. This study aims to investigate the antidiabetic activities of VA and validate its efficacy.MethodsAn aqueous extract of Vernonia amygdalina leaves was obtained through maceration. The antidiabetic effects of this plant extract were evaluated in vivo using diabetic model rats. Albino Wistar rats were induced into a diabetic state through intraperitoneal injection of streptozocin and subsequently treated with an optimal dose of 250 mg/kg aqueous extract of VA over a 21-day period. Parameters such as body weight, blood glucose levels, and serum marker enzymes were measured.ResultsThe results demonstrated a significant reduction (p < 0.05) in the glucose levels of streptozocin-induced diabetic rats following treatment with VA extract, highlighting its potential as an antidiabetic agent that performed comparably to the reference drug, glimepiride. Additionally, a significant increase (p < 0.05) in the body weight of the treated diabetic rats was observed. Aqueous extracts also significantly (p < 0.05) altered the serum concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in a manner similar to the glimepiride-treated group.ConclusionThis study affirms the anti-diabetic effects of the aqueous extract of Vernonia amygdalina in streptozotocin-induced diabetic rats and suggests that the extract holds promise as an important phytomedicine for the development of more effective treatments for diabetes.

Chlorogenic acid ameliorates memory dysfunction via attenuating frontal lobe oxidative stress and apoptosis in diabetic rat model.

Diabetes mellitus, characterized by hyperglycemia, causes various complications, one of which is memory dysfunction. The frontal lobe is known to be responsible for impaired memory function due to hyperglycemia and is associated with oxidative stress-mediated neuronal cell apoptosis. Chlorogenic acid (CGA) is reported to have neuroprotective effects. However, its effect on the frontal lobe in diabetes mellitus (DM) rats is not widely known. This research aimed to elucidate the effect of CGA on the mRNA expressions of SOD1, SOD2, p53, and Bcl-2 in the frontal lobe of DM rats. Thirty male Wistar rats (2-month-old, 150-200 gBW) were randomly divided into six groups: C (control), DM1.5 (1.5-month DM), DM2 (2-month DM), CGA12.5, CGA25 and CGA50 (DM+CGA 12.5, 25, and 50 mg/kgBW, respectively). A single dose of streptozotocin (60 mg/kgBW) was intraperitoneally injected. Intraperitoneal CGA injection was administered daily for DM1.5 rats for 14 days. Path length was measured in the Morris water maze (MWM) probe test. After termination, the frontal lobes were carefully harvested for RNA extraction. Reverse transcriptase PCR was performed to examine the mRNA expression of SOD1, SOD2, p53, and Bcl-2. The DM2 group demonstrated significant shorter path length on the MWM probe test and significantly lower mRNA expression of SOD1 and Bcl-2, compared to the C group. After CGA administration, the CGA25 group showed a significantly shorter path length than the C group. The CGA12.5 and CGA25 groups had significantly higher mRNA expression of SOD1 than the DM1.5 group. Compared to the DM1.5 and DM2 groups, SOD2 mRNA expression of the administration of all three CGA doses increased markedly. Furthermore, Bcl-2 mRNA expression was significantly increased in the CGA12.5 and CGA50 groups, compared with the DM2 group. Chlorogenic acid might improve memory function through upregulation of frontal lobes' SOD1, SOD2, and Bcl-2 mRNA expression in DM rats.

Evaluating the Healing Properties of Quercetin-Enhanced Nanoparticle Ointments in Diabetic Rats

Background: Wound healing problems pose a significant clinical challenge for individuals with diabetes, necessitating innovative treatment strategies. Phenyl Boronic Acid-Quercetin (PBA-Q) nanoparticles offer potential benefits due to their antioxidant, anti-inflammatory, and wound-healing properties. Objective: This study aimed to investigate the morphological events associated with wound healing in diabetic rat models treated with PBA-Q nanoparticles ointment. Methods: Male Albino Wistar rats with streptozotocin-induced diabetes were used. Diabetes was confirmed with blood glucose levels exceeding 250 mg/dL. Excisional wounds of 2 cm diameter were created on the dorsum of each rat. The PBA-Q nanoparticles ointment was applied topically on days 3, 7, 11, and 15 post-wounding. Wound contraction was measured using a Vernier caliper, and tissues were collected for histopathological analysis, immunohistochemistry, and electron microscopy. Statistical analysis was performed using SPSS version 25.0. Results: Compared to controls, diabetic rats treated with PBA-Q nanoparticles showed significantly accelerated wound closure by 42% on day 15, enhanced re-epithelialization, increased collagen deposition by 50%, and reduced inflammatory cell infiltration by 60%. Vascularization was notably improved, with a 70% increase in blood vessel formation by day 15. Conclusion: PBA-Q nanoparticles ointment significantly enhanced wound healing in diabetic rats, demonstrating therapeutic potential for diabetic wound management. Further research is needed to validate these findings in human clinical trials.

Effects of Mung Bean Water Supplementation on Modulating Lipid and Glucose Metabolism in a Diabetic Rat Model.

Type 2 diabetes mellitus (T2DM) is often associated with chronic inflammation exacerbated by hyperglycemia and dyslipidemia. Mung beans have a longstanding reputation in traditional medicine for their purported ability to lower blood glucose levels, prompting interest in their pharmacological properties. This study aimed to explore the impact of mung bean water (MBW) on carbohydrate and lipid metabolism in a T2DM rat model induced by nicotinamide/streptozotocin. Normal and DM rats were supplemented with a stock solution of MBW as drinking water ad libitum daily for 8 weeks. MBW supplementation led to significant reductions in plasma total cholesterol, HDL-C, and VLDL-C + LDL-C levels, and decreased malondialdehyde levels in plasma and liver samples, indicating reduced oxidative stress. MBW supplementation lowered plasma glucose levels and upregulated hepatic hexokinase activity, suggesting enhanced glucose utilization. Additionally, MBW decreased hepatic glucose-6-phosphate dehydrogenase and glutathione peroxidase activities, while hepatic levels of glutathione and glutathione disulfide remained unchanged. These findings underscore the potential of MBW to improve plasma glucose and lipid metabolism in DM rats, likely mediated by antioxidant effects and the modulation of hepatic enzyme activities. Further exploration of bioactive components of MBW and its mechanisms could unveil new therapeutic avenues for managing diabetes and its metabolic complications.

The Bioactive Interface of Titanium Implant with Both Anti-Oxidative Stress and Immunomodulatory Properties for Enhancing Osseointegration under Diabetic Condition.

The poor implant-osseointegration under diabetic condition remains a challenge to be addressed urgently. Studies have confirmed that the diabetic pathological microenvironment is accompanied by excessive oxidative stress, imbalanced immune homeostasis, and persistent chronic inflammation, which seriously impairs the osteogenic process. Herein, a multifunctional bioactive interface with both anti-oxidative stress and immunomodulatory properties is constructed on titanium implants. Briefly, manganese dioxide nanosheets are coated onto mesoporous polydopamine nanoparticles loaded with carbon monoxide gas precursor, namely MnO2-CO@MPDA NPs, and then they are integrated on the titanium implant to obtain MCM-Ti. In the simulated diabetic microenvironment, under the action of MnO2 nanoenzymes, MCM-Ti can effectively eliminate intracellular reactive oxygen species while alleviating hypoxic state. Interestingly, the microenvironment mediates the responsive release of CO gas, which effectively drives macrophages toward M2 polarization, thereby ameliorating inflammatory response. The potential mechanism is that CO gas up-regulates the expression of heme oxygenase-1, further activating the Notch/Hes1/Stat3 signaling pathway. Furthermore, the conditioned medium derived from macrophages on MCM-Ti surface significantly enhances the osteogenic differentiation of BMSCs. In a type 2 diabetic rat model, MCM-Ti implant effectively alleviates the accompanying inflammation and enhances the osseointegration through the synergistic effects of resisting oxidative stress and remodeling immune homeostasis.

Multifunctional Nanosystem for Dual Anti-Inflammatory and Antibacterial Photodynamic Therapy in Infectious Diabetic Wounds.

Infectious diabetic wounds present a substantial challenge, characterized by inflammation, infection, and delayed wound healing, leading to elevated morbidity and mortality rates. In this work, we developed a multifunctional lipid nanoemulsion containing quercetin, chlorine e6, and rosemary oil (QCRLNEs) for dual anti-inflammatory and antibacterial photodynamic therapy (APDT) for treating infectious diabetic wounds. The QCRLNEs exhibited spherical morphology with a size of 51 nm with enhanced encapsulation efficiency, skin permeation, and localized delivery at the infected wound site. QCRLNEs with NIR irradiation have shown excellent wound closure and antimicrobial properties in vitro, mitigating the nonselective cytotoxic behavior of PDT. Also, excellent biocompatibility and anti-inflammatory and wound healing responses were observed in zebrafish models. The infected wound healing properties in S. aureus-infected diabetic rat models indicated re-epithelization and collagen deposition with no signs of inflammation. This multifaceted approach using QCRLNEs with NIR irradiation holds great promise for effectively combating oxidative stress and bacterial infections commonly associated with infected diabetic wounds, facilitating enhanced wound healing and improved clinical outcomes.

Artemisia vulgaris Extract as a Novel Therapeutic Approach for Reversing Diabetic Cardiomyopathy in a Rat Model.

Diabetic cardiomyopathy, a severe diabetic complication, impairs heart function, leading to heart failure. Treatment that effectively addresses this condition without causing side effects is urgently needed. Current anti-hyperglycemic therapies are expensive, has side effects and do not effectively prevent cardiac remodeling. Therefore, it is important to explore natural products that may have the potential to reverse cardiac remodeling. That is why the aim of the current study was to determine the left ventricular remodeling potential of the methanolic extract of Artemisia vulgaris in a diabetic cardiomyopathy rat model. Following the initial comprehensive phytochemical evaluation of plant phenolic and flavonoid content, which showed strong anti-hyperglycemic and antioxidant activities, an extract of Artemisia vulgaris was administered in an in vivo experiment. Diabetic cardiomyopathy was induced in Wistar albino rats according to previously described protocols in the literature, and the effect of treatment was checked by serum and histopathological analysis after 45 days. Artemisia vulgaris treatment significantly (p ≤ 0.05) reduced fasting blood glucose (108.5 ± 1.75 mg/dL), glycated hemoglobin (4.03 ± 0.12 %), serum glucose (116.66 ± 3.28 mg/dL), insulin (15.66 ± 0.66 ng/mL), total oxidant status (54.66 ± 3.22 µmol H2O2Equiv.L-1), Malondialdehyde (0.20 ± 0.01 mmol/L), total cholesterol (91.16 ± 3.35 mg/dL), triglycerides (130.66 ± 3.15 mg/dL), low-density lipids (36.57 ± 1.02 mg/dL), sodium (140 ± 3.21 mmol/L), calcium (10.44 ± 0.24 mmol/L), creatine kinase MB (1227.5 ± 17.89 IU/L), lactate dehydrogenase (1300 ± 34.64 IU/L), C-reactive protein (30 ± 0.57 pg/mL), tumor necrosis factor-α (58.66 ± 1.76 pg/mL), atrial natriuretic peptide (2.53 ± 0.04 pg/mL), B-type natriuretic peptide (10.66 ± 0.44 pg/mL), aspartate aminotransferase (86.5 ± 4.99 U/L), Alanine Transaminase (55.33 ± 2.90 U/L), urea (25.33 ± 1.15 mg/dL) and creatinine (0.64 ± 0.02 mg/dL) but significantly increased (p ≤ 0.05) total antioxidant capacity (1.73 ± 0.07 mmol Trolox Equil./L), high-density lipids (40 ± 1.59 mg/dL) and potassium (3.82 ± 0.04 mmol/L) levels. ECG and histopathology confirmed the significant improvement in remodeling and the reversal of structural changes in the heart and pancreas. In conclusion, Artemisia vulgaris possesses significant left ventricular remodeling potential in course of diabetes-induced cardiomyopathy.