Activity In Diabetic Rats Research Articles

Effect of Replacing Soybean Flour by Germinated Quinoa Flour on the Physicochemical Characteristics of Vegan Burgers and Biological Activities in Diabetic Rats

Effect of Replacing Soybean Flour by Germinated Quinoa Flour on the Physicochemical Characteristics of Vegan Burgers and Biological Activities in Diabetic Rats

Male Sprague Dawley Rats with Type 2 Diabetes Mellitus and Obesity on Body Weight, Body Mass Index, and Fat Content as Affected by Alkaloid Fraction of Litsea Glutinosa Leaves (AFLG)

There were 463 million people living with diabetes around the world, and it is expected to increase by 48% in 2045. Dipeptidyl Peptidase 4 (DPP4) inhibitor is asecond-line anti-diabetic drug, that frequently causes weight gain for long term treatment. Alkaloid fraction of L. glutinosa leaves (AFLG) is able to inhibit DPP4 activity in diabetic rats. Therefore, this study aimed to evaluate the effect of AFLG on body weight (BW), BMI, and fat percentage in male rats with model type 2 diabetes mellitus (T2DM) and obesity. Male Sprague Dawley rats, which weighed 200-250 g, were used in this experimental study. Twelve rats were fed with a high-fat diet for 30 days and then were intraperitoneally injected with 230 and 65 mg/kg BW nicotinamide and streptozotocin, respectively. Those rats were randomly divided into 4 groups, control (C) and three treatment (T1-T3) groups, which were orally given 20, 40, and 80 mg/kg BW/day AFLG for 28 days. Collected data were analyzed using a paired t-test, the one-way ANOVA test. Significant differences in BW in T2 and T3 (p = 0.001), Rohrer index in T2 (p = 0.001) and fat content in C (p = 0.013) were observed between before and after treatments. The average of BW, Lee, Rohrer, and TM indexes and fat content in treatment groups did not significantly differ from the C group after 28 days of treatment (p > 0.005). In conclusion, Alkaloid fraction of L. glutinosa leaves does not influence body weight, nutrition status, or fat content of male rats’ models of T2DM and obesity.

Investigating the Impact of Hibiscus Extracts on Paraoxonase and Antioxidant Activities in Diabetic Rats

Objective: Diabetes mellitus (DM) accelerates oxidative stress beyond its broad effects on metabolic function, which has been linked to various chronic complications. This study investigated the antioxidative and therapeutic potential of Hibiscus syriacus (HSE) and Hibiscus trionum extracts (HTE), focusing on their effects on paraoxonase (PON) and arylesterase enzymes activity in diabetic rat models. Material and Methods: This study evaluated PON and ARE activities in 36 Wistar albino rats divided into the following groups: control (C), C+HSE, C+HTE, Diabetes (D), D+HSE, and D+HTE. The total phenolic content of HSE and HTE was determined using the Folin- Ciocalteu method, and their antioxidant activities were assessed using DPPH and CUPRAC tests. Results: HSE and HTE extracts have demonstrated significant increases in paraoxonase and arylesterase activities, which are crucial for cardiovascular protection and reducing oxidative stress in diabetes. Conclusions: This study highlights the potential of natural extracts in managing oxidative stress-related complications associated with diabetes and underscores the need to integrate such phytotherapeutic agents into broader diabetes care strategies. Future research should focus on confirming these findings in clinical settings and investigating the molecular processes responsible for the observed effects, potentially paving the way for innovative interventions for diabetes management.

Hepatoprotective potential of taxifolin in type 2 diabetic rats: modulation of oxidative stress and Bcl2/Bax/Caspase-3 signaling pathway.

Diabetes mellitus (DM) is a global metabolic problem. Several factors including hyperglycemia, oxidative stress, and inflammation play significant roles in the development of DM complications. Apoptosis is also an essential event in DM pathophysiology, -with B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) determining apoptotic susceptibility. The present study aimed to elucidate the protective effects of two doses of taxifolin (TXF) on liver damage in diabetic rats and explore the possible mechanisms of action. DM was induced in eighteen rats through intraperitoneal injections of 50mg/kg streptozotocin and 110mg/kg nicotinamide. Diabetic rats received daily oral intubation of 25 and 50mg/kg TXF for 3 months. In the untreated diabetic group, there was a significant increase in fasting and postprandial glucose levels, glycosylated hemoglobin A1C (HbA1c), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), while insulin and adiponectin levels decreased significantly. Both TXF doses mitigated hyperglycemia, regulated cytokine production, and increased insulin level. Gene expressions and protein levels of Bax, caspase 3, and cytochrome c were significantly increased, while Bcl-2 was significantly decreased in the livers of diabetic rats, effects that were significantly ameliorated after TXF treatment. The results of the TUNEL assay supported the apoptotic pathway. Additionally, TXF significantly decreased lipid peroxidation and enhanced antioxidant enzyme activity in diabetic rats. Liver enzymes and histopathological changes also showed improvement. TXF mitigated diabetes-associated hepatic damage by reducing hyperglycemia, oxidative stress, inflammation, and modulating anti-/pro-apoptotic genes and proteins. A dose of 50mg/kg TXF was more effective than 25mg/kg and is recommended for consumption.

Effect of Swimming Exercise on Levels of Blood Glucose, Adiponectin, Glucose-6-Phosphatase and Lipid Profile in Diabetic Wistar Rats

Diabetes mellitus is a chronic metabolic condition that causes persistent hyperglycemia due to insulin action or secretion. Regular physical exercise has been reported to improve glycemia and lipid profile in diabetes. However, literature is scare on the effects of swimming exercise on the serum levels of adiponectin and glucose 6 phosphatase in Wister rats with diabetes This study therefore, investigated the effects of swimming exercise on adiponectin, glucose 6-phosphatase and lipid profile in male Wistar rats with streptozotocin-induced diabetes. This study was carried out on 25 male Wistar rats grouped into five groups (n=5/group): group 1=control, group 2=diabetes, group 3=diabetes treated with metformin, group 4=non-diabetes and swimming exercise, group 5=diabetes and swimming exercise. Animals in groups 2, 3, and 5 were induced with Streptozotocin (STZ) 50 mg/kg intraperitoneally. After 72 hours of diabetes induction, animals with a blood glucose level of ≥ 200 mg/dl were confirmed diabetics and used for the study. Group 3 animals were treated with metformin 200mg/kg giving orally for 28 days. Animals in groups 4 and 5 were subjected to swimming exercises for 5-10 minutes during the first week until they could swim freely for 30 minutes. The animals were then allowed to swim 5 days per week for 28 days. Swimming exercise for 28 days significantly reduced blood glucose, glucose-6-phosphatase (G6Ppase), Lactate dehydrogenase (LDH), Total cholesterol (TC), and Low-density lipoprotein (LDL) levels but caused significant increase in adiponectin and High-density lipoprotein (HDL) levels in diabetic rats compared with untreated diabetic rats. There was a significant decrease in triglyceride (TG) of diabetic animals caused by swimming for 28 days. This study demonstrated that swimming exercise for 28 days may help lower glucose level and improve insulin sensitivity by increasing adiponectin level and decreasing G6Pase activity in diabetic rats. Also, swimming exercise may help improve lipid profile in diabetic rats.

Insights into the Cardioprotective Effects of Pyridoxine Treatment in Diabetic Rats: A Study on Cardiac Oxidative Stress, Cardiometabolic Status, and Cardiovascular Biomarkers.

The aims of this study were to examine the effects of pyridoxine administration on the activities of cardiac antioxidant stress enzymes superoxide dismutase (SOD) and catalase (CAT) and enzyme indicators of cardiometabolic status, lactate and malate dehydrogenase (LDH, MDH), as well as LDH and MDH isoforms' distribution in the cardiac tissue of healthy and diabetic Wistar male rats. Experimental animals were divided into five groups: C1-control (0.9% sodium chloride-NaCl-1 mL/kg, intraperitoneally (i.p.), 1 day); C2-second control (0.9% NaCl 1 mL/kg, i.p., 28 days); DM-diabetes mellitus (streptozotocin 100 mg/kg in 0.9% NaCl, i.p., 1 day); P-pyridoxine (7 mg/kg, i.p., 28 days); and DM + P-diabetes mellitus and pyridoxine (streptozotocin 100 mg/kg, i.p., 1 day and pyridoxine 7 mg/kg, i.p., 28 days). Pyridoxine treatment reduced CAT and MDH activity in diabetic rats. In diabetic rats, the administration of pyridoxine increased LDH1 and decreased LDH4 isoform activities, as well as decreased peroxisomal MDH and increased mitochondrial MDH activities. Our findings highlight the positive effects of pyridoxine administration on the complex interplay between oxidative stress, antioxidant enzymes, and metabolic changes in diabetic cardiomyopathy.

Cannabidiol and Beta-Caryophyllene Combination Attenuates Diabetic Neuropathy by Inhibiting NLRP3 Inflammasome/NFκB through the AMPK/sirT3/Nrf2 Axis.

In this study, we investigated in detail the role of cannabidiol (CBD), beta-caryophyllene (BC), or their combinations in diabetic peripheral neuropathy (DN). The key factors that contribute to DN include mitochondrial dysfunction, inflammation, and oxidative stress. Briefly, streptozotocin (STZ) (55 mg/kg) was injected intraperitoneally to induce DN in Sprague-Dawley rats, and we performed procedures involving Randall Sellito calipers, a Von Frey aesthesiometer, a hot plate, and cold plate methods to determine mechanical and thermal hyperalgesia in vivo. The blood flow to the nerves was assessed using a laser Doppler device. Schwann cells were exposed to high glucose (HG) at a dose of 30 mM to induce hyperglycemia and DCFDA, and JC1 and Mitosox staining were performed to determine mitochondrial membrane potential, reactive oxygen species, and mitochondrial superoxides in vitro. The rats were administered BC (30 mg/kg), CBD (15 mg/kg), or combination via i.p. injections, while Schwann cells were treated with 3.65 µM CBD, 75 µM BC, or combination to assess their role in DN amelioration. Our results revealed that exposure to BC and CBD diminished HG-induced hyperglycemia in Schwann cells, in part by reducing mitochondrial membrane potential, reactive oxygen species, and mitochondrial superoxides. Furthermore, the BC and CBD combination treatment in vivo could prevent the deterioration of the mitochondrial quality control system by promoting autophagy and mitochondrial biogenesis while improving blood flow. CBD and BC treatments also reduced pain hypersensitivity to hyperalgesia and allodynia, with increased antioxidant and anti-inflammatory action in diabetic rats. These in vivo effects were attributed to significant upregulation of AMPK, sirT3, Nrf2, PINK1, PARKIN, LC3B, Beclin1, and TFAM functions, while downregulation of NLRP3 inflammasome, NFκB, COX2, and p62 activity was noted using Western blotting. the present study demonstrated that STZ and HG-induced oxidative and nitrosative stress play a crucial role in the pathogenesis of diabetic neuropathy. We find, for the first time, that a CBD and BC combination ameliorates DN by modulating the mitochondrial quality control system.

Antihyperglycemic, Antihyperlipidemic, and Antioxidant Effects of Morin on Streptozotocin-Induced Diabetic Rats

Recently, natural remedies for the management of diabetes observed a rise in interest as a result of the negative impacts of conventional treatment. The present work studies the beneficial effects of morin in normal and streptozotocin-induced diabetic rats on glucose levels, tissue antioxidant state, and lipid peroxidation. Oral delivery of morin (25 and 50 mg/kg body weight/day) for 21 days to normal and diabetic rats could not prevent weight loss, but consumption of food and water (25 mg/kg) was considerably reduced. Morin substantially decreased glucose, total cholesterol, triglycerides, LDL cholesterol, and VLDL cholesterol in the blood of diabetic rats. Additionally, it greatly halted the rise in aspartate aminotransferase and alanine aminotransferase levels as well as the decline in HDL cholesterol levels in diabetic rats. In comparison to normal rats, diabetic rats had higher levels of malondialdehyde, lower levels of nitric oxide, decreased glutathione, and lower levels of superoxide dismutase in their hepatic, renal, and pancreatic tissues. The morin treatments substantially reduced the levels of hepatic and pancreatic reduced glutathione, hepatic and pancreatic reduced nitric oxide, and hepatic, renal, and pancreatic superoxide dismutase. They also prevented the increase of hepatic, renal, and pancreatic malondialdehyde. Histopathological findings revealed a reduction in pancreatic damage in morin-treated rats. Morin exerts antihyperglycemic, antihyperlipidemic, and antioxidant activities in diabetic rats.

Spilanthes filicaulis (Schumach. & Thonn.) C. D Adam leaf extract prevents assault of streptozotocin on liver cells via inhibition of oxidative stress and activation of the NrF2/Keap1, PPARγ, and PTP1B signaling pathways.

Spilanthes filicaulis (Schumach. & Thonn.) C. D Adam is a shrubby plant of the Asteraceae family that has medicinal benefits for the pharmaceutical and cosmetic industries. The purpose of this study was to assess the effectiveness of Spilanthes filicaulis leaf extract in a streptozotocin (STZ)-induced rat model and the associated signaling pathways. A sample of 25 male Wistar rats was randomly assigned to groups I, II, III, IV, and V. Each group included five animals, i.e., control rats, diabetic control rats, diabetic rats treated with metformin, and diabetic rats treated with 150 mg/kg/bw and 300 mg/kg/bw of the methanolic extract of S. filicaulis leaves (MESFL). Treatment was administered for 15 successive days via oral gavage. After 15 days, the rats were evaluated for fasting blood glucose (FBG), glycated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (MDA), hexokinase, and glucose-6-phosphatase activities. Gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPAR-γ), kelch-like ECH-associated protein 1 (Keap1), protein tyrosine phosphatase 1B (PTP1B) and the antiapoptotic protein caspase-3 were examined. MESFL was administered to diabetic rats, and changes in body weight, fasting blood glucose (FBG) and HbA1c were restored. Furthermore, in diabetic rats, S. filicaulis significantly reduced the levels of triglycerides (TGs), total cholesterol (TC), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) and significantly increased HDL. S. filicaulis improved ALT, AST, and ALP enzyme activity in diabetic rats. MDA levels decreased considerably with increasing activity of antioxidant enzymes, such as GST, SOD, CAT and GSH, in diabetic liver rats treated with S. filicaulis. Diabetic rats treated with MESFL and metformin exhibited upregulated mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Kelch-like ECH-associated protein 1 (Keap1) and protein tyrosine phosphatase 1B (PTP1B) mRNA expression in the liver was downregulated in diabetic rats treated with MESFL and metformin. In addition, MESFL downregulated the mRNA expression of caspase-3 in diabetic rats. It can be concluded from the data presented in this study that MESFL exerts a protective effect on diabetic rats due to its antidiabetic, antioxidant, antihyperlipidemic and antiapoptotic effects and may be considered a treatment for T2DM.

Regulation of carbohydrate metabolism and insulin secretion in diabetic rats following treatment with Hypericum perforatum L. hairy root aqueous methanol extract

Hairy root (HR) cultures of Hypericum perforatum L. have shown promise in controlling hyperglycemia, regulating blood lipid and enzyme profiles, and improving metabolic function in vivo. These benefits are mainly attributed to the phenolic acids, flavonoids, and xanthones present in HR extracts. However, the specific mechanism underlying these effects remains unclear. This study was performed to elucidate the biochemical and molecular mechanisms driving HR the antihyperglycemic and antidiabetic effects of HR extracts. HR extract (200 mg/kg body weight) was administered daily for 14 days to healthy rats and rats with streptozotocin-induced diabetes, with glibenclamide serving as a positive control. The phenolic composition of the HR extracts was confirmed through high-performance liquid chromatography/diode array detection/electrospray ionization mass spectrometry (HPLC/DAD/ESI-MSn ) analysis. The results showed that HR extract treatment increased the plasma insulin level and pancreatic poly (adenosine diphosphate-ribose) polymerase (PARP) activity in diabetic rats, thus normalizing blood glucose levels. Additionally, it reduced the activity of gluconeogenic enzymes, increased the activity of glycolytic enzymes, and normalized the glycogen content in the liver. HR extract-treated rats also exhibited increased hepatic adenosine monophosphate-activated protein kinase (AMPK) mRNA expression and a decreased protein kinase Cε (PKCε) concentration. In conclusion, HR extract demonstrated insulinotropic effects and effectively regulated hepatic carbohydrate metabolism in diabetic rats by modulating AMPK expression and the PKCε concentration. These findings suggest the potential use of HR extract as an herbal medicine for diabetes treatment and a source of antidiabetic drug development.

Protective Effect of Betulin on Streptozotocin-Nicotinamide-Induced Diabetes in Female Rats.

Type 2 diabetes is characterized by hyperglycemia and a relative loss of β-cell function. Our research investigated the antidiabetic potential of betulin, a pentacyclic triterpenoid found primarily in birch bark and, intriguingly, in a few marine organisms. Betulin has been shown to possess diverse biological activities, including antioxidant and antidiabetic activities; however, no studies have fully explored the effects of betulin on the pancreas and pancreatic islets. In this study, we investigated the effect of betulin on streptozotocin-nicotinamide (STZ)-induced diabetes in female Wistar rats. Betulin was prepared as an emulsion, and intragastric treatments were administered at doses of 20 and 50 mg/kg for 28 days. The effect of treatment was assessed by analyzing glucose parameters such as fasting blood glucose, hemoglobin A1C, and glucose tolerance; hepatic and renal biomarkers; lipid peroxidation; antioxidant enzymes; immunohistochemical analysis; and hematological indices. Administration of betulin improved the glycemic response and decreased α-amylase activity in diabetic rats, although insulin levels and homeostatic model assessment for insulin resistance (HOMA-IR) scores remained unchanged. Furthermore, betulin lowered the levels of hepatic biomarkers (aspartate aminotransferase, alanine aminotransferase, and alpha-amylase activities) and renal biomarkers (urea and creatine), in addition to improving glutathione levels and preventing the elevation of lipid peroxidation in diabetic animals. We also found that betulin promoted the regeneration of β-cells in a dose-dependent manner but did not have toxic effects on the pancreas. In conclusion, betulin at a dose of 50 mg/kg exerts a pronounced protective effect against cytolysis, diabetic nephropathy, and damage to the acinar pancreas and may be a potential treatment option for diabetes.

Hypoglycemic, antidiabetic and toxicological evaluation of leaf extract of Xylopia parviflora (A. rich.) Benth

BackgroundAlmost all Xylopia species have a long history of being used therapeutically in China due to their potent antioxidant properties. Xylopia parviflora (X. parviflora) is a relatively novel plant comprised mainly of beta-pinene, which has a rich history in Chinese medicine and is a principal active constituent in numerous Chinese herbs such as Rakkyo, the Chinese onions, Huasi Baidu Fang and Ru Xiang which are all native to China. ObjectiveThe study evaluated the antidiabetic potentials of the methanol leaf extract of X. parviflora and its toxicity profile. MethodsA modified version of the OECD guidelines was used to conduct acute and sub-chronic toxicity tests on the plant extract. The extract's effects on glucose, haematological, and biochemical components were evaluated using standard procedures. Using glibenclamide (10 mg/kg) and distilled water as positive and negative controls, the extract was tested for its antidiabetic activity in diabetic rats with streptozotocin induction at 50, 150, and 300 mg/kg for 28 days. Furthermore, vital organs underwent histopathological examination. Analysis of Variance (ANOVA) and the Dunnett multiple comparison tests were used for the statistical analysis, with a significance level of p < 0.05 ResultsPreliminary phytochemical analysis of the leaf extract revealed the presence of tannins, flavonoids, saponins, alkaloids, terpenoids, deoxy-sugars, and anthraquinones. The extract's median lethal dose (LD50) was greater than 2000 mg/kg in mice. Although it significantly reduced blood glucose levels in normal rats at 150 and 300 mg/kg doses, it had no toxic effects on the haematological and biochemical components of the collected blood samples. The extract produced an antidiabetic, non-dose-dependent impact on day seven at all the tested doses in streptozotocin-induced rats. On days 14, 21, and 28, however, glibenclamide and extract activity at all tested doses were comparable. At 200 mg/kg, the extract did not affect the histology of the liver, brain, kidney, or pancreas, but at 400 and 800 mg/kg, it had a slight and severe impact on these organs, respectively. ConclusionAccording to the study's findings, X. parviflora has antihyperglycemic activity and is non-toxic at low doses but may be harmful at high doses.

Characterization and evaluation of the hepatoprotective activity of α-mangostin isolate in diabetic rats

Introduction: Isolation of α-mangostin (α-MG) from the rind extract of Garcinia mangostana L. showed antioxidant, anticancer, antidiabetic, and cytotoxic activities. The effectivity of a-mangosteen isolate compounds on hepatoprotective bioactivity in diabetic conditions has not been found. This study aimed to characterize α-MG isolate and evaluate its hepatoprotective activity in diabetic rats. Methods: This research was a post-test-only control group design. This study used 36 rats which were divided into 6 groups, namely positive control group, negative control group, standard drug group, and treatment group with α-MG dose of 10 mg/kg body weight, 30 mg/kg body weight, and 50 mg/kg body weight. Hepatoprotective evaluation parameters examined included levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin and liver histopathology observations. Test the effect on the study using the One-Way ANOVA test. Results: The results showed that a-mangosteen compound has a significant effect on levels of AST (p-value&lt;0.05), ALT (p-value&lt;0.05), ALP (p-value&lt;0.05), and total bilirubin (p-value&lt;0, 05), but there were no necrotic cells on the histopathological observation of the liver. Conclusion: α-mangostin isolate from Garcinia mangostana L. has the potential as hepatoprotective in diabetic rats.

Mango (Mangifera indica L.) seed kernel extract suppresses hyperglycemia by modulating pancreatic β cell apoptosis and dysfunction and hepatic glucose metabolism in diabetic rats.

This study investigated the anti-hyperglycemic action of mango seed kernel extract (MKE) and various mechanisms involved in its actions to improve pancreatic β cells and hepatic carbohydrate metabolism in diabetic rats. An intraperitoneal injection of 60mg/kg of streptozotocin (STZ) followed by 30 consecutive days of treatment with MKE (250, 500, and 1000mg/kg body weight) was used to establish a study group of diabetic rats. Using liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS/MS) for identification, 26 chemical compounds were found in MKE and the high-performance liquid chromatography (HPLC) analysis of the MKE also revealed the existence of mangiferin, gallic acid, and quercetin. The results confirmed that in each diabetes-affected rat, MKE mitigated the heightened levels of fasting blood glucose, diabetic symptoms, glucose intolerance, total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C). As demonstrated by a remarkable increment in serum and pancreatic insulin, the diabetic pancreatic β cell function was potentiated by treating with MKE. The effect of MKE on diabetic pancreatic apoptosis clearly reduced the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells, which was related to diminished levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and Bax and an increase in Bcl-xL protein expression. Furthermore, diabetes-induced liver damage was clearly ameliorated along with a notable reduction in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and abnormal liver histology. By enhancing anti-oxidant superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, MKE alleviated diabetes-induced pancreatic and liver oxidative damage, as demonstrated by diminished levels of malondialdehyde. In minimizing the expression levels of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase-1 proteins in the diabetic liver, MKE also enhanced glycogen content and hexokinase activity. Collectively, these findings indicate that by suppressing oxidative and inflammatory processes, MKE exerts a potent anti-hyperglycemic activity in diabetic rats which serve to protect pancreatic β cell apoptosis, enhance their function, and improve hepatic glucose metabolism.

The protective effect of Lemon Peel Essential Oil on Pancreas and Brain Oxidative Stress and Inflammation induced by Streptozotocin-Nicotinamide in rats: Behavioral and Biochemical Evidences

The objective of this study is to investigate the effects of Moroccan lemon peel essential oil (LPEO) on various aspects such as anti-hyperglycemic, anti-inflammatory, antioxidant, and anxiolytic activities in diabetic rats. The animals were divided into five groups: normal control group, diabetic control group, diabetic group treated with metformin (300mg/kg), and two diabetic groups treated with LPEO at doses of 0.6ml/kg and 1.2ml/kg, respectively. T2DM was induced in the rats by administering intraperitoneal injections of Streptozotocin and Nicotinamide. Treatment with LPEO or metformin was initiated immediately after confirming the presence of hyperglycemia and continued for a duration of four weeks. Anxiety-related behavior in the rats was assessed using two behavioral tests. 24 hours after conducting the behavioral tests, all rats were anesthetized, and blood samples were taken for the analysis of lipid parameters. The pancreas and brain were dissected to assess TNF-alpha, SOD, and MDA levels. Treatments with LPEO contributed significantly to the preservation of lipid profile and reduction of the atherosclerosis index in diabetic rats (p&lt;.05). Additionally, there was a notable decrease in MDA and TNF-α concentration in the pancreas and brain of diabetic rats treated with LPEO associated with a remarkable increase in SOD activity in the pancreas and brain compared to diabetic control group (p&lt;.05). Lastly, both LPEO and metformin treatments demonstrated significant improvements in anxiety-related behavior in this rat model (p&lt;.05). These positive effects could potentially be attributed to the potent antioxidant and anti-inflammatory activities of both treatments.

CCN1 inhibition affects the function of endothelial progenitor cells under high-glucose condition.

The impact of cysteine-rich angiogenic inducer 61 (Cyr61, also called CCN1) on endothelial progenitor cells (EPCs) from diabetic-rat-derived whole peripheral and bone marrow remains poorly understood. Therefore, the expression levels of CCN1, CCN1-induced C-X-C chemokine receptor type 4 (CXCR4), and stromal-cell-derived factor-1 (SDF-1) were explored under high glucose (HG) conditions. The aim of the study was to explore the effects of high CCN1 levels on EPC activity in diabetic rats through mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway modulation. Primary EPCs were isolated from bone marrow and whole peripheral blood of streptozocin (STZ)-induced diabetic Sprague-Dawley rats and controls. Cell migration, tube formation ability and viability were determined using transwell, Cell Counting Kit-8 (CCK-8), and Matrigel®-based capillary-like tube formation assays. Protein and gene expression levels were measured by western blot and real-time quantitative polymerase chain reaction (RT-qPCR). The study findings showed that EPC migration, viability and tube formation ability were significantly lower under HG conditions. High CCN1 expression levels restored EPC function by inducing SDF-1 and CXCR4 in EPCs under HG conditions. Furthermore, HG suppressed MEK/ERK phosphorylation, while an ERK1/2 agonist rescued EPC CCN1-SDF-1/CXCR4 expression under HG conditions through the activation of the MEK/ERK pathway. This study demonstrates that high CCN1 expression levels restored EPC functions, partly by modulating MEK/ERK signaling. These findings provide a basis for developing novel therapeutic methods for diabetic vascular neogenesis and vascular injury repair.

Gastroprotective evaluation of Medicago sativa L. (Fabaceae) on diabetic rats

Traditional uses for the plant Medicago sativa (M. sativa) (Alfalfa) (Family: Fabaceae) include liver protection, antioxidant activity, and the treatment of bleeding and digestive issues. This study aims to assess the effect of ethanol extract of M. sativa (EEMS) on experimental-induced ulcers in diabetic rats. By pylorus ligation and ethanol administration, gastric ulcers were induced in diabetic rats. Five groups each consisting of six rats in each model were used. All other groups except Group I were made diabetic by giving rats alloxan (140 mg/kg i.p.). Vehicles were given to Group I (normal control) and Group II (diabetes control) rats. Group III (positive control) received ranitidine 50 mg/kg, and Group IV and V received EEMS at doses of 100 and 400 mg/kg, respectively. In the pylorus ligation and ethanol-induced stomach ulcer model of rats, the findings demonstrated that EEMS (100 mg/kg) showed a decreased ulcer index of 2.01 ± 0.41 and was found statistically significant against the diabetes control group (p < 0.001) as well as, an ulcer index of 0.68 ± 0.22 by EEMS (400 mg/kg) with a significant reduction in the ulcer index (p < 0.001). EEMS (100 and 400 mg/kg) reduce free acidity by 13.16 ± 0.65 mEq/L and 9.83 ± 0.30 mEq/L, respectively. EEMS also showed a protective impact on the liver and kidneys of diabetic rats. Antihyperglycemic action was also discovered in diabetic animals. The findings of the current investigation demonstrated that ethanolic extract of M. sativa possesses anti-ulcer activity in diabetic rats. Ethanolic extract of M. sativa may be a treatment option for stomach ulcers that also have diabetes.

Forskolin Improves Male Reproductive Complications Caused by Hyperglycemia in Type 2 Diabetic Rats.

In many diabetic patients, spermatogenesis complications are frequent causing infertility problems. This study aimed to demonstrate the effect of Forskolin on male reproductive dysfunction caused by type 2 diabetes. In this experimental study, type 2 diabetes was induced by a high-fat diet (HFD) for one month and then a low single dose injection (35 mg/kg) of streptozotocin (STZ) in Wistar rats. After 72 hours, rats with more than 200 mg/dl of blood glucose were considered type 2 diabetic rats. Forty rats (200-250 g) were divided into four groups (n=10) including group 1 (G1): rats with normal diet and buffer citrate (STZ solvent) injection, group 2 (G2): control type 2 diabetic rats with HFD and STZ injection, group 3 (G3): type 2 diabetic rats received phosphate buffer saline (PBS) as Forskolin solvent, and group 4 (G4): Forskolin treated diabetic rats (10 mg/kg) for 1 month. In comparison to control group, in diabetic groups (G2 and G3) some parameters are increased significantly: The blood glucose (P=0.00078), testicular malondialdehyde (MDA) level and body weight (P=0.00009) and Bax gene expression (P=0.00007). Unlike, some parameters are decreased significantly: The serum level of testosterone (P=0.0009), testicular superoxide dismutase (SOD, P=0.00007) and glutathione peroxidase (GPX) levels (P=0.00008), sperm concentration (P=0.00008), motility (P=0.00009), normal morphological sperm (P=0.00008) and Bcl-2 gene expression (P=0.00009). However, in Forskolin treated group (G4) the parameters stayed close to control values that was significantly (P=0.00007) higher than in G2 and G3 groups. Therefore, treatment with Forskolin significantly improved these abnormal changes in Forskolin-treated group. Our study demonstrates that Forskolin is an effective antidiabetic agent, which significantly improves sperm concentration, testosterone levels, and antioxidant activity in diabetic rats.

Antihyperglycemic and antihyperlipidemic effects of Cymbopogon citratus leaves in dexamethasone-induced diabetic rats

Background: In sub-Saharan Africa, especially in Cameroon, different parts of Cymbopogon citrarus (C. citratus) are prescribed as remedies for diabetes mellitus and dyslipidemia. This study was designed to investigate the effects of hydroalcoholic extract of C. citratus (HACC) leaves in dexamethasone-induced-diabetic (Dex-db) rats. Materials and Methods: The HACC was obtained by decoction for 15 min by mixing 250 g of dry powder of the leaves of C. citratus by completing the total volume to 1L with a hydroalcoholic solution (water-ethanol, 30:70). After cooling to room temperature and filtration using Whatman No. 4 filter paper, the extract was concentrated using a rotary evaporator at 45 °C. Moderate diabetes was induced by daily subcutaneous injection of dexamethasone (5 mg/kg) once daily for 7 days. On the 8th day, the animals which have a blood glucose level greater than 120 mg/dL were selected and randomized into 5 groups of 5 animals each who received the different treatments for two weeks as follows: two negative control groups, negative normal control (NNC) and negative dexamethasone control (NDC) received only vehicle (distilled water); one positive control group received glibenclamide (5 mg/kg) and two groups received HACC at doses of 50 and 100 mg/kg respectively. On the other hand, compared to the NDC group, we observed a significant (P&lt;0.001) dose-response after 14 days of treatment a decrease in serum concentrations of TC, LDLc, and AI, and an increase in HDLc. A highly significant decrease (P&lt;0.001) was also observed in serum TG concentration but with a more pronounced action at the lowest dose of HACC (50 mg/kg). Results: After two weeks of administration of the HACC, we observed during the oral glucose tolerance test (OGTT) a highly significant rate of reduction in glycemia (%) at the two doses tested (50 and 100 mg/kg) compared to the NNC group (P&lt;0.001) 2 hours after glucose load, no significant difference was observed (P&gt;0.05). With regard to the serum lipid profile (total cholesterol (TC), HDL cholesterol (HDLc), triglycerides (TG), LDL cholesterol (LDLc) and atherogenicity index (AI)), after 14 days of administration of the various treatments, with the exception of the TC which decreased significantly (P&lt;0.001), no significant difference (P&gt;0.05) was observed on the other parameters in the animals having received the HACC only at the dose of 100 mg/kg compared to the NNC group. Conclusion: This finding suggests that the leaves of C. citratus have a highly significant antihyperglycemic and antihyperlipidemic activity in diabetic rats by preventing the postprandial glycemia peak and by readjusting the lipid profile, in particular by lowering serum LDL-cholesterol, triglycerides and the atherogenicity index.

The potential role of CpG oligodeoxynucleotides on diabetic cardiac autonomic neuropathy mediated by P2Y12 receptor in rat stellate ganglia.

Cardiac autonomic neuropathy has a high prevalence in type 2 diabetes, which increases the risk of cardiovascular system disorders. CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) ligand, has been shown to have cardioprotection and cellular protection. Our previous work showed that P2Y12 in stellate ganglia (SG) is involved in the process of diabetic cardiac autonomic neuropathy (DCAN). Here, we aim to investigate whether CpG-ODN 1826 plays a protective role in DCAN and whether this beneficial protection involves regulation of the P2Y12-mediated cardiac sympathetic injury. Our results revealed that CpG-ODN 1826 activated TLR9 receptor, improved the abnormal blood pressure (BP), heart rate (HR), heart rate variability (HRV) and sympathetic nerve discharge (SND) activity in diabetic rats and reduced the up-regulated NF-κB, P2Y12 receptor, TNF-α and IL-1β in SG. Meanwhile, CpG-ODN 1826 significantly decreased the elevated ATP, nuclear receptor coactivator 4 (NCOA4), iron, ROS and MDA levels and increased GPX4 and GSH levels. In addition, CpG-ODN 1826 contributes to maintain normalization of mitochondrial structure in SG. Overall, CpG-ODN 1826 alleviates the sympathetic excitation and abnormal neuron-glial signal communication via activating TLR9 receptors to achieve a balance of autonomic activity and relieve the DCAN in rats. The mechanism may involve the regulation of P2Y12 receptor in SG by reducing ATP release and NF-κB expression, which counteract neuroinflammation and ferroptosis mediated by activated P2Y12 in SG.