Levels In Diabetic Rats Research Articles

Semaglutide Ameliorates Diabetic Neuropathic Pain by Inhibiting Neuroinflammation in the Spinal Cord

Glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes and obesity. Despite the development of several drugs for neuropathic pain management, their poor efficacy, tolerance, addiction potential, and side effects limit their usage. Teneligliptin, a DPP-4 inhibitor, has been shown to reduce spinal astrocyte activation and neuropathic pain caused by partial sciatic nerve transection. Additionally, we showed its capacity to improve the analgesic effects of morphine and reduce analgesic tolerance. Recent studies indicate that GLP-1 synthesized in the brain activates GLP-1 receptor signaling pathways, essential for neuroprotection and anti-inflammatory effects. Multiple in vitro and in vivo studies using preclinical models of neurodegenerative disorders have shown the anti-inflammatory properties associated with glucagon-like peptide-1 receptor (GLP-1R) activation. This study aimed to investigate the mechanism of antinociception and the effects of the GLP-1 agonist semaglutide (SEMA) on diabetic neuropathic pain in diabetic rats. Methods: Male Wistar rats, each weighing between 300 and 350 g, were categorized into four groups: one non-diabetic sham group and three diabetic groups. The diabetic group received a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 60 mg/kg to induce diabetic neuropathy. After 4 weeks of STZ injection, one diabetic group was given saline (vehicle), and the other two were treated with either 1× SEMA (1.44 mg/kg, orally) or 2× SEMA (2.88 mg/kg, orally). Following a 4-week course of oral drug treatment, behavioral, biochemical, and immunohistochemical analyses were carried out. The mechanical allodynia, thermal hyperalgesia, blood glucose, advanced glycation end products (AGEs), plasma HbA1C, and spinal inflammatory markers were evaluated. Results: SEMA treatment significantly reduced both allodynia and hyperalgesia in the diabetic group. SEMA therapy had a limited impact on body weight restoration and blood glucose reduction. In diabetic rats, SEMA lowered the amounts of pro-inflammatory cytokines in the spinal cord and dorsal horn. It also lowered the activation of microglia and astrocytes in the dorsal horn. SEMA significantly reduced HbA1c and AGE levels in diabetic rats compared to the sham control group. Conclusions: These results indicate SEMA’s neuroprotective benefits against diabetic neuropathic pain, most likely by reducing inflammation and oxidative stress by inhibiting astrocyte and microglial activity. Our findings suggest that we can repurpose GLP-1 agonists as potent anti-hyperalgesic and anti-inflammatory drugs to treat neuropathic pain without serious side effects.

Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review

The history of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is so long and started in 1835 when Petersen extracted a compound called phlorizin from apple tree bark. About fifty years later, von Mering discovered its glucosuric properties. In the 1980s, it was discovered that the glucosuria resulted from inhibition by phlorizin of glucose reabsorption by the renal tubules, which lowered blood glucose levels in diabetic rats. Nowadays, beyond their glucose-lowering effects, growing evidence suggests significant cardiorenal benefits associated with SGLT2i therapy. Indeed, several clinical trials, including landmark studies such as EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, have demonstrated robust reductions in cardiovascular events, particularly heart failure hospitalizations and cardiovascular mortality, among patients treated with SGLT2i. However, subsequent trials showed that SGLT2i benefits extend beyond the diabetic population, encompassing individuals with and without diabetes. Additionally, SGLT2i exhibit nephroprotective effects, manifesting as a slowing of the progression of chronic kidney disease and a reduction in the risk of end-stage kidney disease. The mechanisms underlying the cardiorenal benefits of SGLT2i are multifactorial and include improvements in glycemic control, reduction in arterial stiffness, modulation of inflammation and oxidative stress, reduction of intraglomerular pression and promotion of natriuresis and diuresis through inhibition of SGLT2 in the luminal brush border of the first segments of the proximal kidney tubule. This narrative review aims to explore the cardiorenal outcomes of SGLT2i, encompassing their mechanisms of action, clinical evidence, safety profile, and implications for clinical practice.

Combined Anti-Diabetic and Wound Healing Effects of Binahung Leaf (Basella rubra L.) and Snakehead Fish (Channa striata) Extracts in Alloxan-Induced High-Fat Diet Rats

Diabetes mellitus is a metabolic disease that continues to increase in the world. Lifestyle factors cause diabetes cases to increase uncontrollably. The development of medicines based on natural ingredients has become a subject of study for researchers throughout the world. Meanwhile, binahong leaf extract contains flavonoids and saponins, which can reduce the absorption of glucose. Snakehead fish extract containing albumin also influences the reduction of diabetic wounds. The combination of binahong and snakehead fish extract is expected to synergistically lower blood glucose levels and cure diabetic wounds. Therefore, this study aimed to determine the anti-diabetic and wound healing activity resulting from the combination of binahong leaf and snakehead fish extract in rat models of diabetes induced with alloxan and fat diet. The test animals were divided into six groups with five per group, namely normal, positive, and negative control, as well as dose 1 (snakehead fish 250 mg/kg and binahong extract 100 mg/kg), dose 2 (snakehead fish 250 mg/kg and binahong extract 300 mg/kg), and a single dose of snakehead fish extract 500 mg/kg. The experiment was conducted for 21 days by administering the test solution once a day. The results showed that administering a combination of binahong extract at a dose of 100 mg/kg and snakehead fish at a dose of 500 mg/kg significantly reduced blood glucose levels in diabetic rats (p≤0.05). Treatment using a combination of the two extracts was more effective in lowering blood sugar levels compared to a single dose of snakehead fish extract.

Effect of madecassic acid on retinal oxidative stress, inflammation and Growth Factors in streptozotocin-induced diabetic rats

Diabetic retinopathy (DR) is the leading cause of blindness and visual loss in people with diabetes. It has been suggested that the progression of DR is associated with chronic inflammation and oxidative stress. The aim of the present work was to evaluate the ability of the natural compound madecassic acid (MEA) to reverse the negative impact of streptozotocin (STZ) on retinal injury in rats. Diabetic rats induced by STZ were treated with MEA at the doses of 10 and 20 mg/kg bw for 8 weeks. The study compared the efficacy of the drug in controlling high blood sugar levels and its impact on therapeutic targets such as SOD, CAT, GPx, NF-κB, TNF-α, IL-6, IL-1β, VEGF, IGF, bFGF and Keap1/Nrf-2 pathway. The results showed that the treatment with MEA significantly restored the retinal SOD, CAT, and GPx levels in diabetic rats to the near-normal levels. Moreover, the level of inflammatory mediators (TNF-α, IL-1β, IL-6) and growth factors (VEGF, IGF, bFGF) was significantly lower in retinas of animals treated with MEA as compared to retinas of diabetic animals. The study also established that MEA administration reduced the NF-κB protein and altered the Nrf-2/Keap1 pathway thereby reducing oxidative stress and inflammation. Furthermore, the use of MEA prevented the progression of the retinal capillary basement membrane thickening. It has been found that MEA offers significant protection to the retina and therefore, the compound may be useful in the treatment of DR in humans.

Metformin and Caffeine’s Influence on Lipid Profile Indices of Streptozotocin-Induced Dyslipidemia in an Animal Model

Dyslipidemia has been linked to insulin resistance and hyperglycemia. Hyperglycemia, which is the outcome of either insufficient insulin production or insensitivity to insulin, is the hallmark of diabetes mellitus (DM). In this study, thirty-six (36) male Wistar rats with diabetes induced by streptozotocin were used to determine the effect of metformin and caffeine on blood glucose levels and lipid profile indices. The rats weighed between 150 and 200 grams and were split into six groups of six animals each at random. Group A was given unlimited access to chow (Grower feed) and water adlibitum. Group B was administered 60 mg/kg of streptozocin (STZ) without any medication, while Group C was given 60 mg/kg of STZ together with 50 mg/kg of metformin. Groups D and E were administered 60 mg/kg of streptozocin and 25 mg/kg and 50 mg/kg of caffeine, for a duration of 21 days respectively. Group F was given 50 mg/kg of caffeine together with 50 mg/kg of metformin for a duration of 21 days. After performing a post-hoc LSD comparison and using ANOVA to analyze the results, the lipid profile and blood glucose level were deemed significant at p<0.05. A paired t-test was used to analyze body weight. Rats with diabetes had reduced body weight, whereas those receiving metformin and caffeine treatments had noticeably increased body weight. The findings demonstrated that whereas metformin and caffeine therapy greatly reduced blood glucose levels, STZ caused hyperglycemia in group B. However, diabetic rats had considerably higher levels of triglycerides (TG) and total cholesterol (TC), which were reduced by metformin and caffeine administration. HDL activity was considerably increased after treatment with metformin and caffeine, despite the rats' reduced HDL levels in group B. Rats with diabetes had considerably elevated levels of LDL and VLDL, and therapy with metformin and caffeine markedly restored their activity. The study shows that caffeine plus metformin may be utilized to control the lipid profile and blood glucose levels in diabetic rats.

Leptin and Insulin Interaction Modulates Pancreatic Nitric Oxide Levels in Diabetic Rats

Leptin and Insulin Interaction Modulates Pancreatic Nitric Oxide Levels in Diabetic Rats

Comparing the Impact of Continuous Endurance and High-intensity Interval Training on Cecal Butyrate and Propionate Levels in Diabetic Rats Induced by High-fat Diet

Background: Dysbiosis and metabolic disorders of the microbiota, often caused by an imbalance in the intestinal microbial composition, are significant issues linked to immobility, obesity, and diabetes. Physical exercise is recognized for its role in managing these symptoms by regulating the composition and metabolites of the intestinal microbiota, thereby improving gut health and overall metabolic function. Objectives: This study aimed to investigate and compare the effects of continuous endurance training (CET) and high-intensity interval training (HIIT) on two key cecal microbiota metabolites, butyrate and propionate, in diabetic rats. Methods: Forty-five male Wistar rats were made diabetic by a high-fat diet and were trained under CET and HIIT exercise protocols. Cecal tissue samples were taken from the rats to evaluate the effect of exercise, and the levels of two microbial metabolites, butyrate and propionate, were measured using the high-performance liquid chromatography (HPLC) method. Results: Among the exercise patterns studied, HIIT significantly improved the concentrations of butyrate and propionate, while CET showed no effect on these metabolites. Conclusions: Our findings suggest that, unlike CET, HIIT may effectively mitigate metabolic disturbances resulting from gut dysbiosis in diabetic patients. However, any definitive conclusion about the effects of CET and HIIT exercises on intestinal microbial metabolites necessitates further comprehensive tests on other metabolites and an examination of additional supporting evidence, such as changes in the composition of the intestinal microbiome.

Effects of Sargassum Glaucescens Algae on Blood Glucose Level in Diabetic Rats With a High-Fat Diet and Streptozotocin

Background: Diabetes medications can have dramatic effects on controlling the disease and achieving the therapeutic goals of people with diabetes, but most of them have side effects. Given the role of brown algae in maintaining blood glucose levels, their investigation can provide valuable information for the control and treatment of type 2 diabetes (T2D). Accordingly, this study investigated the effect of Sargassum glaucescens on blood glucose levels in diabetic rats. Materials and Methods: Forty-six randomly selected rats were assigned to five groups. The control group was fed the normal diet, and diabetic rats were induced by streptozotocin (STZ) and a high-fat diet (HFD). The other groups included the diabetes+low dose insulin group, diabetes+high dose insulin, and diabetic rats that received Sargassum Glaucescens 20% alga powder added to fatty food. Weekly blood glucose, hemoglobin A1c (HbA1c), the amount of drinking water, food consumed, urine volume, glucose tolerance test (GTT), and insulin tolerance test (ITT) underwent measurement. Results: The mean of ITT in the diabetic group was significantly higher than in the control group (P=0.001), which indicates insulin resistance in these groups. The lowest blood glucose concentration was in the high-dose insulin group; weekly blood glucose, GTT, ITT, and HbA1c in the alga group did not change compared to diabetes. However, some indicators, such as HbA1c, were better in the group receiving algae than in the low-dose insulin group. The weight of the group receiving algae increased until the third week, but it decreased after that, and at the end of the study, it was lower in this group than in the control group (P<0.001). Conclusion: The study findings revealed that Sargassum Glaucescens algae had no significant effect on serum glucose, GTT, ITT, or HbA1c in the studied rats.

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.

Physicochemical, microbiological, and sensory properties of healthy juices containing aloe vera gel and probiotics and their antidiabetic effects on albino rats.

The consumption of fruit and vegetable juices is widely recognized as a healthy choice across all age groups. Orange, carrot, and aloe vera are renowned for their functional properties and health benefits. In this study, we investigated the potential incorporation of aloe vera gel into blended orange and carrot juices. We also evaluated the resulting mixed probiotic juices (chemical, microbiological, and sensory aspects) during a 14-day storage period at refrigerator temperature. The chemical composition and phytochemical structure of aloe vera gel were examined, followed by an assessment of the biological effects of these healthy juices on diabetic albino rats. The results indicated improvements in total soluble solids, reducing sugars, and total sugars with increasing storage duration. Furthermore, the study demonstrated that incorporating aloe vera into the natural mixed juices enhanced their phytochemical quality. The treatment supplemented with aloe vera gel gave the highest total content of phenolic and flavonoid substances, which were 310 mg of GAE/100 g and 175 mg of quercetin/100 g, respectively. Probiotic strains (Bifidobacterium animalis subsp lactis Bb12, Lactiplantibacillus plantarum 299V, and Lactobacillus acidophilus L10) exhibited good viable cell counts in orange and mixed orange and carrot probiotics juices with viable counts of 7.42-8.07 log CFU/mL. Regarding sensory attributes, the study found that increasing the ratio of orange juice improved the taste while increasing the ratio of carrot juice enhanced the color in juice mixtures. Incorporation of aloe vera into mixed natural juices also enhanced the reduction of blood glucose, triglyceride, cholesterol, LDL, creatinine, ALT, AST, and urea levels while increasing total protein and HDL levels in diabetic rats. Based on these findings, oranges, carrots, and aloe vera offer the potential to produce new, flavorful, nutritious, and appealing juices. Moreover, this study determined that a functional juice with favorable sensory properties can be created by blending 75% orange juice, 20% carrot juice, and 5% aloe vera gel. Additionally, aloe vera demonstrated greater efficacy as an antidiabetic agent in rats. Further research is suggested to explore the potential advantages of aloe vera gel and probiotic juices in mitigating diabetes and other metabolic syndromes.

EFFECTIVITY TEST OF THE COMBINATION OF ETHANOL EXTRACT MAHKOTA DEWA FRUIT (Phaleria macrocarpa (Scheff.) Boerl.) WITH METFORMIN TO LOWERING BLOOD GLUCOSE LEVELS IN ALLOXAN-INDUCED WISTAR WHITE RATS STRAIN

Metformin is a first-line biguanid drug for type 2 of diabetes mellitus. Metformin potentially causes liver fibrosis in long-term use, its decrease it in their effectiveness of antidiabetic. Combining metformin with antidiabetic a-glucosidase enzyme inhibitors can increase the effectiveness of metformin. Mahkota dewa fruit is a natural ingredient that has antidiabetic activity with the mechanism of action of inhibiting a-glucosidase enzyme. This study aims to determine the effect of the combination of mahkota dewa fruit extract (EEMF) with metformin on the effectiveness of reducing blood glucose levels in diabetic rats. A total of 20 rats were grouped into 4, namely, group I: given distilled water (negative control); group II: given metformin 45 mg/kgBW; group III: given EEMF 50 mg/kgBW; group IV: given a combination of metformin 45 mg/kgBW and EEMF 50 mg/kgBW. The study was conducted by determining blood glucose levels using the GOD-PAP method. The results showed that the combination of EEMF with metformin had an average decrease per day from after induction to day 7 of 42,9 mg/dL and from day 7 to day 14 of 0,45 mg/dL. It can be concluded that the combination of EEMF dose 50 mg/kgBW with metformin 45 mg/kgBW is not recommended to be used together, because the large decrease has the risk of hypoglycemia effect. Keywords: antidiabetic, alloxan, metformin, fruit of mahkota dewa.

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.

Tauroursodeoxycholic Acid (TUDCA) Relieves Streptozotocin (STZ)-Induced Diabetic Rat Model via Modulation of Lipotoxicity, Oxidative Stress, Inflammation, and Apoptosis.

Tauroursodeoxycholic acid (TUDCA) is approved for the treatment of liver diseases. However, the antihyperglycemic effects/mechanisms of TUDCA are still less clear. The present study aimed to evaluate the antidiabetic action of TUDCA in streptozotocin (STZ)-induced type 2 diabetes mellitus (T2DM) in rats. Fifteen adult Wistar albino male rats were randomly divided into three groups (n = five in each): control, diabetic (STZ), and STZ+TUDCA. The results showed that TUDCA treatment significantly reduced blood glucose, HbA1c%, and HOMA-IR as well as elevated the insulin levels in diabetic rats. TUDCA therapy increased the incretin GLP-1 concentrations, decreased serum ceramide synthase (CS), improved the serum lipid profile, and restored the glycogen content in the liver and skeletal muscles. Furthermore, serum inflammatory parameters (such as TNF-α, IL-6, IL-1ß, and PGE-2) were substantially reduced with TUDCA treatment. In the pancreas, STZ+TUDCA-treated rats underwent an obvious enhancement of enzymatic (CAT and SOD) and non-enzymatic (GSH) antioxidant defense systems and a marked decrease in markers of the lipid peroxidation rate (MDA) and nitrosative stress (NO) compared to STZ-alone. At the molecular level, TUDCA decreased the pancreatic mRNA levels of iNOS and apoptotic-related factors (p53 and caspase-3). In conclusion, TUDCA may be useful for diabetes management and could be able to counteract diabetic disorders via anti-hyperlipidemic, antioxidant, anti-inflammatory, and anti-apoptotic actions.

Apigenin potentiates glucose-stimulated insulin secretion through the PKA-MEK kinase signaling pathway independent of K-ATP channels

AimApigenin, a natural bioflavonoid, is reported as an anti-diabetic agent since it possesses the ability to inhibit α-glucosidase activity, cause stimulation of insulin action and secretion, manage ROS, and prevent diabetes complications. Apigenin was identified as a new insulin secretagogue that enhances glucose-stimulated insulin secretion and seems like a better antidiabetic drug candidate. Here we explored the insulinotropic mechanism(s) of apigenin in vitro in mice islets and in vivo in diabetic rats. MethodsSize-matched pancreatic islets were divided into groups and incubated in the presence or absence of apigenin and agonists or antagonists of major insulin signaling pathways. The secreted insulin was measured by ELISA. The intracellular cAMP was estimated by cAMP acetylation assay. The acute and chronic effects of apigenin were evaluated in diabetic rats. Resultsapigenin dose-dependently enhanced insulin secretion in isolated mice islets, and its insulinotropic effect was exerted at high glucose concentrations distinctly different from glibenclamide. Furthermore, apigenin amplified glucose-induced insulin secretion in depolarized and glibenclamide-treated islets. Apigenin showed no effect on intracellular cAMP concentration; however, an additive effect was observed by apigenin in both forskolin and IBMX-induced insulin secretion. Interestingly, H89, a PKA inhibitor, and U0126, a MEK kinase inhibitor, significantly inhibited apigenin-induced insulin secretion; however, no significant effect was observed by using ESI-05, an epac2 inhibitor. Apigenin improved glucose tolerance and increased glucose-stimulated plasma insulin levels in diabetic rats. Apigenin also lowered blood glucose in diabetic rats upon chronic treatment. ConclusionApigenin exerts glucose-stimulated insulin secretion by modulating the PKA-MEK kinase signaling cascade independent of K-ATP channels.

Antidiabetic Effects of Foeniculum vulgare in Alloxan-induced Diabetic Male Rats

Background & objective: Diabetes mellitus (DM) has become one of the most challenging health problems of the 21st century. Foeniculum vulgare (Mouri in Bengali), an ancient culinary herb, is known to reduce blood glucose levels thus reducing the risk of diabetes. This study was done to observe the antidiabetic role of Mouri in alloxan-induced diabetic male rats. Methods: This experimental study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC), Dhaka from July 2018 to June 2019. A total of 30 healthy Wistar albino male rats, 90-120 days old, weighing between 150-180g were included in the study. After acclimatization for 14 days, they were divided into two groups: the control group (Group A) and the experimental group (Group B – diabetic rats treated with Mouri). The control group was again subdivided into Group A1 (normal control group) and Group A2 (alloxan-induced diabetic control group). Each of these groups consisted of 10 rats. All the rats received a basal diet for 21 days. In addition to the basal diet, Group A2 and Group B received a single intraperitoneal injection of alloxan 140 mg/kg on day 1 to induce diabetes. Moreover, Group B received Mouri extract 150 mg/kg/day orally for 21 consecutive days starting from day 1 of the study period. After 12 hours of fasting, blood samples were collected from the tail veins of every rat on day 1 for estimation of Fasting Blood Glucose (FBG) and serum ALT levels. On day 4 FBG levels of all the rats were measured once again. Then all the rats were sacrificed on day 22 and their blood samples were collected from the heart. The outcome variables, such as FBG level, serum levels of insulin, were measured and compared among the study groups. The pancreatic tissue was also collected and histopathology was done by standard laboratory procedure to study their histologic architecture. Result: In this study, fasting blood glucose level in diabetic rats treated with Mouri at the endpoint of the study (on day 22) was significantly lower (5.51 ± 0.47 mmol/L) than that in alloxan-induced diabetic control (13.52 ± 0.76 mmol/L) (p < 0.001) and was almost equal to that in normal control (5.38 ± 0.55 mmol/L) (p = 0.891). The serum insulin level in diabetic rats treated with Mouri (11.52 ± 0.84 mmol/L) was almost similar to that of normal control (12.46 ± 1.07 mmol/L) on day 22, whereas it was much higher than that in alloxan-induced diabetic control (8.51 ± 0.68 mmol/L) (p < 0.001). Histological study of pancreases of the rats, revealed extravasation of blood in the pancreatic acini, reduced area of islets of Langerhans with atrophy, vacuolation, degeneration, and pyknosis of β-cell nuclei and centrilobular necrosis in the alloxan-induced diabetic control rats. Conclusion: Mouri (Foeniculum vulgare) improves the glycemic status of the alloxan-induced diabetic rats. Ibrahim Card Med J 2023; 13 (1&2): 53-59

Comprehensive chemical profiling with UHPLC-MS, in-vitro, in-silico, and in-vivo antidiabetic potential of Typha domingensis Pers; A novel source of bioactive compounds

Aim of studyTypha is one of the valuable plant genera in folklore use in diabetes, and it can be a good source of bioactive chemicals. The current project was planned to investigate the pharmaceutical potential of n-butanol fraction of Typha domingensis Pers. (TDBF), a less explored medicinal plant. Materials and methodsThe phytochemical composition of the TDBF was assessed through a comprehensive analysis, encompassing the quantification of total bioactive contents (including total tannins and HPLC-PDA quantification) and a thorough exploration of secondary metabolites through scanning with UHPLC-MS. The pharmacological assessment included the determination of antioxidant activity (Total Antioxidant Capacity and Metal Chelating Assay), hemolytic potential, in-vitro antidiabetic effects (α-glucosidase and α-amylase inhibition, and antiglycation activity), as well as in-vivo antidiabetic activities. Molecular docking and ADMET studies were also performed for UHPLC-MS identified compounds. ResultsThe TDBF showed 134.76 ± 8.23 mg TAE/g total tannin contents. With HPLC-PDA, p-Hydroxy benzoic acid and p-Coumaric acid were quantified. During UHPLC-MS scanning, a total of five bioactive metabolites were identified in the negative mode, while 54 were detected in the positive mode. The in-vivo assessment of antidiabetic activity revealed a notable reduction in blood glucose levels in diabetic rats following treatment with the extract, demonstrating its efficacy compared to the control groups. Furthermore, the extract exhibited a positive impact on renal and liver function, evidenced by lowered levels of serum urea, ALT, ALP, creatinine, and a decrease in serum cholesterol levels. ConclusionThe results of this study showed that Typha domingensis Pers. possesses a variety of bioactive compounds and demonstrates notable potential in regulating diabetes. The study recommends further investigation into isolating these bioactive phytochemicals for their potential therapeutic applications across various diseases.

TGR5, GLP-1, and GIP expression in diabetic Wistar rats in response to Ficus exasperata vahl leaf extract

BackgroundDiabetes mellitus remains a critical global health issue, driving the need for continual exploration of new therapeutic strategies. Ficus exasperata Vahl, renowned for its extensive ethnomedicinal use, holds promise as a potential remedy for diabetes. However, its precise mechanisms of action in managing diabetes remain unclear. This study aimed to investigate the impact of Ficus exasperata Vahl leaf extract (MEFE) on the expression of TGR5, GLP-1, and GIP in diabetic Wistar rats. MethodUsing methanol extraction, Ficus exasperata was processed and characterized through GC–MS analysis. Twenty rats were divided into four groups: diabetic untreated, normal control, diabetes treated with MEFE (200 mg/kg), and diabetes treated with insulin (0.3 units). Diabetes induction utilized alloxan monohydrate (150 mg/kg, intraperitoneal), followed by daily treatments for 28 days. Blood glucose and insulin levels were assessed via glucose oxidase and ELISA, while antioxidant enzyme activities (SOD, catalase, GPx) and total protein were measured using randox kits. Gene expression of GLP-1, TGR5, and GIP was quantified through qPCR. In silico docking of MEFE compounds to the P2Y1 receptor was conducted using Cavity-detection guided blind-docking software. Pancreatic islet histology was examined with hematoxylin and eosin stains, and statistical significance was determined with GraphPad Prism (p < 0.05). ResultThe GC–MS analysis identified 23 constituents in MEFE, with kaur-16-ene exhibiting the highest binding affinity (-8.2 Kcal) against the P2Y1 receptor. Significant reductions in blood glucose levels were observed in the MEFE-treated diabetic group, accompanied by increased expression of insulin, TGR5, GLP-1, GIP, SOD, catalase, and GPx compared to the untreated diabetic group. Additionally, MEFE treatment facilitated the regeneration of pancreatic islet cells. ConclusionThese findings suggest that MEFE exerts antioxidative effects and stimulates genes crucial for controlling blood glucose levels in diabetic rats.

Rosa canina extract relieves methylation alterations of pancreatic genes in STZ-induced diabetic rats : Gene methylation in diabetic rats treated with an extract.

Diabetes is a chronic metabolic disease that affects many parts of the body. Considering diabetes as a beta cells' defect and loss, the focus is on finding mechanisms and compounds involved in stimulating the function and regeneration of pancreatic β-cells. DNA methylation as an epigenetic mechanism plays a pivotal role in the β-cells' function and development. Considering the regenerative and anti-diabetic effects of Rosa canina extract, this study aimed to assess the methylation levels of Pdx-1, Pax-4, and Ins-1 genes in diabetic rats treated with Rosa Canina extract. Streptozotocin-induced diabetic rats were used to evaluate the frequency of Pdx-1, Pax-4, and Ins-1 gene methylation. Treatment groups were exposed to Rosa canina as spray-dried and decoction extracts. Following blood glucose measurement, pancreatic DNA was extracted and bisulfited. Genes' methylation was measured using MSP-PCR and qRT-PCR techniques. Oral administration of Rosa canina extracts significantly reduced blood sugar levels in diabetic rats compared to the control group. The methylation levels of the Pdx-1, Pax-4, and Ins-1 genes promoter in streptozotocin-induced diabetic rats increased compared to the control rats while, the treatment of diabetic rats with Rosa canina extracts, spray-dried samples especially, led to a decreased methylation in these genes. The results of this study showed that Rosa canina extract as a spray-dried sample could be effective in treating diabetes by regulating the methylation of genes including Pdx-1, Pax-4, and Ins-1 involved in the activity and regeneration of pancreatic islet cells.

FORMULATION AND EVALUATION OF Β-SITOSTEROL LOADED NIOSOMES FOR ENHANCED ANTIDIABETIC ACTIVITY: A POTENTIAL ALTERNATIVE IN TYPE 2 DIABETES MANAGEMENT

Niosomes, vesicles formed by non-ionic surfactants, offer advantages in drug delivery by enhancing solubilization and encapsulating both lipophilic and hydrophilic drugs. This study focuses on β-sitosterol-loaded niosomes designed to protect its anti-diabetic properties. Formulated with Span™ 60, Span™ 80 and cholesterol, the niosomes showed high entrapment efficiency (90%) and favorable release kinetics. Stability studies confirmed their robustness in various conditions. In vivo experiments demonstrated significant improvements in body weight and blood glucose levels in diabetic rats. The optimized formulation (NF8) exhibited controlled release and substantial antidiabetic activity, suggesting its potential as an effective treatment for type 2 diabetes mellitus.

Impact of various dietary lipids on amelioration of biomarkers linked to metabolic syndrome in both healthy and diabetic Wistar rats

BackgroundThe present study was designed to investigate the influence of different dietary lipids (sheep’s fat, olive oil, coconut oil, and corn oil) on specific biomarkers associated with metabolic syndrome in both healthy and diabetic rats.MethodsThe study designed for 45 days, utilized a male diabetic wistar rat (body weight, 180–220 g) model induced by streptozotocin (45 mg/kg bw). The rats were divided into two sections: five non-diabetic and five diabetic groups, each containing six rats. The first group in each section serving as the control, received a standard diet. Both non-diabetic or diabetic groups, were provided with a standard diet enriched with 15% sheep fat, 15% coconut oil, 15% olive oil, and 15% corn oil, respectively for a duration of 45 days.ResultsPost-supplementation, both healthy and diabetic control rats exhibited a higher food intake compared to rats supplemented with lipid diet; notably food intake was higher in diabetic control than healthy control. However, rats fed with coconut oil, olive oil and sheep fat showed weight gain at the end of the experiment, in both healthy and diabetic groups. Coconut oil supplementation significantly (p ≤ 0.05) increased HDL-C and total cholesterol level in diabetic groups compared to healthy group, it was confirmed by an increased PPAR-α and ABCA-1 protein level. Olive oil significantly decreased triglyceride, total cholesterol, and LDL-C levels in diabetic rats when compared to sheep fat or coconut oil. Corn oil significantly decreased fasting glucose, total cholesterol and LDL-C levels compared to all other groups. Corn and olive oil supplemented normal groups, found with significant increase in hepatic glucose-lipid oxidative metabolism associated protein, like FGF-21, MSH, ABCA-1, PPAR-γ and decreased lipogenesis proteins like, SREBP and PPAR-α levels. In contrast, sheep grease and coconut oil increased SREBP and PPAR-α expression in both normal and diabetic groups. Most notably, normal and diabetic groups pretreated with sheep grease resulted in increased inflammatory (MCP-1, IL-1β, TLR-4, TNF-α), and oxidative stress markers (LPO, GSH, GPx, SOD and CAT) linked with metabolic complications.ConclusionThe combination or alternative use of olive oil and corn oil in daily diet may play a significant role in preventing proinflammatory condition associated with insulin resistance and cardiovascular diseases.