Potent Antihyperglycemic Effect Research Articles

Synergistic modulation of endoplasmic reticulum stress pathway, oxidative DNA damage and apoptosis by β-amyrin and metformin in mitigating hyperglycemia-induced renal damage using adult zebrafish model

Diabetic nephropathy (DN) can be prevented with early therapeutic intervention in diabetic patients. Recent investigations suggest that β-amyrin, a pentacyclic triterpenoid, could offer significant benefits with its potential antihyperglycemic and nephroprotective effects. We investigated the protective effects of β-amyrin alone and combined it with metformin, the cornerstone therapy for diabetes, using a hyperglycemic adult Zebrafish (ZF) model. The ZF were subjected to hyperglycemia by immersing them in 111 mM glucose solutions. Treatment efficacy was assessed by measuring serum glucose and insulin levels and antioxidant, ER stress, apoptosis, and proinflammatory markers. ZF kidneys were also studied for immunohistochemistry and histopathology. Results revealed that the combined treatment of β-amyrin and metformin resulted in a significant decrease (p ≤ 0.05) in blood glucose levels to 104.54 ± 1.63 mg/dL, in comparison to 388.75 ± 4.32 mg/dL in the untreated diseased control group. The reduction in hyperglycemia was more pronounced than treatment with either compound alone. Moreover, treatment with the combination restored renal function in diseased ZF, leading to significantly lower (p ≤ 0.05) serum urea (SU: 19.57 ± 1.61 mg/dL) and serum creatinine (SC: 0.56 ± 0.02 mg/dL) values compared to treatment with β-amyrin (SU:27.02 ± 0.96 mg/dL; SC: 0.7 ± 0.01 mg/dL) or metformin (SU: 24.53 ± 1.29 mg/dL; SC: 0.6 ± 0.02 mg/dL) alone. The treatment also reduced oxidative stress markers, apoptosis and ER stress markers, and proinflammatory cytokines. Histopathological analysis showed improved renal architecture with significantly lower (p ≤ 0.05) renal tubular injury scores with the combination than with individual treatment. This study provides novel insights into the combined therapeutic effects of β-amyrin and metformin in mitigating hyperglycemia-induced renal damage through key molecular pathways, highlighting a potentially effective therapeutic strategy for diabetic nephropathy. The findings hold promising translational relevance for developing combination therapies aimed at improving clinical outcomes in diabetic nephropathy patients.

Efficacy of nanoencapsulated Moringa oleifera L. seeds and Ocimum tenuiflorum L. leaves extracts incorporated in functional soft cheese on streptozotocin-induced diabetic rats

BackgroundIn recent years, there has been significant interest in using various plant-based phytochemicals with exceptional biological activities as nutraceuticals to prevent the development and advancement of diabetes mellitus and its severe consequences. The extracts of Moringa oleifera L. seeds and Ocimum tenuiflorum L. leaves are used in herbal therapy due to their beneficial effects in combating various disorders, notably diabetes mellitus PurposeThe paper aimed to investigate the incorporation of both free Moringa oleifera L. seed extract and Ocimum tenuiflorum L. leaves extract and nanoencapsulated using whey protein isolate cold gelation ultra-filtration cheese as natural plant-based functional foods and explore both free and nano-encapsulated ultra-filtration cheese impacts as a novel application on diabetic rats through nutritional parameters, biochemical parameters, physicochemical parameters, and sensory evaluation. MethodsThirty-six male Sprague-Dawley rats were given only one dose of streptozotocin (35 mg/kg body weight) intraperitoneally. The nutritional and biochemical parameters were assessed. The Moringa oleifera L. seed extract and Ocimum tenuiflorum L. leaves extract were successfully encapsulated, and the best ratio added was 75 mg of both, which gave the best results regarding particle size distribution, surface charge and encapsulation efficiency. ResultsThe Moringa oleifera L. seed extract and Ocimum tenuiflorum L. leaves extract gave the best results regarding particle size distribution, surface charge, and encapsulation efficiency. Their nano-encapsulated forms had increased the total solids, protein, and ash of ultra-filtration cheese. Moringa oleifera L. seed extract and Ocimum tenuiflorum L. leaves extract, nano-encapsulated in ultra-filtration cheese, gave antioxidant activity stability and significantly captured free radicals. The ultra-filtration cheese samples' sensory qualities evaluations received high marks and were suitable for incorporating Moringa oleifera L. seed extract and Ocimum tenuiflorum L. leaves extract nanoparticles in food systems. ConclusionThe nutritional and biochemical parameters confirmed that both nanoencapsulation forms of natural plant sources and functional soft cheese containing nano-encapsulated Moringa oleifera L. seed extract and Ocimum tenuiflorum L. leaves extract demonstrated a potential anti-hyperglycemic effect without any problems.

Punica granatum Bioactive Compounds-Loaded Chitosan Nanoparticles Exhibit Potent Antihyperglycemic Effect in Alloxan-Induced Diabetic Mice

In the current study, alloxan-induced diabetic mice model was used to assess the antihyperglycemic effects of Chitosan Nanoparticles (CSNP) loaded with (Punica granatum methanol extract-PG) bioactive compounds. Analysis of P. granatum extract revealed significant concentrations of various classes of polyphenols. In particular, the total polyphenols content is noted at 289.6 ± 5.1 mg/g, while flavonoids and anthocyanins exhibited concentrations of 53.7 ± 0.8 mg/g and 34.8 ± 0.4 mg/g, respectively. Chitosan nanoparticles were prepared by ionic gelation technique using TPP as crosslinking agent. Their spectroscopic characterization showed a good stability, high encapsulation efficiency and the bioactive molecule-loaded CNPs were well-dispersed with homogeneous distribution in the nanosolutions. In vivo experiments showed that when compared to the diabetic control group, diabetic mice treated with CSPG-CNP (100 mg/kg bw) displayed a significant decrease in their mean fasting blood glucose levels. Moreover, hepatic and kidneys histopathological examination showed clear improvements in hepatic alterations in animals treated with CSPG-CNP compared to diabetic control group. Indeed, hepatic cells regained normal size, hepatic steatosis decreased, and the number of inflammatory cells was drastically reduced, suggesting effectiveness of this combination in improving diabetes-induced hepatic lesions. Moreover, mice of CSPG-CNP group showed significant improvements in renal alterations with signs of renal tissue repair. Indeed, damage to Bowman's capsule, glomeruli, and renal tubules were improved, returning to normal renal histology.

Eco-friendly Nanoparticles Synthesized from Salvia sclarea Ethanol Extract Protect against STZ-induced Diabetic Nephropathy in Rats via Antioxidant, Anti-inflammatory, and Apoptosis Mechanisms.

Recent global scientific attention has been directed towards eco-friendly synthesis and versatile applications of silver nanoparticles (AgNPs) due to their effectiveness against specific cells and tissues. This study aimed to develop a green synthesis method for AgNPs using ethanolic extract from Salvia sclarea aerial parts, and to assess their protective efficacy against streptozotocin (STZ)-induced diabetic nephropathy in rats. Additionally, antioxidant, anti-inflammatory, and apoptosis studies were conducted to understand their mode of action. Characterization via ultraviolet-visible (UV-Vis) spectroscopy, infrared (IR) spectroscopy, and X-ray diffraction (XRD) confirmed the formation of ethanol extract of Salvia sclarea silver nanoparticles (EESS AgNPs), with a distinctive absorption peak at 400 nm. Scanning electron microscopy (SEM) analysis revealed predominantly spherical and quasi-spherical shapes of the synthesized nanoparticles. The treatment procedure spanned for a period of 12 weeks in diabetic rats and were evaluated for inflammatory markers (tumor necrosis factor-α, antioxidant markers (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH) and apoptosis markers (Bcl-2, Bax, cleaved-caspase-3). Results demonstrated that treatment with EESS AgNPs significantly reduced blood glucose levels compared to the diabetic group. Additionally, EESS AgNPs treatment led to a significant decrease in levels of pro-inflammatory cytokines TNF-α, IL-1β, and PKC-ꞵ in renal cells. Furthermore, EESS AgNPs effectively modulated antioxidant enzyme concentrations, including GSH, SOD, GPx, and CAT, bringing them to acceptable levels. Administration of EESS AgNPs also resulted in a significant decrease in protein levels of Bax and activated caspase-3, while increasing expression of the anti-apoptotic protein Bcl-2 in renal cells of STZ-induced diabetic rats. In conclusion, EESS AgNPs demonstrate potent anti-hyperglycemic effects, potentially mitigating diabetic nephropathy by suppressing hyperglycemiainduced oxidative stress, apoptosis, and inflammation in renal cells of diabetic rats.

Screening of Selected Cultivars of Sweet Sorghum for Phytochemicals and In vitro Evaluation of Their Antihyperglycemic and Cytotoxic Activity

Background: Sorghum, a wonder millet, is well known for its beneficial phytochemical profiles. In comparative terms, juice from sweet sorghum has better commercial potential as syrup in several food-based applications. Various sweet sorghum differs in their profile of various phytochemicals, which can impact the commercial potential of sweet sorghum juice. Methods: Our previous works on cultivars developed at ICAR-IIMR were screened for phytochemical, sugar and mineral profile. To give a holistic view of the phytochemical profile of sweet sorghum varieties, the present study is attempted to evaluate the total phenolic and flavonoid content, antihyperglycaemic and cytotoxic profile of the components present in the varieties CSV19SS, SSV84, SSV74. The phytochemical footprint of sweet sorghum juice was studied through HRLCMS. Results: The results showed ethyl acetate extract of SSV84 having potential antihyperglycemic effects with an IC50 of 22.156 ± 0.9 µg/ml (α-glucosidase) and 0.070 ± 0.02 mg/ml (α-amylase) with a comparatively higher phenolic (232.6 ± 1 mg GAE/g) and flavonoid (138.18 ± 0.9 mg QE/g) content. The chloroform extract of SSV 84 showed a higher cytotoxic effect at an IC50 of 165.502 ± 7 µg/ml (HeLa cells) and 237.895 ± 15 µg/ml (Hep G2 cells). HRLCMS profile of SSV 84 showed the presence of long-chain fatty acids in hexane extract. Anthraquinones, carotenoids, xanthophylls, cinnamic acid and derivatives, and isoflavones were present in chloroform extract, while Ethyl acetate extract was rich in phenolic acids and also consisted of coumarins, quinones, alkaloids, and terpenoids. Conclusion: The high cytotoxic and antihyperglycemic activities of extracts can be attributed to the presence of these phytochemicals.

Effects Of Psidium Guajava Crude Leaf Methanol-Extract On Lowering Blood Sugar Levels In Rat

Blood sugar levels, or blood glucose levels, are crucial for overall health and are regulated by the pancreas through insulin. Normal blood sugar levels range between 70-99 mg/dL when fasting and up to 140 mg/dL two hours after eating. Abnormal blood sugar levels can suggest a variety of health issues, including hypoglycemia (low blood sugar levels caused by excess insulin, certain drugs, or illnesses such as diabetes) and hyperglycemia (high blood sugar levels associated with diabetes). Regular blood sugar monitoring is necessary, especially for diabetics. Guava, a tropical fruit, includes a variety of phytochemicals that have been linked to pharmacological benefits such as antibacterial capabilities. This research uses an extraction process involving solid-liquid extraction or maceration, with methanol being the optimal solvent. The extract yields 9.51%. Wistar rats are used to investigate its antidiabetic efficacy. The rats are divided into three groups: positive control, negative control, and extract treatment. Diabetes is induced by subcutaneous injection of Alloxan, followed by oral administration of the methanol extract. Blood glucose levels are assessed after fasting for 6-8 hours. The extract from dried Guava leaf powder yields a concentrated extract with a 9.51% yield. In vivo assessments showed a significant reduction in blood glucose levels in rats treated with guava leaf extract, suggesting potential anti-hyperglycemic effects. The phenolic compounds in guava leaves contribute to antioxidant and anti-hyperglycemic effects. The study highlights the potential therapeutic effects of guava mint leaves and their extract components for diabetes management and antioxidant health benefits.

Dose-dependent anti-hyperglycemic & anti-dyslipidemic potential of aqueous leaves extract of Typha elephantina in-vivo and in-vitro

Diabetes mellitus is among the fundamental causes of illness and millions of deaths around the globe are directly attributed to it each year. Current antidiabetic medications often lack sustained glycemic control and carry significant risks of side effects. As a result, the use of plant-based treatments has gained popularity. In this experimental study, we evaluated the aqueous extracts (LQE) of Typha elephantina (also known as Elephant grass) leaves collected from freshwater marshes, for their potential anti-hyperglycemic and anti-hyperlipidemic antioxidant effects in healthy streptozotocin caused diabetic-mice. We employed glucose adsorption tests at different glucose levels and glucose diffusion tests to assess the in-vitro antidiabetic action of plant extract. For the in-vivo trail, we measured fasting blood glucose (FBG), glucose tolerance (GTT), as well as long-term anti-diabetic, anti-hyperlipidemic, and antioxidant activities. Our results from the glucose diffusion test indicated that the extract was highly effective at both low glucose concentrations (5 mmol L) and high glucose concentrations (100 mmol L). However, the glucose-diffusion ability reached its peaked at an excessively high dosage of the aqueous extract, suggesting a dose-related effect. Similarly, we observed that high doses of TEL.AQ extracts (400 mg/kg body weight) significantly reduced blood glucose levels in healthy mice during the glucose tolerance test (GTT) at 3 h and fasting blood glucose studies (FBG) at 6 h. Furthermore, the high-dose TEL.AQ extract effectively reduced liver-related serum markers and blood-glucose concentration (BGC) in severely chronic diabetic rats. The extract dosage also influenced lipid profile, conjugate and unconjugated bilirubin levels, cholesterol, triglycerides, HDL, and total bilirubin levels. Additionally, after administering a high extract dose, we observed considerable improvement in the liver homogenate markers CAT, POD, and SOD. In contrast, the extract at a low dosage(100 mg/kg),showed minimal, while a moderate dose (200 mg/kg), yielded promising results.

Anti-Hyperglycemic Effects of Bioactive Compounds in the Context of the Prevention of Diet-Related Diseases.

Diet-related diseases are health conditions primary caused by poor nutrition. These diseases encompass obesity, type 2 diabetes, cardiovascular diseases, osteoporosis, and certain types of cancer. Functional foods and nutraceuticals offer a promising dietary approach to addressing diet-related diseases across various clinical contexts. The bioactive compounds found in these foods are the subject of intensive studies aimed at discovering their anti-hyperglycemic effects, which are beneficial in alleviating chronic diseases and protecting human health. Hyperglycemia is a common risk factor for metabolic disease and mortality worldwide. Chronic hyperglycemic states can lead to many long-term complications, such as retinopathy, neuropathy, kidney disease, heart disease, cancer, and diabetes. This review explores the potential anti-hyperglycemic effects of bioactive compounds, specifically flavonoids and phenolic acids, and their proposed roles in mitigating chronic diseases and promoting human health. By thoroughly examining the existing literature, we investigated the potential anti-hyperglycemic effects of these bioactive compounds and their proposed roles in managing chronic diseases. The goal of this paper was to enhance our comprehension of how these compounds modulate glucose transporters, with the ultimate aim of identifying effective strategies for the prevention and treatment of diet-related diseases. Overall, this review investigated the use of bioactive compounds from functional foods as potential inhibitors of glucose transporters in the context of prevention/treatment of diet-related diseases.

Hypoglycemic and Antihyperglycemic Potential of Flavonoid Fraction from Citrus sinensis (L.) Osbeck in Normoglycemic and Diabetic Rats

Diabetes is one of the most prevalent diseases worldwide, and the search for therapeutic alternatives in developing countries has been focused on natural products, primarily from plants. This study evaluated the antihyperglycemic and hypoglycemic activities of the albedo (FA) and flavedo (FF) flavonoid fractions obtained from orange peels (often discarded) in normoglycemic Wistar rats. The flavonoid fractions were identified and quantified using HPLC-UV-DAD and compared with glibenclamide, repaglinide, saxagliptin, and acarbose. Additionally, both fractions were tested in a streptozotocin (65 mg/kg)/nicotinamide (100 mg/kg)-induced diabetic model. In normoglycemic rats, the highest glucose variation (%VG) occurred during the first hour after FA (112.8%) and FF (105.30%) administration at 100 mg/kg, indicating a hypoglycemic effect. In diabetic rats, FF at 100 mg/kg showed the highest %VG (140.41%) during the first hour after administration. HPLC-UV-DAD analysis revealed the presence of hesperidin (HSP) and naringenin (NGN), with the highest concentrations found in FA (HSP: 41.41%; NGN: 10.75%). These findings suggest potential antihyperglycemic effects of FA and FF fractions, possibly attributed to the presence of HSP and NGN. The results obtained in this work lay the foundations to explore the therapeutic applications of orange peels for controlling hyperglycemia in diabetes. In conclusion, our results suggest a reevaluation and revalorization of orange peels, as they contain pharmaceutically relevant flavonoids.

Antihyperglycemic effect of extra virgin sacha inchi oil in type 2 diabetic rats: Mechanisms involved in pancreatic β-cell function and apoptosis

Background and aimThe purpose of the study was to investigate the anti-hyperglycemic effect of extra virgin sacha inchi oil (EVSIO) and its possible mechanisms and actions against pancreatic β-cell death and dysfunction in type 2 diabetic (T2D) rats. Experimental procedureT2D rats were induced with a high-fat diet and low-dose of streptozotocin. The rats were then treated for 5 weeks with EVSIO (0.5, 1, and 2 ml/kg), or pioglitazone. Biochemical and histopathological studies, oxidative and inflammatory markers, and expression of apoptotic-related proteins were then evaluated. ResultsEVSIO treatment exhibited a dose-dependent reduction of fasting blood glucose, area under the curve of glucose, total cholesterol, and triglyceride levels in the diabetic rats, while improved pancreatic β-function was demonstrated by increasing pancreatic and serum insulin levels. EVSIO treatment effectively lowered atrophic pancreatic islets and reduced the level of serum and pancreatic MDA in the diabetic rats. In addition to serum and pancreatic GPx activities in the diabetic rats, EVSIO also augmented serum SOD. Increased levels of NF-κB, TNF-α and IL-6 present in the diabetic rats were greatly reduced by EVSIO treatment. Furthermore, EVSIO revealed an anti-apoptotic effect on the diabetic rat pancreas by upregulating Bcl-2, and downregulating Bax and cleaved caspase-3 protein expression. ConclusionThe overall study results demonstrated the potential anti-hyperglycemic effect of EVSIO in the diabetic rats. The beneficial effects of EVSIO may be attributed to its ability to improve pancreatic β-cell function and ameliorate β-cell apoptosis by inhibiting oxidative stress and inflammatory cytokines.

Insight into biological activities of chemically characterized extract from Marrubium vulgare L. in vitro, in vivo and in silico approaches.

Aqueous extracts of Marrubium vulgare L. (M. vulgare) are widely used in traditional medicine for their therapeutic effects. Hence, this study aims to evaluate in vitro, in vivo, and in silico the biological activities of M. vulgare aqueous extract to further support their traditional use. Qualitative phytochemical tests of M. vulgare extracts showed the presence of primary and secondary metabolites, while quantitative analyses recorded revealed the contents of total phenols, flavonoids, and tannins, with values of 488.432 ± 7.825mg/EAG gallic acid extract/g, 25.5326 ± 1.317mg/EQ Quercetin extract/g and 23.966 ± 0.187mg/EC catechin extract/g, respectively. Characterization of the phytochemical constituents of the extract revealed the presence of catechin and maleic acid as the most abundant while the evaluation of the antioxidant power revealed that the extract possesses significant antioxidant capacity, antimitotic potential, and antimicrobial properties against Streptococcus agalactiae and Staphylococcus epidermidis among many others. The antidiabetic activity of the extract showed a potent antihyperglycemic effect and a significant modulation of the pancreatic α-amylase activity as revealed by both in vitro and in vivo analysis, while an in silico evaluation showed that chemicals in the studied extract exhibited the aforementioned activities by targeting 1XO2 antimitotic protein, W93 antidiabetic protein and 1AJ6 antimicrobial protein, which revealed them as worthy of exploration in drug discovery odyssey. Conclusively, the result of this study demonstrates the numerous biological activities of M. vulgare and gives credence to their folkloric and traditional usage.

Comparative Antihyperglycemic and Antihyperlipidemic Effects of Lawsone Methyl Ether and Lawsone in Nicotinamide-Streptozotocin-Induced Diabetic Rats.

Our previous study uncovered potent inhibitory effects of two naphthoquinones from Impatiens balsamina, namely lawsone methyl ether (2-methoxy-1,4-naphthoquinone, LME) and lawsone (2-hydroxy-1,4-naphthoquinone), against α-glucosidase. This gave us the insight to compare the hypoglycemic and hypolipidemic effects of LME and lawsone in high-fat/high-fructose-diet- and nicotinamide-streptozotocin-induced diabetic rats for 28 days. LME and lawsone at the doses of 15, 30, and 45 mg/kg, respectively, produced a substantial and dose-dependent reduction in the levels of fasting blood glucose (FBG), HbA1c, and food/water intake while boosting the insulin levels and body weights of diabetic rats. Additionally, the levels of total cholesterol (TC), triglycerides (TGs), high-density lipoproteins (HDLs), low-density lipoproteins (LDLs), aspartate transaminase (AST), alanine transaminase (ALT), creatinine, and blood urea nitrogen (BUN) in diabetic rats were significantly normalized by LME and lawsone, without affecting the normal rats. LME at a dose of 45 mg/kg exhibited the most potent antihyperglycemic and antihyperlipidemic effects, which were significantly comparable to glibenclamide but higher than those of lawsone. Furthermore, the toxicity evaluation indicated that both naphthoquinones were entirely safe for use in rodent models at doses ≤ 50 mg/kg. Therefore, the remarkable antihyperglycemic and antihyperlipidemic potentials of LME make it a promising option for future drug development.

Insights on the Hypoglycemic Potential of Crocus sativus Tepal Polyphenols: An In Vitro and In Silico Study.

Post-prandial hyperglycemia typical of diabetes mellitus could be alleviated using plant-derived compounds such as polyphenols, which could influence the activities of enzymes involved in carbohydrate digestion and of intestinal glucose transporters. Here, we report on the potential anti-hyperglycemic effect of Crocus sativus tepals compared to stigmas, within the framework of valorizing these by-products of the saffron industry, since the anti-diabetic properties of saffron are well-known, but not those of its tepals. In vitro assays showed that tepal extracts (TE) had a greater inhibitory action than stigma extracts (SE) on α-amylase activity (IC50: TE = 0.60 ± 0.09 mg/mL; SE = 1.10 ± 0.08 mg/mL; acarbose = 0.051 ± 0.07) and on glucose absorption in Caco-2 differentiated cells (TE = 1.20 ± 0.02 mg/mL; SE = 2.30 ± 0.02 mg/mL; phlorizin = 0.23 ± 0.01). Virtual screening performed with principal compounds from stigma and tepals of C. sativus and human pancreatic α-amylase, glucose transporter 2 (GLUT2) and sodium glucose co-transporter-1 (SGLT1) were validated via molecular docking, e.g., for human pancreatic α-amylase, epicatechin 3-o-gallate and catechin-3-o-gallate were the best scored ligands from tepals (-9.5 kcal/mol and -9.4 kcal/mol, respectively), while sesamin and episesamin were the best scored ones from stigmas (-10.1 kcal/mol). Overall, the results point to the potential of C. sativus tepal extracts in the prevention/management of diabetes, likely due to the rich pool of phytocompounds characterized using high-resolution mass spectrometry, some of which are capable of binding and interacting with proteins involved in starch digestion and intestinal glucose transport.

Fixed-ratio combinations of basal insulin and glucagon-like peptide-1 receptor agonists as a promising strategy for treating diabetes.

The maintenance of appropriate glycemic control is important for the prevention of diabetic complications in people with type 2 diabetes (T2D). Numerous oral antidiabetic drugs are now clinically available, but in particular, the introduction of injection regimens using insulin and/or glucagon-like peptide-1 receptor agonist (GLP-1RA)s represents promising step-up options for oral antidiabetic drug treatment. The recently licensed fixed-ratio combination (FRC) products, which comprise basal insulin and a GLP-1RA, have potent anti-hyperglycemic effects and reduce the undesirable side-effects of each component, such as body weight gain, hypoglycemia, and gastrointestinal symptoms. Two FRCs-insulin degludec/Liraglutide and insulin glargine/Lixisenatide-are now clinically available and, to date, several phase II/III trials have been conducted in particular groups of subjects with T2D. However, their utility in real-world clinical settings is of interest for most clinicians. Recently reported real-world clinical trials of these two FRCs in various situations have demonstrated their efficacy regarding glycemic control and the quality of life of people with T2D. Their long-term safety and efficacy require confirmation, but a treatment strategy that includes an FRC may be compatible with the concept of "well-balanced" therapy in certain groups of patients with T2D who have inadequate glycemic control.

Effect of nano-encapsulated food flavorings on streptozotocin-induced diabetic rats.

Flavors and aromas are widely used in food and pharmaceutical industries to enhance food palatability. However, it is worth noting that they may also have bioactivity. This study aims to examine the potential impact of key flavors and their nanocapsules on health and diseases, such as type 2 diabetes mellitus (T2DM). The 36 nanocapsules of key flavorings were prepared by high shear homogenization (HSH). Seventy-two male Sprague-Dawley rats received a single dosage of streptozotocin (35 mg kg-1 body weight) intraperitoneally. All of the nutritional and biochemical parameters were statistically analyzed. A virtual docking study was conducted. Linalool nanoemulsion results showed the highest encapsulation efficiency (86.76%), while isoamyl acetate nanoparticles showed the lowest (69.99%). According to GC-MS analysis, encapsulation did not affect the flavoring structure with particle size distributions ranging from 277.3 to 628.8 nm. Using TEM, nanoemulsion particles appeared spherical with a desired nanometric diameter size. In the oral glucose tolerance test, flavorings in oil and nanoforms had no discernible hypoglycemia effects in normal rats. The nutritional and biochemical parameters confirmed that both normal and nanoencapsulation forms demonstrated a potential anti-hyperglycemic effect, and enhanced the rat health compared to the raw flavorings. The studied flavorings and their nanocapsules seem to have the potential double effect of a flavor compound as a food palatability enhancer with a potential beneficial effect on type 2 diabetes mellitus without any health drawbacks.

Co-administration of Spondias mombin and Metformin mitigates Streptozotocin-induced hepatorenal injury

BackgroundAs a result of its many therapeutic properties, including its potent anti-hyperglycemic effect, the Spondias mombin plant is quickly gaining popularity as a local therapeutic agent for the treatment of many ailments. This work aimed at investigating the effects of co-administration of Spondias mombin and metformin in STZ-induced hyperglycemia and hepatorenal injury in the Wistar rat model, specifically focusing on the morphological, biochemical, and immunohistochemical alterations in the liver and kidney. MethodsHundred healthy adult male Wistar rats weighing (80-150g) and assigned into 10 groups (A-J) (n= 10 each). The normal control group A received a single dose of citrate buffer (1mL/kg, p.o) while groups B, C, D, E, F, and I were induced with hyperglycemia by administering a single dose of Streptozotocin (60 mg/kg, i.p). Group B was left untreated while others were treated with Spondias mombin (600 mg/kg p.o), (400 mg/kg p.o), (200 mg/kg p.o), metformin (12.5 mg/kg p.o), and Spondias mombin + metformin (12.5 mg/kg) respectively. Groups G and H were administered Spondias mombin only (400 mg/kg) and metformin (12.5 mg/kg) respectively; and group J was not induced but administered both Spondias mombin only (400 mg/kg) and metformin (12.5 mg/kg). Administration in all groups lasted for 28 days. Rats were sacrificed and the liver and renal tissues were excised for histopathological examination using the H&E stain, while the Periodic acid Schiff reagent, and Masson Trichome stains were employed for connective tissue assessments. Oxidative stress parameters (CAT, SOD, GSH, and MDA) were evaluated. The assessment of liver enzymes (ALT, AST, and ALP) and renal markers (Urea, and Creatinine) were also carried out. Kidney and liver Bcl-2 expressions were assessed immunohistochemically. The data obtained were analyzed by ANOVA and Duncan Multiple Range post hoc test and presented as mean ± SEM at p <0.05. ResultsFollowing STZ induction, there were histopathological alterations in the renal and liver tissues while Spondias mombin treatment and combined Spondias mombin treatments with metformin mitigated these alterations. Anti-oxidant enzyme markers; CAT, SOD activities, and GSH level significantly decreased (p<0.05) while MDA increased significantly. Markers of liver injury; AST, ALT, and ALP were significantly increased (p < 0.05) in the STZ-only group while Spondias mombin treatment and combined Spondias mombin and metformin restored these changes. In the same manner, serum urea and creatine levels were significantly increased (p < 0.05) while Spondias mombin treatment and combined Spondias mombin and metformin ameliorated this. Immunohistochemical observations showed upregulated expressions of Bcl-2 in the liver rather than the kidney ConclusionsBased on the findings from this research is the phytomedicinal drug potential of Spondias mombin viz-a-viz MTF and the establishment of the combined actions of Spondias mombin and MTF . Co-administration of Spondias mombin and metformin mitigated Streptozotocin-induced hepatorenal histopathological alterations via anti-hyperglycaemic, anti-oxidative and anti-apoptotic potentials in the liver.

Antihyperglycemic effect of aqueous extract of Tetraclinis articulata in streptozotocin-induced diabetic rats and acute toxicity analysis.

The study aimed to evaluate the glucose-lowering effect of Tetraclinis articulata. Tetraclinis articulata is commonly used for the treatment of diabetes characterized by chronic hyperglycemia. This work aimed to evaluate the effect of Tetraclinis articulata (T. articulata) aqueous extract (TAAE) on glycaemia and lipid profile in normal and streptozotocin(STZ)-induced diabetic rats. Additionally, its acute toxicity, phytochemical composition, and antioxidant capacity were assessed. To highlight the effect of TAAE on plasma glucose levels and lipid metabolism, blood glucose levels were measured at 1, 2, 4, and 6 hours of treatment for the acute test and on days 2, 4 and 7 over the daily oral administration for the subchronic test at two selected doses (10 mg/kg and 20 mg/kg). Furthermore, Triglycerides (TGs), total cholesterol (TC), and High-density lipoprotein cholesterol (HDL-c) were measured after the treatment. The rats' liver, extensor digitorum longus (EDL), and soleus muscle were isolated from diabetic rats treated with TAAE at a dose of 20 mg/kg at the end of the experiment to measure glycogen content using a standard method. The acute toxicity of TAAE was examined according to the OECD guideline. In addition, body weight, signs of toxicity, and/or mortality were observed for 14 days. Besides, a preliminary phytochemical screening, quantification of phenolic, flavonoid, and tannin contents as well as the antioxidant activity were evaluated. The results showed that TAAE at the doses of 10 and 20 mg/kg possesses a potent antihyperglycemic effect in STZ-treated diabetic rats and an acute hypoglycemic effect in normal rats, as well as, the extract provoked a decrease of blood glucose levels after glucose loading in the glucose tolerance test in a dose-dependent manner. TAAE at a dose of 20 mg/kg revealed a significant improvement of the lipid profile. However, treatment with TAAE at a dose of 20 mg/kg did not significantly modify the glycogen content. In the same way, the acute toxicity analysis revealed no death or signs of toxicity in rats, and the LD50 value was more than 2 g/kg. In addition, preliminary phytochemical screening revealed that TAAE revealed the presence of polyphenols, flavonoids, tannins, carbohydrates, saponins, quinones, sterols and terpenoids. Furthermore, TAAE exhibited a potent antioxidant activity which may be due to the richness in polyphenol content (756.21±6.72 mg GAE/1 g of extract). The current study demonstrates for the first time that aqueous Tetraclinis articulata extract has a potent the glucose-lowering effect.

A Review of Anti-hyperglycemic Effects of Curry Leaf Tree (Murraya koenigii)

Diabetes mellitus is becoming a metabolic disease that is defined by the level of hyperglycemia. Nowadays, it has a serious threat to public healthiness in throughout the world. Constituents and extracts isolated from diverse natural resources, mainly plants, have constantly been a rich store for controlling and treating diabetes problems. Numerous researches are ongoing to identify the suitable traditional medical drugs, medicinal herbs, and resources for managing this condition. Murraya koenigii Spreng (family Rutaceae) is commonly known as a ‘curry leaf tree’ locally. It is widely scattered in India and Sri Lanka, and leaves are commonly used for cooking. And also mainly used for various health conditions such as diabetes, anemia, diarrhea, and others. The present review aimed to critically review the anti-hyperglycemic effect of the M. koenigii based on the review, in vitro, in vivo, and clinical studies. Based on this review, the M. koenigii possess flavonoids, phenols, saponins, alkaloids, tannins, and cardiac glycosides. It has shown a potential anti-hyperglycemic effect on induced diabetic rats. This review reported the potential of M. koenigii and its extract to be a high-value dietary product in terms of its anti-hyperglycemic effects and industrial profits. Therefore, the present review supports the researchers and readers/users to realize the importance of using M. koenigii in managing diabetes mellitus. Further, this review provides a valuable document for future scientific-related clinical trials in diabetic patients.

The Antidiabetic Effects and Modes of Action of the Balanites aegyptiaca Fruit and Seed Aqueous Extracts in NA/STZ-Induced Diabetic Rats.

Diabetes mellitus (DM) is a chronic metabolic disorder that threatens human health. Medicinal plants have been a source of wide varieties of pharmacologically active constituents and used extensively as crude extracts or as pure compounds for treating various disease conditions. Thus, the aim of this study is to assess the anti-hyperglycemic and anti-hyperlipidemic effects and the modes of action of the aqueous extracts of the fruits and seeds of Balanites aegyptiaca (B. aegyptiaca) in nicotinamide (NA)/streptozotocin (STZ)-induced diabetic rats. Gas chromatography–mass spectrometry analysis indicated that 3,4,6-tri-O-methyl-d-glucose and 9,12-octadecadienoic acid (Z,Z)- were the major components of the B. aegyptiaca fruit and seed extracts, respectively. A single intraperitoneal injection of STZ (60 mg/kg body weight (b.w.)) 15 min after intraperitoneal NA injection (60 mg/kg b.w.) was administered to induce type 2 DM. After induction was established, the diabetic rats were treated with the B. aegyptiaca fruit and seed aqueous extracts (200 mg/kg b.w./day) via oral gavage for 4 weeks. As a result of the treatments with the B. aegyptiaca fruit and seed extracts, the treated diabetic-treated rats exhibited a significant improvement in the deleterious effects on oral glucose tolerance; serum insulin, and C-peptide levels; liver glycogen content; liver glucose-6-phosphatase and glycogen phosphorylase activities; serum lipid profile; serum free fatty acid level; liver lipid peroxidation; glutathione content and anti-oxidant enzyme (glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase) activities; and the mRNA expression of the adipose tissue expression of the insulin receptor β-subunit. Moreover, the treatment with fruit and seed extracts also produced a remarkable improvement of the pancreatic islet architecture and integrity and increased the islet size and islet cell number. In conclusion, the B. aegyptiaca fruit and seed aqueous extracts exhibit potential anti-hyperglycemic and anti-hyperlipidemic effects, which may be mediated by increasing the serum insulin levels, decreasing insulin resistance, and enhancing the anti-oxidant defense system in diabetic rats.

Paracrine FGFs target skeletal muscle to exert potent anti-hyperglycemic effects

Several members of the FGF family have been identified as potential regulators of glucose homeostasis. We previously reported that a low threshold of FGF-induced FGF receptor 1c (FGFR1c) dimerization and activity is sufficient to evoke a glucose lowering activity. We therefore reasoned that ligand identity may not matter, and that besides paracrine FGF1 and endocrine FGF21, other cognate paracrine FGFs of FGFR1c might possess such activity. Indeed, via a side-by-side testing of multiple cognate FGFs of FGFR1c in diabetic mice we identified the paracrine FGF4 as a potent anti-hyperglycemic FGF. Importantly, we found that like FGF1, the paracrine FGF4 is also more efficacious than endocrine FGF21 in lowering blood glucose. We show that paracrine FGF4 and FGF1 exert their superior glycemic control by targeting skeletal muscle, which expresses copious FGFR1c but lacks β-klotho (KLB), an obligatory FGF21 co-receptor. Mechanistically, both FGF4 and FGF1 upregulate GLUT4 cell surface abundance in skeletal muscle in an AMPKα-dependent but insulin-independent manner. Chronic treatment with rFGF4 improves insulin resistance and suppresses adipose macrophage infiltration and inflammation. Notably, unlike FGF1 (a pan-FGFR ligand), FGF4, which has more restricted FGFR1c binding specificity, has no apparent effect on food intake. The potent anti-hyperglycemic and anti-inflammatory properties of FGF4 testify to its promising potential for use in the treatment of T2D and related metabolic disorders.