Streptozotocin-induced Hyperglycemic Rats Research Articles

Hypoglyceamic and Hepatoprotective Potentials of Dichloromethane (DCM) Fraction of Gongronema Latifolium Extract in Streptozotocin-Induced Diabetic Wistar Rats

Diabetes is a chronic health issue with devastating but preventable consequences. The increasing proportion of the aging population, intake of calorie-dense diets, weight problems and sedentary lifestyles have been directly implicated in the increased number of diabetics globally. Furthermore, diabetes confers a huge economic burden due to its management costs, especially in low income countries. This study investigated the hypoglyceamic and hepatoprotective potentials of the dichloromethane (DCM) fraction of G. latifolium stem bark extract on some biochemical parameters in streptozotocin-induced hyperglycemic rats. A total of thirty (30) Wistar rats were randomly assigned into five (5) groups with six (06) animals per group. Type 2 diabetes was induced with intraperitoneal administration of streptozotocin in Groups 2 – 4, with animals in Groups 1 and 2 acting as normal and untreated diabetic controls, respectively. Group 3 rats were treated with the standard drug, metformin, while groups 4 and 5 were orally administered 200 and 400 mg/kg body weight of DCM fraction of G. latifolium stem bark extract. Changes in the body weight, biochemical assays (ALT, AST, total protein, albumin and urea), and expression levels of selected genetic markers, as well as the changes in liver histology, were determined and compared. Data obtained from this study show that the fasting blood glucose levels in hyperglycemic rats were significantly (p < 0.05) reduced, and the body weight steadily increased in rats treated with both doses of the DCM fraction of G. latifolium stem bark extract compared to the untreated diabetic rats. Total protein, AST and ALT levels, but not albumin levels, were significantly (p < 0.05) increased in rats treated with both doses of the extract. In addition, administration of the extracts significantly (p < 0.05) reversed the streptozotocin-induced repression of NRF2 and CAT expression in diabetic rats. Furthermore, histology results show an improvement in the liver architecture in the rats treated with the extract. The results from this study show that the DCM fraction of g. Latifolium stem bark extract possesses hypoglycemic, hepatoprotective and anti-diabetic activities and could be used in the management of diabetes.

Hepatoprotective Mechanisms Induced by Spinach Methanolic Extract in Rats with Hyperglycemia-An Immunohistochemical Analysis.

Spinach methanolic extract (SME) has a hepatoprotective effect due to its polyphenolic antioxidants; however, its action in parenchymal (PQ) and non-parenchymal (nPQ) cells remains unknown. This study investigates the hepatoprotective effect of SME on streptozotocin-induced hyperglycemic rats (STZ), focusing on immunohistochemical analyses. Methods: The extract was prepared, and the total polyphenols and antioxidant activity were quantified. Adult male Wistar rats were divided into four groups (n = 8): normoglycemic rats (NG), STZ-induced hyperglycemic (STZ), STZ treated with 400 mg/kg SME (STZ-SME), and NG treated with SME (SME) for 12 weeks. Serum liver transaminases and lipid peroxidation levels in tissue were determined. The distribution pattern and relative levels of markers related to oxidative stress [reactive oxygen species (ROS), superoxide dismutase-1, catalase, and glutathione peroxidase-1], of cytoprotective molecules [nuclear NRF2 and heme oxygenase-1 (HO-1)], of inflammatory mediators [nuclear NF-κB, TNF-α], proliferation (PCNA), and of fibrogenesis markers [TGF-β, Smad2/3, MMP-9, and TIMP1] were evaluated. Results: SME had antioxidant capacity, and it lowered serum transaminase levels in STZ-SME compared to STZ. It reduced NOX4 staining, and lipid peroxidation levels were related to low formation of ROS. In STZ-SME, the immunostaining for antioxidant enzymes increased in nPQ cells compared to STZ. However, enzymes were also localized in extra and intracellular vesicles in STZ. Nuclear NRF2 staining and HO-1 expression in PQ and nPQ were higher in STZ-SME than in STZ. Inflammatory factors were decreased in STZ-SME and were related to the percentage decrease in NF-κB nuclear staining in nPQ cells. Similarly, TGF-β (in the sinusoids) and MMP-9 (in nPQ) were increased in the STZ-SME group compared to the other groups; however, staining for CTGF, TIMP1, and Smad2/3 was lower. Conclusions: SME treatment in hyperglycemic rats induced by STZ may have hepatoprotective properties due to its scavenger capacity and the regulation of differential expression of antioxidant enzymes between the PQ and nPQ cells, reducing inflammatory and fibrogenic biomarkers in liver tissue.

Local low-frequency vibration accelerates healing of full-thickness wounds in a hyperglycemic rat model.

Local low-frequency vibration (LLFV) promotes vasodilation and blood flow, enhancing wound healing in diabetic foot ulcers with angiopathy. However, vibration-induced vasodilation does not occur, owing to chronic hyperglycemia and inflammation. We hypothesized that LLFV improves glycometabolism and inflammation, leading to vasodilation and angiogenesis in diabetic wounds. Therefore, this study investigated the effect of LLFV on wound healing in hyperglycemic rats, primarily focusing on glycometabolism, inflammation, vasodilation, and angiogenesis. Streptozotocin-induced hyperglycemic Sprague-Dawley rats were used in this study. We applied LLFV to experimentally-induced wounds at 50 Hz and 0, 600, 1,000 or 1,500 mVpp for 40 min/day from post-wounding days (PWD) 1-14. The relative wound areas in the 600 and 1,000 mVpp groups on PWD 5-7 were significantly smaller than those at 0 mVpp. The expression of Glo-1 (1,500 mVpp) and Slc2A4 (1,000 and 1,500 mVpp) was upregulated on PWD 4 and 14, respectively. However, there was no difference in methylglyoxal expression levels in any group until PWD 14. At 1,000 mVpp, the expression of Tnfa on PWD 4, and that of Ptx3 and Ccl2 on PWD 14 was downregulated. Furthermore, the M1/M2 macrophage ratio was considerably decreased on both days. The expression of Nos3, Vegfa and vascular endothelial growth factor A was upregulated on PWD 4. In addition, vasodilation and angiogenesis were more obvious on PWD 14 with 1,000 mVpp. The results suggest that LLFV promotes wound healing, improves glycometabolism and inflammation, and enhances vasodilation and angiogenesis in hyperglycemic wounds.

Analysis of the ability of nano-mixture of Coriandrum sativum L. and Mimosa pudica L. leaves ethanol extract in lowering blood glucose and malondialdehyde (MDA) increased superoxide dismutase (SOD) in hyperglycaemic Wistar rats

Introduction: Nano-mixture chitosan was used as a nano-extract framework, while tripolyphosphate was used as a stabilizer. Coriandrum sativum L. and Mimosa pudica L. nano extracts were created using the ionic gelatin technique. This study aimed to evaluate the effect of nano-mixture herbal extract of Coriandrum sativum L. and Mimosa pudica L. to lower free radicals and glucose levels in streptozotocin-induced hyperglycaemic rats. Methods: Fourier transformation infrared (FTIR) characterized the resultant nano-mixture extract. The antihyperglycemic characteristics of a nano-mixture extract were investigated in streptozotocin-induced rats using a randomized post-test-only control group design. At the same time, blood glucose levels and oxidative stress markers MDA and SOD were monitored. Results: Coriandrum sativum L. and Mimosa pudica L. extracts included polyphenols, flavonoids, alkaloids, and terpenoids, according to the results of the phytochemical test. Nano extract was well supported by PSA characterization as a delivery vehicle for bioactive chemicals, with a zeta potential of -23.98 mV and a particle size of 422.20 nm. The oral administration of the nano-mixture extract at a dose of 50 mg/Kg BW/day had the greatest results for lowering glucose blood MDA and raising SOD levels in hyperglycaemic rats, according to the antihyperglycemic test on streptozotocin-treated rats. Conclusion: In hyperglycaemic rats, a nano-mixture of Coriandrum sativum L. and Mimosa pudica L. nano extract may lower MDA and blood glucose while raising SOD levels.

Nano extract of Coriandrum sativum l (ketumbar seed) decrease malondialdehyde (MDA) and blood glucose, and increase superoxide dismutase (SOD) in hyperglycaemic wistar rats

Introduction: Coriandrum sativum L (ketumbar seeds) nano extract was prepared using chitosan as a nano extract framework and tripolyphosphate as a stabilizer by ionic gelatin method. This study aimed to reduce free radicals in streptozotocin-induced hyperglycaemic rats by administering Coriandrum sativum L nano extract as nano herbal. Methods: Characterization of the resulting nano extract was performed using Fourier Transformation Infra-Red (FTIR). The ability of nano extract as antihyperglycemic on streptozotocin-induced rats was tested using the randomized post-test only control group design research by observing the levels of blood glucose, MDA, and SOD as markers of oxidative stress. Results: The phytochemical test showed that Coriandrum sativum L extracts contained polyphenols, flavonoids, alkaloids, and terpenoids. Characterization with PSA strongly supports nano extract as a delivery system for bioactive substances with a zeta potential of -25.80 mV and a particle size of 455.20 nm. The result of the antihyperglycemic test showed that oral administration at a dose of 50 mg/Kg BW/day gave the best result for decreasing glucose blood and MDA, and increasing SOD level in hyperglycaemic rats. LCMS/MS analysis showed that in ethanol extract of Coriandrum sativum L are suspected to contain the 7 compounds: DL-Valine, indoline, 2-quinolinol, trans-tnrthole, luteolin, apigenin, linoliamide, and luteolinin are compounds known in to be able to lower blood glucose and malondialdehyde. Conclusion: Coriandrum sativum L (ketumbar seeds) nano extract was prepared using chitosan had potential to decrease MDA and blood glucose, and increase SOD level in hyperglycaemic rats.

Antidiabetic and Toxicity Studies of the Extract of Four Nigerian Medicinal Plants

Aims: To evaluate the anti-hyperglycaemic efficacy and safety of the methanol extract of the combination of Senecio biafrae leaf, Xylopia aethiopica fruit, Carica papaya seed and Spondias mombin stem bark mixed together in ratio 1:1:1:1
 Study Design: Extract of medicinal plants was assayed using glucose and streptozotocin-induced herperglycaemic rats model.
 Place and Duration of Study: Department of Pharmacognosy, Obafemi Awolowo University, IleIfe, Nigeria, between May, 2019 and January, 2022.
 Methodology: The extract of the combined plant parts was tested for toxicity in rats while its effects on glucose level, blood and biochemical components were also assessed. Its in-vitro anti-hyperglycaemic activity was assayed in α-amylase and α-glucosidase inhibitory models while its in-vivo effects were tested in glucose and streptozotocin-induced hyperglycaemic rats. The antioxidant activity of the extract was also carried out.
 Results: The extract did not show any adverse effects on blood sugar levels, haematological and biochemical parameters in normal rats in sub acute toxicity tests. The extract gave comparable (p > 0.05) α-amylase and α-glucosidase inhibitory effects to acarbose. In glucose-induced hyperglycaemic rats, its 100 mg/kg was the most effective dose with 19, 40, 43, and 57% activity that was significantly higher (p < 0.05) than the 10, 18, 24, and 40% activity given by glibenclamide (5 mg/kg) at the same time points. In streptozotocin-induced diabetic assay, its 50 mg/kg showed 31, 85, 85 and 82 % effects on days 4, 7, 10 and 14, respectively that was significantly higher than its 100 mg/kg and glibenclamide on days 7 and 10. The extract also elicited high free radical scavenging effects in all the antioxidant assays.
 Conclusion: The extract of the combination of four Nigerian antidiabetic plants mixed together in equal ratio gave significantly better antidiabetic activity at low doses than the individual plants without toxic effects.

Influences of Glimepiride Self-Nanoemulsifying Drug Delivery System Loaded Liquisolid Tablets on the Hypoglycemic Activity and Pancreatic Histopathological Changes in Streptozotocin-Induced Hyperglycemic Rats.

The development of an oral anti-diabetic medication characterized by enhanced hypoglycemic activity is in high demand. The goal was to study the hypoglycemic activity and pancreatic histopathology after the black-seed-based self-nanoemulsifying drug delivery system (SNEDDS) loaded with glimepiride liquisolid tablets to diabetic rats. The solubility of glimepiride in various vehicles was investigated. An optimization SNEDDS formulation was developed using a mixture of the experimental design approach. Box-Behnken design (BBD) was used to develop glimepiride liquisolid tablets utilizing Avicel PH 101 and Neusilin as a carrier mixture and FujiSil as a coating material. The quality attributes of the prepared tablets were assessed. Following the administration of the optimized tablets to diabetic rats, the pharmacodynamics and histopathological changes were investigated and compared to a commercial drug product. Results revealed that the optimized SNEDDS formulation that contains 15.43% w/w black seed oil, 40% w/w Tween 80, and 44.57% w/w Polyethylene glycol 400 showed an average droplet size of 34.64 ± 2.01 nm and a drug load of 36.67 ± 3.13 mg/mL. The optimized tablet formulation contained 0.31% Avicel in the carrier mixture, a 14.99 excipient ratio, and 8% superdisintegrant. Pre- and post-compression properties were satisfactory, and the optimized glimepiride liquisolid tablet showed a two-fold increase in dissolution. The optimized tablet demonstrated superior pharmacodynamics. The pancreatic tissues of the group treated with the optimized tablet displayed normal histological structure. The obtained data offered a commercially viable alternative for manufacturing solid dosage forms containing water-insoluble drugs, but additional clinical research is required.

Studies on Hypoglycaemic activity of the different extracts of Solanum torvum root

The objective of the study was to Studies on the hypoglycaemic activity of the different extracts of Solanum torvum (Solanaceae) root extracts on Wister albino rats. Solanum torvum roots were shade dried, powdered, and extracted by the Soxhlet extraction procedure using petroleum ether, chloroform, ethanol, and water. Swiss albino mice were chosen for the acute toxicity studies and follow the OECD guidelines 423. The hypoglycemic activity on adult Wistar albino rats at dose levels of 100, 200, and 400mg/kg p.o. respectively each using normoglycaemic, glucose loaded, and streptozotocin-induced hyperglycaemic rats. For activity comparison standard drug Metformin (150mg/kg) was used. Promising results were produced by the ethanol extract among all the tested extracts that are comparable to the reference standard metformin. The study entrenched the scientific foundation of the benefits of this plant in the medication of diabetes and asserts the use of the root of the plant for treating diabetes as demonstrate in folklore remedies.

Ethanol extract of the mushroom Coprinus comatus exhibits antidiabetic and antioxidant activities in streptozotocin-induced diabetic rats

Context Edible mushrooms have a long history of use in traditional Chinese or Japanese medicine. Coprinus comatus (O.F. Müll.) Pers. (Agaricaceae) contains antioxidant and antidiabetic agents. Objective To identify the benefits of ethanol extracts of the C. comatus fruit body in streptozotocin-induced hyperglycaemic rats by evaluating their blood glucose, glycosylated haemoglobin (HbA1c), insulin, glucagon-like peptide-1 (GLP-1), dipeptidyl peptidase-4 (DPP-4), and glutathione (GSH) levels, with and without extract administration. Materials and methods Wistar rats were either left untreated or were administered 45 mg/kg body weight (BW) streptozotocin; 45 mg/kg BW metformin; or 250, 500, or 750 mg/kg BW extract for 14 days. The blood glucose, GLP-1, DPP-4, GSH, insulin, and HbA1c levels were determined. Data were analysed using analysis of variance and Duncan’s multiple range tests. Results Preliminary data showed that administration of C. comatus ethanol extract dose of 250, 500, and 750 mg orally has no toxicity effects after 24 h administration. The ethanolic extract of fruiting body of C. comatus considerably reduced the rat’s fasting blood glucose levels 26.69%, and DPP-4 6.97% at dose of 750 mg. The extract reduced HbA1c 4–4.30%, increased GLP-1 71.09%, GSH 11.19% at dose of 500 mg, and increased insulin levels 13.83%. Extracts contain bioactive compounds such as flavonoid, alkaloid, terpenoids, vitamins C and E, rutin, and saponin. Conclusions The C. comatus extract can be used as herbal medicine that reduces diabetic symptoms. Further investigation on C. comatus extracts should be conducted with gas chromatography-mass spectrometry to characterise the bioactive compounds.

Effect of Bis(maltolato)oxovanadium(IV) on Zinc, Copper, and Manganese Homeostasis and DMT1 mRNA Expression in Streptozotocin-Induced Hyperglycemic Rats.

Simple SummaryDiabetes mellitus is a disease that affects some metabolic processes, altering the metabolism of trace elements associated with the antioxidant defense system. The insulin-mimetic activity of vanadium has received attention in recent years. However, the use of vanadium as an antidiabetic agent is limited due to its pro-oxidant properties, which are probably caused by interactions with other trace elements. There is currently little information on the interactions between vanadium and zinc, copper and manganese in diabetic rats. For these reasons, the objective of this study was to examine whether diabetic rats treated with bis(maltolato)oxovanadium(IV) (BMOV(IV)) undergo alterations in zinc, copper and manganese homeostasis, and whether such changes are related to the gene expression of the divalent metal transporter 1 (DMT1). The results obtained from this study showed that the metabolism of Zn, Cu and, to a lesser extent, Mn is altered by diabetes and that BMOV(IV) administered to diabetic rats at a dose of 3 mg V/day reverted the alterations in zinc and copper homeostasis produced by diabetes. The effect of this supplementation was possibly mediated by a decrease in food intake and DMT1 gene expression.Our aim was to examine whether vanadium (IV) corrects alterations in zinc, copper and manganese homeostasis, observed in streptozotocin-induced hyperglycemic rats, and whether such changes are related to divalent metal transporter 1 (DMT1) mRNA expression, and antioxidant and proinflammatory parameters. Four groups of Wistar rats were examined: control; hyperglycemic (H); hyperglycemic treated with 1 mg V/day (HV); and hyperglycemic treated with 3 mg V/day (HVH). Vanadium was supplied in drinking water as bis(maltolato)oxovanadium(IV) for five weeks. Zinc, copper and manganese were measured in food, excreta, serum and tissues. DMT1 mRNA expression was quantified in the liver. Hyperglycemic rats showed increased Zn and Cu absorption and content in the liver, serum, kidneys and femurs; DMT1 expression also increased (p < 0.05 in all cases). HV rats showed no changes compared to H rats other than decreased DMT1 expression (p < 0.05). In the HVH group, decreased absorption and tissular content of studied elements (p < 0.05 in all cases) and DMT1 expression compared to H (p < 0.05) were observed. Liver zinc, copper and manganese content correlated positively with glutathione peroxidase activity and negatively with catalase activity (p < 0.05 in both cases). In conclusion, treatment with 3 mg V/d reverted the alterations in zinc and copper homeostasis caused by hyperglycemia, possibly facilitated by decreased DMT1 expression.

β-Sitosterol Glucoside-Loaded Nanosystem Ameliorates Insulin Resistance and Oxidative Stress in Streptozotocin-Induced Diabetic Rats.

β-Sitosterol glucoside (SG), isolated from Senecio petasitis (Family Asteraceae), was loaded in self-nanoemulsifying drug delivery systems (SEDDS) in a trial to enhance its solubility and biological effect. Various co-surfactants were tested to prepare a successful SEDDS. The selected SG-loaded SEDDS had a droplet size of 134 ± 15.2 nm with a homogenous distribution (polydispersity index 0.296 ± 0.02). It also demonstrated a significant augmentation of SG in vitro release by 4-fold compared to the free drug suspension. The in vivo insulin sensitivity and antidiabetic effect of the prepared SG-loaded SEDDS were further assessed in streptozotocin-induced hyperglycemic rats. The hypoglycemic effect of SG-loaded nanosystem was evidenced by decreased serum glucose and insulin by 63.22% and 53.11%, respectively. Homeostasis model assessment-insulin resistance (HOMA-IR) index demonstrated a significant reduction by 5.4-fold in the diabetic group treated by SG-loaded nanosystem and exhibited reduced glucagon level by 40.85%. In addition, treatment with SG-loaded nanosystem significantly decreased serum MDA (malondialdehyde) and increased catalase levels by 38.31% and 64.45%, respectively. Histopathological investigations also supported the protective effect of SG-loaded nanosystem on the pancreas. The promising ability of SG-loaded nanosystem to ameliorate insulin resistance, protect against oxidative stress, and restore pancreatic β-cell secretory function warrants its inclusion in further studies during diabetes progression.

The effect of snakehead fish extract on acute wound healing process in hyperglycemic rats

Introduction: Wound healing is an integrated response to tissue injury. A hyperglycemic state can lead to delayed wound healing process. Snakehead fish (Channa striata) is native freshwater fish of South East Asia that contains high protein, albumin, and several micronutrients. The aim of this study is to evaluate the efficacy of snakehead fish extract on acute wound healing process in streptozotocin-induced hyperglycemic rats.Methods: This study was an experimental trial on the hyperglycemic animal model. Thirty male Wistar streptozotocin-induced rats were divided into two groups which were then given snakehead fish extract (Pujimin Plus®) 81mg a day for 10 days after wound infliction in intervention group and carboxymethyl cellulose sodium (Na-CMC) in control group. On day 0, day 3, and day 10 after wound infliction, the histological changes (number of neutrophil and fibroblast, and vascular changes of the wounded tissues) of each group were analyzed. Assessments were also made on erythema and crust formation by the visual scores.Results: Our study showed a significant increase in the number of fibroblasts on day 3 in the snakehead fish extract group compared to control group (40.33 ± 10.13 vs. 24.60 ± 10.25, p =0.04). There were no significant differences in vasculature and neutrophil numbers. The results also showed snakehead fish extract could decrease mean erythema visual score on day 3 (3.24 ± 0.25 vs. 3.64 ± 0.35) and decreased crust formation on day 5 (3.36 ± 0.75 vs 3.44 ± 0.83).Conclusions: Snakehead fish extract has potential effect to accelerate the wound healing process by increasing fibroblast, decreasing erythema, and decreasing crust formation in streptozotocin-induced hyperglycemic rats.

Effects of Channa striata Extract on Albumin Serum and Neutrophil-to-Lymphocyte Ratio in Hyperglycemic Rats with Wound Injury: A Randomized Control Study

BACKGROUND: Patients with hyperglycemia often experience slow wound healing due to poor circulation. Extract from the striped snakehead fish Channa striata has anti-inflammatory properties and a high albumin level. It has been widely used to accelerate wound healing in a post-operative setting. AIM: This study evaluated the effect of the C. striata extract Pujimin Plus® on the albumin serum level and neutrophil-to-lymphocyte ratio (NLR) in hyperglycemic rats experiencing wound injury. METHODS: This randomized controlled experiment was performed in 30 streptozotocin-induced hyperglycemic adult male Wistar rats (Rattus norvegicus). The rats were intentionally wounded, and the albumin and NLR levels were evaluated regularly. Overall, 15 rats in the intervention group were given 81 mg/day C. striata extract, and 15 rats in the control group received sodium-carboxymethyl cellulose as a placebo for 10 days. RESULTS: After 10 days of intervention the albumin level in the intervention group was higher than that in the control group (2.66 ± 0.36 vs. 2.46 ± 0.13 g/dL, p &gt; 0.05); the intervention group also showed a lower neutrophil level (23.22% vs. 26.98%, p &gt; 0.05), a higher lymphocyte level (65.66% vs. 62.16%, p &gt; 0.05), and a lower NLR value (0.37 vs. 0.45, p &gt; 0.05). None of these results was statistically significant. CONCLUSION: There was a possible positive effect of C. striata extract on albumin serum level and NLR value following wound injury in hyperglycemic rats.

The prophylactic potential of Zingiber officinale flowers and leaves extract to mitigate hyperglycemia in Sprague Dawley rats

PurposeInnovative health-promoting approaches of the era have verified phytoceutics as one of the prime therapeutic tools to alleviate numerous health-related ailments. The purpose of this paper is to probe the nutraceutic potential of ginger flowers and leaves against hyperglycemia.Design/methodology/approachThe aqueous extracts of ginger flowers and leaves were observed on Sprague Dawley rats for 8 weeks. Two parallel studies were carried out based on dietary regimes: control and hyperglycemic diets. At the end of the experimental modus, the overnight fed rats were killed to determine the concentration of glucose and insulin in serum. The insulin resistance and insulin secretions were also calculated by formulae by considering fasting glucose and fasting insulin concentrations. Furthermore, the feed and drink intakes, body weight gain and hematological analysis were also carried out.FindingsIn streptozotocin-induced hyperglycemic rats, the ginger flowers extract depicted 5.62% reduction; however, ginger leaves extract reduced the glucose concentration up to 7.11% (p = 0.001). Similarly, ginger flowers extract uplifted the insulin concentration up to 3.07%, while, by ginger leaves extract, the insulin value increased to 4.11% (p = 0.002). For the insulin resistance, the ginger flower showed 5.32% decrease; however, the insulin resistance was reduced to 6.48% by ginger leaves (p = 0.014). Moreover, the insulin secretion increased to 18.9% by flower extract and 21.8% by ginger leave extract (p = 0.001). The feed intake and body weight gain increased momentously by the addition of ginger flowers and leaves; however, the drink intake and hematological analysis remained non-significant by the addition of ginger parts.Originality/valueConclusively, it was revealed that leaves have more hypoglycemic potential as compared to flowers.

Isolation and characterization of anti-diabetic compound from Clerodendrum infortunatum L. leaves

Clerodendrum infortunatum L. (CI) leaves are traditionally used in the treatment of diabetic patients. This study aimed to isolate and characterize bioactive compounds from CI leaves and evaluate their anti-diabetic activities (ADI). The CI leaves extracts ADI was estimated on streptozotocin-induced hyperglycemic rats by applying a different dose of extract and compared with the anti-diabetic medicine (Glibenclamide). The intraperitoneal's acute effect showed the progressive fall of the blood glucose level until 120 min on diabetic rats by applying the CI extract. Continuous administration of the target ethanolic extracts of CI at 0 to 28 days leads to a decrease in fasting serum glucose (FSG), total cholesterol (TG), and low-density lipoprotein (LDL) levels, while high-density lipoprotein (HDL) was increased. The ethanolic extract of CI produced five fractions, fraction-1 indicated a greater insulin secretion effect compared to other fractions. So, the structure of fraction-1 was elucidated and characterized by IR, 1H, 13C-NMR, COSY, and MS and the identified compound name is phaeophytin a. This study suggests that phaeophytin a exhibits significant anti-diabetic activity.

Anti-diabetic potential of Plectranthus lanuginosus in streptozotocin-induced diabetic rats

Purpose: To determine the antidiabetic effect of methanol extract of Plectranthus lanuginosus leaves in streptozotocin-induced hyperglycemic (HGD) rats.&#x0D; Methods: P. lanuginosus leaves were collected from Saad Medhas, Al Baha, Kingdom of Saudi Arabia. After defatting with n-hexane, they were extracted in vacuo at 40 oC with 75 % methanol. Streptozotocin (50 mgkg−1, i.p.) was used to induce hyperglycemia (diabetes) in the rats. The HGD rats received either standard drug (glibenclamide, 10 mgkg−1, p.o.) or Plectranthus lanuginosus leaf methanol leaf extract (PLLM) at doses of 200 and 400 mgkg−1/day, p.o. for 21 consecutive days. Blood samples were taken from the rat tails 2 h after dosing, and at 7-day intervals (i.e., 0, 7th, 14th and 21st days). The blood samples were used for measurement of fasting blood glucose (FBS), using a glucometer. On the 21st day, the rats were sacrificed via cardiac puncture. The activities of liver marker enzymes (SGPT and SGOT), and serum lipid profile (cholesterol, triglycerides, HDL and LDL) were determined using a hemolyzer.&#x0D; Results: Streptozotocin treatment produced significant hyperglycemia in the rats (348.9 ± 5.6) when compared to control (79.2 ± 1.3). However, PLLM (200 and 400 mg kg−1) produced significant and dose-dependent anti-diabetic (166.4 ± 5.6 and 123.86 ± 6.8 respectively) and antihyperlipidemic effects in HGD rats, at levels similar to those produced by the standard drug, glibenclamide (120.6 ± 6.4).&#x0D; Conclusion: P. lanuginosus leaf extract possesses pronounced anti-diabetic and anti-hyperlipidemic properties which may be due to the presence of phenolic and flavonoid constituents in the plant. Therefore, the plant extract can be further developed for the management of diabetes

Chemical Profile of Launaea nudicaulis Ethanolic Extract and Its Antidiabetic Effect in Streptozotocin-Induced Rats.

Launaea nudicaulis is used in folk medicine worldwide to treat several diseases. The present study aimed to assess the antidiabetic activity of L. nudicaulis ethanolic extract and its effect on diabetic complications in streptozotocin-induced hyperglycemic rats. The extract was orally administrated at 250 and 500 mg/kg/day for 5-weeks and compared to glibenclamide as a reference drug at a dose of 5 mg/kg/day. Administration of the extract exhibited a potential hypoglycemic effect manifested by a significant depletion of serum blood glucose concurrent with a significant elevation in serum insulin secretion. After 5-weeks, extract at 250 and 500 mg/kg/day decreased blood glucose levels by about 53.8 and 68.1%, respectively, compared to the initial values (p ≤ 0.05). The extract at the two dosages prevented weight loss of rats from the 2nd week till the end of the experiment, compared to diabetic control rats. The extract further exhibited marked improvement in diabetic complications including liver, kidney and testis performance, oxidative stress, and relative weight of vital organs, with respect to diabetic control. Histopathological examinations confirmed the previous biochemical analysis, where the extract showed a protective effect on the pancreas, liver, kidney, and testis that degenerated in diabetic control rats. To characterize extract composition, UPLC-ESI–qTOF-MS identified 85 chromatographic peaks belonging to flavonoids, phenolics, acyl glycerols, nitrogenous compounds, and fatty acids, with four novel phenolics reported. The potential anti-diabetic effect warrants its inclusion in further studies and or isolation of the main bioactive agent(s).

The Anti-nociceptive Effect of Ellagic Acid in Streptozotocin-induced Hyperglycemic Rats by Oxidative Stress Involvement.

Introduction:Hyperalgesia is among the current complications of diabetes mellitus; oxidative stress and inflammation were influential in its development. As an herbal component, Ellagic Acid (EA) has some biological activities, including antioxidant and anti-inflammatory effects. This study was designed to evaluate the possible beneficial effect of EA on hypernociception in Streptozotocin (STZ)-induced hyperglycemic rats.Methods:Forty-eight male Wistar rats were divided into the control (receiving vehicle), hyperglycemic, EA (25 mg/kg)-treated control, EA (50 mg/kg)-treated control, EA (25 mg/kg)-treated hyperglycemic, and EA (50 mg/kg)-treated hyperglycemic groups. Hyperglycemia was induced by a single Intraperitoneal (IP) injection of STZ (60 mg/Kg). EA was administered daily by oral gavage for four weeks. The nociceptive response was assessed using Tail-Flick (TF) and Hot-Plate (HP) tests. Also, oxidative stress markers, including Malondialdehyde (MDA), Total Oxidant Status (TOS), and Total Antioxidant Capacity (TAC) in the serum, were evaluated.Results:Hyperglycemic animals were found with significant changes, including a reduction in TF and HP latencies, an elevation in serum MDA level and TOS, and a decrease in serum TAC compared with controls. The treatment of hyperglycemic rats with EA facilitated the reduction of TF latency at the dose of 25 mg/kg and HP latency at 50 mg/kg. Furthermore, EA significantly increased TAC and decreased MDA level at a 50 mg/kg dose and reduced TOS at both doses in the serum of hyperglycemic animals. No significant alterations were found in the parameters studied in EA-treated normal rats.Conclusion:These results displayed the antinociceptive effect of EA in hyperglycemic rats via attenuating oxidative stress. Therefore, EA appears to be a promising agent for managing. Hyperglycemic hypernociception.HighlightsHyperalgesia is among the current complications of diabetes mellitus.Oxidative stress and inflammation were influential in its development.EA has some biological activities, including antioxidant and anti-inflammatory effects.Plain Language SummaryDN is among the most common chronic complications of diabetes among diabetic patients. DPN is mainly characterized by pain perception alterations, increased sensitivity to mild painful stimuli (hyperalgesia), and abnormal pain sensitivity to stimuli. On the other hand, hyperglycemia by induction of multiple changes, such as fatty acid metabolism abnormalities plays a crucial role in developing DN. Oxidative stress and inflammation are involved in the pathogenesis of DPN. The lack of efficacy and various adverse effects of the current medications for DNP, therefore, new therapeutic candidates are continuously required to improve DNP. Several studies reported the antinociceptive activity of EA in different animal models of pain, such as formalin. Since oxidative stress is involved in diabetic hyperalgesia, compounds with antioxidant properties are good candidates for DN management. Therefore, this research aimed to determine the possible effectiveness of EA and evaluate some oxidative stress-related mechanisms.

Effects of Rutin on Wound Healing in Hyperglycemic Rats.

Long-term poor glycemic control negatively affects macrovascular and microvascular diseases, as well as wound restoration. Buckwheat is a good source of rutin (quercetin-3-O-rutoside) and has benefits in regulating blood sugar. This study was to evaluate the antioxidant and anti-inflammatory effects of rutin on wound healing in streptozotocin-induced hyperglycemic rats. Eighteen male Wistar rats were randomly divided into three groups: normal (NDM), hyperglycemic (DM), and hyperglycemic with rutin (DMR). After induction of hyperglycemia for 2 days, a 15 × 15 mm wound was induced on the back of each rat. Intraperitoneal injection of rutin significantly ameliorated diabetes-induced body weight loss and improved metabolic dysfunctions of hyperglycemic rats. Based on appearance and histopathological staining, rutin promotes wound healing and inhibits production of inflammatory cells. The immunoblotting data indicated that rutin promotes production of antioxidant enzymes induced by nuclear factor erythroid 2-related factor 2 (NRF2), inhibits the expression of matrix metalloproteinases (MMPs) regulated by NF-κB, and decreases the expression of vascular endothelial growth factor (VEGF). It also promotes the expression of neurogenic-related protein (UCH-L1). The aforementioned results indicated that rutin reduces oxidative stress and inflammatory response in hyperglycemic rats, promoting wound healing and subsequently reducing the risk of wound ulcers.

Antihyperglycaemic activity of ethylacetate extract of Chlorophytum alismifolium in type 2 diabetes: The involvement of peroxisome proliferator-activated receptor-γ and dipeptidyl peptidase-4

ObjectiveThis research is to investigate the antihyperglycaemic activity and the underlying mechanisms of action of the ethylacetate extract of Chlorophytum alismifolium (EACA) tubers in a type 2 diabetes model. MethodsThe tubers were processed and sequentially extracted in hexane followed by ethylacetate, using a Soxhlet apparatus, and subjected to gas chromatography-mass spectrometry (GC–MS). The acute toxicity of EACA was investigated in albino Wistar rats. An antihyperglycaemic study was carried out using high-fat diet (pelletized diet and margarine in the ratio of 10:1 and 20% fructose solution) and streptozotocin-induced hyperglycaemic Wistar rats. The effects of the extract (150, 300 and 600 mg/kg) on blood glucose level, insulin, peroxisome proliferator-activated receptor-γ (PPAR-γ) and dipeptidyl peptidase-4 (DPP-4) were evaluated using enzyme-linked immunosorbent assay. ResultsThe oral median lethal dose in Wistar rats was estimated to be > 5000 mg/kg. Treatment with EACA at all doses significantly reduced the fasting blood glucose levels, compared to the hyperglycaemic control, and over time. Administration of EACA increased the serum insulin and PPAR-γ levels while decreasing DPP-4 levels. GC–MS analysis revealed the presence of 13 compounds, with isothiazole and isoxazolidine covering total area of 24.6% and 22.69%, respectively. ConclusionThe findings from this study showed that EACA has important compounds with beneficial effect in type 2 diabetes and acts by increasing insulin secretion and PPAR-γ level and decreasing DPP-4 activity.