Potential In Diabetic Rats Research Articles

Extraction, HPTLC Analysis and Antiobesity Activity of Jatropha tanjorensis and Fraxinus micrantha on High-Fat Diet Model in Rats.

The accumulation of body fat due to an imbalance between calorie intake and energy expenditure is called obesity. Metabolic syndrome increases the risk of heart disease, type 2 diabetes, and stroke. The purpose of this study was to determine the effect of Jatropha tanjorensis (J.T.) and Fraxinus micrantha (F.M.) leaf extracts on high-fat diet-induced obesity in rats. Normal control, high-fat diet (HFD) control, orlistat standard, and test groups were created using male Albino Wistar rats (n = 6 per group) weighing 190 ± 15 g. Except for the control group, all regimens were administered orally and continued for 6 weeks while on HFD. Evaluation criteria included body weight, food intake, blood glucose, lipid profile, oxidative stress, and liver histology. High-Performance Thin Layer Chromatography (HPTLC) analysis was performed using a solvent system (7:3 hexane: ethyl acetate for sitosterol solution and Jatropha tanjorensis extracts and 6:4 hexane: ethyl acetate: 1 drop of acetic acid for esculetin and Fraxinus micrantha extracts). There were no deaths during the 14 days before the acute toxicity test, indicating that aqueous and ethanolic extracts of both J.T. and F.M. did not produce acute toxicity at any dose (5, 50, 300, and 2000 mg/kg). The ethanolic and aqueous extracts of J.T. and F.M. leaves at 200 and 400 mg/kg/orally showed a reduction in weight gain, feed intake, and significant decreases in serum glucose and lipid profile. As compared to inducer HFD animals, co-treatment of aqueous and ethanolic extract of both J.T. and F.M. and orlistat increased the levels of antioxidant enzymes and decreased lipid peroxidation. The liver's histological findings showed that the sample had some degree of protection. These results indicate that ethanolic samples of J.T. have antidiabetic potential in diabetic rats fed an HFD. The strong antioxidant potential and restoration of serum lipid levels may be related to this. Co-treatment of samples JTE, JTAQ, FME, FMAQ and orlistat resulted in an increase in antioxidant enzymes and reduction in lipid peroxidation as compared to inducer HFD animals. We report, for the first time, on using these leaves to combat obesity.

Pomegranate peel extract protects against the development of diabetic cardiomyopathy in rats by inhibiting pyroptosis and downregulating LncRNA-MALAT1.

Background: Pyroptosis is an inflammatory programmed cell death accompanied by activation of inflammasomes and maturation of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18. Pyroptosis is closely linked to the development of diabetic cardiomyopathy (DC). Pomegranate peel extract (PPE) exhibits a cardioprotective effect due to its antioxidant and anti-inflammatory properties. This study aimed to investigate the underlying mechanisms of the protective effect of PPE on the myocardium in a rat model of DC and determine the underlying molecular mechanism. Methods: Type 1 diabetes (T1DM) was induced in rats by intraperitoneal injection of streptozotocin. The rats in the treated groups received (150mg/kg) PPE orally and daily for 8weeks. The effects on the survival rate, lipid profile, serum cardiac troponin-1, lipid peroxidation, and tissue fibrosis were assessed. Additionally, the expression of pyroptosis-related genes (NLRP3 and caspase-1) and lncRNA-MALAT1 in the heart tissue was determined. The PPE was analyzed using UPLC-MS/MS and NMR for characterizing the phytochemical content. Results: Prophylactic treatment with PPE significantly ameliorated cardiac hypertrophy in the diabetic rats and increased the survival rate. Moreover, prophylactic treatment with PPE in the diabetic rats significantly improved the lipid profile, decreased serum cardiac troponin-1, and decreased lipid peroxidation in the myocardial tissue. Histopathological examination of the cardiac tissues showed a marked reduction in fibrosis (decrease in collagen volume and number of TGF-β-positive cells) and preservation of normal myocardial structures in the diabetic rats treated with PPE. There was a significant decrease in the expression of pyroptosis-related genes (NLRP3 and caspase-1) and lncRNA-MALAT1 in the heart tissue of the diabetic rats treated with PPE. In addition, the concentration of IL-1β and caspase-1 significantly decreased in the heart tissue of the same group. The protective effect of PPE on diabetic cardiomyopathy could be due to the inhibition of pyroptosis and downregulation of lncRNA-MALAT1. The phytochemical analysis of the PPE indicated that the major compounds were hexahydroxydiphenic acid glucoside, caffeoylquinic acid, gluconic acid, citric acid, gallic acid, and punicalagin. Conclusion: PPE exhibited a cardioprotective potential in diabetic rats due to its unique antioxidant, anti-inflammatory, and antifibrotic properties and its ability to improve the lipid profile. The protective effect of PPE on DC could be due to the inhibition of the NLRP3/caspase-1/IL-1β signaling pathway and downregulation of lncRNA-MALAT1. PPE could be a promising therapy to protect against the development of DC, but further clinical studies are recommended.

Cassia occidentalis Potentiates wound Healing Process in Type-2 Diabetic Rats

Indian Journal of Natural Products,2022,36,1,52-57.DOI:10.5530/ijnp.2022.1.8Published:February 2023Type:Original ArticleAuthors:Rajesh Singh Pawar, Avinash Singh Mandloi, Umesh Kumar Patil, and Shweta Kumar Author(s) affiliations:Rajesh Singh Pawar1,2,*, Avinash Singh Mandloi1, Umesh Kumar Patil3, Shweta Kumar4 1Pharmacognosy and Phytochemistry Laboratory, Faculty of Pharmacy, VNS Group of Institutions, Bhopal, Madhya Pradesh, INDIA. 2Department of Pharmacy, Truba Institute of Pharmacy, Bhopal, Madhya Pradesh, INDIA. 3Department of Pharmacognosy, Department of Pharmaceutical sciences, Dr. Harisingh Gour Vishwavidyalaya (A Central University), Sagar, Madhya Pradesh, INDIA. 4Department of General Medicine, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, INDIA. Abstract:Introduction: This work is focus on a cost-effective herbal hydrogel formulation comprising of extract, from the leaves of Cassia occidentalis L. (Caesalpiniaceae). The formulation is highly effective for delayed wound healing due to diabetes. Background: Cassia occidentalis (CO) is extensively used in folklore medicine system. It is a common weed scattered from foothills of Himalayas to West Bengal, South India, Burma and Srilanka. Objectives: The study aimed to explore the role of Cassia occidentalis (leaf) for wound healing potential in diabetic rats using the excision wound model. Materials and Methods: The characterization of the phytoconstituents and bioavailability profiles of methanolic extract of CO (MCO) were investigated using High-Performance Liquid Chromatography-Photodiode Array Detector analysis. Insulin resistance was induced in rats by feeding them a diet rich in fructose and hyperglycemia was induced by injecting streptozotocin (STZ) at a dose of 40 mg/kg body weight (bw), intraperitoneally (ip). After confirmation of diabetes fasting blood glucose level, the wound was induced. Excision wound healing activity was examined on Wistar rats. Results: The hydrogel of MCO (5 and 10%) reduced significantly wound size. Significant mean epithelialization period, higher hydroxyproline content and tensile strength were revealed at the concentrations of MCO hydrogel of 5 and 10% compared to the diabetic wound control group. Conclusion: These results provide promising baseline information for the wound healing potential of MCO in type-2 diabetes treatment. Keywords:Biochemical parameters, Cassia occidentalis, Hydrogel, Hydroxyproline, HyperglycemiaView:PDF (906.38 KB)

Oral Administration of Lactobacillus casei and Bifidobacterium bifidum Improves Glucagon like Peptide-1(GLP-1) and Glucose-Dependent Insulinotropic Polypeptide (GIP) Level in Streptozotocin Induced Diabetic Rats

The gut microbiome plays significant role in the function and integrity of the gastrointestinal tract. They also maintain immune homeostasis and host energy metabolism. The metabolic products of these intestinal microbes can alter carbohydrate metabolism, nutrient absorption and reduce appetite to promote healthy lifestyle. Intestinal disbiosis observed in metabolic disorders like obesity and diabetes. Restoration of dysbiosed gut microbiome through oral administration of probiotics that may have profound health effect in diabetes. In case of diabetes, reports postulated impaired level of incretin, therefore we explored the effect of oral administration of probiotic bacteria Lactobacillus casei NCDC 017 (LC017) and Bifidobacterium bifidum NCDC 231 (BB231) alone and in combination on secretion of incretin hormones such as glucagon like peptide-1 and glucose dependent insulinotropic polypeptide. Thirty six male Wistar rats were randomly divided into six groups and diabetes was induced by single dose of streptozotocin (50 mg/kg body weight) in experimental rats intraperitonially except a group of healthy rats. The diabetic rats were daily administered orally with single dose (~107cfu/ml) of LC017 and BB231 alone and in combination for 28 days. Also, one group of diabetic rats was treated with an anti-diabetic drug, acarbose (10mg/kg body weight) and used a standard control. The change in body weight, sucrose tolerance test, GLP-1, GIP level in serum and GLP-1 level in different part of intestine were observed. The results have shown reduction in body weight in diabetic rats as compared to non-diabetic rats but improved after treatment of probiotic bacteria. Administration of LC017 and BB231 significantly improved GLP-1 and GIP level which were initially impaired in diabetic rats and their combination significantly decreased glucose level in sucrose tolerance test. This study indicated that LC017 and BB231 have significant hypoglycaemic potential in diabetic rats by increasing GLP-1 and GIP level. These findings offered a base for the use of LC017 and BB231 for improvement and treatment of diabetes.

Phytotherapeutic potential of bi-herbal extract of cinnamon and turmeric: in vivo antidiabetic studies

BackgroundThe spices, cinnamon and turmeric have both culinary and pharmaceutical applications. Earlier studies proved their effect on reducing the symptoms associated with type 2 diabetes, a major lifestyle disease affecting millions world over. In our work, we prepared a bi-herbal extract of cinnamon and turmeric and studied its effect to alleviate the symptoms of type 2 diabetes in rat model.MethodThe phenolic rich bi-herbal extract was given to diabetes induced male wistar rats for 28 days at two different concentrations (50 and 150 mg/Kg bwt.). The changes in blood glucose level were monitored at weekly interval. At the end of the experiment, blood serum was collected and used for the estimation of lipid profile, Glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), Total Protein (TP), Albumin, Urea and Creatinine levels.ResultThe serum analysis revealed that administration of the bi-herbal extract at 150 mg/Kg bwt. significantly reduced the blood glucose level (152.60 ± 40.2 mg/dL; p < 0.05) of diabetic animals as compared to diabetic control (335.40 ± 67.3 mg/dL; p < 0.05) at the end of 4 weeks. The treatment also resulted in the reduction of total cholesterol and LDL-cholestrol levels as compared to diabetic control animals. The histopathological examination of tissues showed the improvement in pancreatic architecture and restoration of tissue integrity in liver and kidney.ConclusionThe study concludes that methanol extract of combination of cinnamon and turmeric has good hypoglycemic, hypolipidemic and organ protective potential in diabetic rats which could be developed into functional food supplementation for the prevention of type 2 diabetes.

Hypoglycemic and hypolipidemic effects of two mangrove plants in a streptozotocin-induced animal model of diabetes.

Objective:This study aims at evaluating the anti-diabetic, hypolipidemic, and pancreatic histopathological changes of Rhizophora mucronata and Avicennia marina.Materials and Methods:The experimental rats were divided into eight groups (n = 15 each). Streptozotocin was used to induce diabetes. Daily oral administration of an aqueous extract from the leaves of R. mucronata and A. marina at 400 mg/kg BW, and a mixture of the two extracts for 6 weeks was assessed. The measurements of serum glucose, insulin, and lipid profile were carried out. Pancreatic specimens were collected from all groups and processed for pathological studies.Results:The study revealed that the plant extracts restored the levels of diabetic markers and lipid profiles of diabetic rats, with no significant changes in non-diabetic ones. The extract of R. mucronata exhibited more promising anti-diabetic and hypolipidemic effects than A. marina singly or combined.Conclusion:Leaf extracts from R. mucronata, singly or combined, and A. marina, induced a potent anti-diabetic and hypolipidemic potential in diabetic rats.

Hypoglycaemic, insulin releasing, and hepatoprotective effect of the aqueous extract of Aloe perryi Baker resin (Socotran Aloe) in streptozotocin-induced diabetic rats

ABSTRACT This study evaluated the anti-diabetic and hepatic protective effect of the aqueous extract of the Aloe perryi (AP) in streptozotocin-induced diabetic rats. Rat were divided into control, diabetic, diabetic + glimepiride, diabetic + AP (150 or 300 mg/Kg) groups. AP (300 mg/Kg) alone lowered fasting serum glucose levels but increased insulin levels and HOMA-β. At both doses, AP significantly decreased hepatic levels of CHOL and LDL-C and reduced serum levels of TGs, CHOL, and LDL-C, without altering levels of HDL-C in the diabetic rats. Also, they improved liver architectures and reduced serum levels of ALT and AST. Concomitantly, they suppressed hepatic levels of MDA, and increase hepatic levels of SOD, GSH, CAT, and GPx. Except for lipids, the effect of the extract on all other parameters was more profound with the higher dose of the extract. In conclusion, AP extract exerts hypoglycaemic, insulin-releasing, and hepatic antioxidant potentials in diabetic rats.

Antidiabetic activity of Carallia brachiata Lour. leaves hydro-alcoholic extract (HAE) with antioxidant potential in diabetic rats

Ethnomedicinal surveys have documented the traditional use of Carallia brachiata (Lour.) Merill (Rhizophoraceae) leaves in the management of diabetes mellitus in the Northeastern region of India. This study screens the hydro-alcoholic extract (HAE) of C. brachiata leaves for antioxidant and antidiabetic activities. The HAE was prepared using ethanol:water (7:3) by cold maceration method. The antidiabetic activity of HAE was evaluated in vivo in streptozotocin-induced diabetic rats at the doses of 250 or 500 mg/kg body weight for 21 days. The extract was also evaluated for in vitro and in vivo antioxidant activity. Results revealed that HAE of C. brachiata leaves possesses good hypoglycemic activity in diabetic rats. The hypoglycemic activity of HAE was found significant as compared to normal rats. Results of antioxidant activity were found statistically significant compared to standard drugs, quercetin and gallic acid. Results indicated a possible role of the HAE of C. brachiata leaves as herbal antioxidants in the prevention and/ or treatment of oxidative stress-induced diabetes. Results suggested that antioxidant plant phenolics/ flavonoids might be responsible for the antidiabetic efficacy of HAE. Further research can be undertaken on the HAE of C. brachiata leaves for exploration of biochemical mechanisms of antidiabetic action with the isolation of bioactive flavonoids having antidiabetic potential.

β-cell Regenerative Potential of Selected Herbal Extracts in Alloxan Induced Diabetic Rats.

Effective β-cell regeneration is a recognized therapeutic strategy in the treatment of type 1 diabetes mellitus. Regeneration of β-cells could be achieved via exogenous natural sources as medicinal plant extracts. Medicinal plants selected for the investigation were Spondias pinnata (Linn. f.) Kurz, Coccinia grandis (L.) Voigt and Gmelina arborea Roxb. The objective was to determine the β-cell regenerative potential of these plant extracts in alloxan-induced diabetic rats. Alloxan monohydrate was used to induce diabetes (150 mg/kg, ip). Wistar albino rats were divided into six groups (n=6); healthy untreated rats (healthy control), alloxan-induced diabetic untreated rats (diabetic control), diabetic rats received the extracts (treatment groups) of S. pinnata (1.0 g/kg), C. grandis (0.75 g/kg), G. arobrea (1.00 g/kg) and diabetic rats received glibenclamide (0.5 mg/kg; positive control). The above treatment was continued for 30 days. On the 30th day, the rats were sacrificed and biochemical parameters were determined. In addition, histopathology and immunohistochemistry on the pancreatic tissue were done on the 30th day. According to the results obtained for biochemical parameters, there was a significant increase in the concentrations of serum insulin and C-peptide in plant extracts treated diabetic rats (p < 0.05). The extract of C. grandis produced the highest degree of β-cell regeneration demonstrated through an increase in the number of islets and percentage of the insulin-secreting β-cells (75%) in the pancreas of diabetic rats (p < 0.05) based on the histopathology and immunohistochemistry findings. The results revealed that the selected extracts of C. grandis (0.75 g/kg), G. arborea (1.00 g/kg) and S. pinnata (1.00 g/kg) exerted β-cell regenerative potential in diabetic rats. The three plant extracts would be valued as natural agents of prompting the β-cell regeneration in vivo.

AYURVEDIC POLYHERBAL FORMULATION AND DIABETES AN OVERVIEW

At this era the world is suffering from many health dilemmas. Most of them are environmental, ecological, depending on several human races or ethnic background. Diabetes is one of them. Diabetes is chronic metabolic disorder which is group of diverse complications. The present study is overview of various 30 Ayurvedic polyherbal formulations and their significance as antidiabetic potential in diabetic rats. Models used are alloxon induced, streptozotocin induced and streptozotocin-nicotinamide induced diabetes. Plants have always been an exemplary source of drugs and many of the currently available drugs have been derived directly or indirectly from them. The Ayurveda and other Indian literature strongly believe; current scientific evidences, the use of medicinal plants in treatment of various human diseases is found significant. Diverse researches conducted in the last few decades on plants, mentioned in ancient literature or used traditionally for diabetes, have shown antidiabetic property. Further research should continue, especially in areas within nations that have received less attention.

Antidiabetic activity of hydro-alcoholic stem bark extract of Callicarpa arborea Roxb. with antioxidant potential in diabetic rats

BackgroundDespite the availability of synthetic antidiabetic drugs, diabetes mellitus is still affecting millions of people with increasing rate of disease incidence and mortality throughout the world. Ethnomedicinal survey documents the traditional usefulness of Callicarpa arborea Roxb. stem bark in the management of diabetes mellitus. Materials and methodsIn our study, hydro-alcoholic extract (HAE) of Callicarpa arborea stem bark was prepared according to WHO guidelines for herbal drugs, and screened for antidiabetic activity in streptozotocin (STZ)-induced diabetic rats. Acute oral toxicity and in vitro antioxidant activity studies along with phytochemical analyses of HAE were also carried out. ResultsAcute oral toxicity study indicated that HAE was safe up to a dose of 2000mg/kg body weight of rats. Results of antidiabetic activity study revealed that HAE of C. arborea stem bark possesses significant (p<0.05) hypoglycemic activity compared to normal control group in experimental rats. Histological observations of treated pancreas and liver tissues confirmed the antidiabetic efficacy of HAE. In antioxidant activity, HAE exhibited significant radical scavenging activity. ConclusionFrom results, it can be concluded that HAE of C. arborea stem bark may have possible role as herbal antioxidants in the prevention and/or treatment of oxidative stress-induced diabetes mellitus. The antioxidant property of plant phenolic and flavonoid contents present in HAE might be responsible for the antidiabetic efficacy of C. arborea stem bark.

GLUCOSE HOMEOSTATIC AND PANCREAS PROTECTIVE POTENTIAL OF TECOMELLA UNDULATA ROOT EXTRACT IN STREPTOZOTOCIN INDUCED DIABETIC RATS .

Objective: The study was aimed to evaluate glucose homeostatic and pancreas protective potential of Tecomella undulata root extract in streptozotocin induced diabetic rats.Methods: The ethanolic root extract was prepared by following standard soxhlation methods. The experimental design was divided in to control and treated groups for 28 days of comparative experimental schedule. The body and organ weights, serum biochemistry, histo-pathology, hematology and toxicity profiles were assayed by following standard methods and protocols.Results: The treatment of ethanolic extract of root of T. undulata was significantly (p ≤ 0.001) reduced glucose levels at 7day, 14day, 21day and 28 days in comparison to standard drug of metformin. Correspondingly, lipid profile i.e. total cholesterol, HDL, VLDL, LDL and triglyceride were also altered significantly. Whereas, body and organs weight and hematological parameters were not shown significant changes. Subsequently, toxicity profile i.e. hepatic and renal parameters were remained under normal ranges. Corresponding, the treatment of ethanolic root extract caused normalcy of histoarchitecture of pancreas in comparison to standard drugs.Conclusion: The results of study illustrated that Tecomella undulata root extract possessing particular kind of phytocompounds which caused glucose homeostatic and pancreas protective potential in diabetic rats.

Lectins from seeds of Abrus precatorius: Evaluation of Antidiabetic and Antihyperlipidemic Potential in Diabetic Rats

There is an increasing patient demand to use natural products for diabetes treatment due to the side effects associated with the use of insulin and oral hypoglycemic agents. This work highlights the potential of Abrus precatorius seeds for their antidiabetic activity. The aim of this study was to evaluate the antidiabetic, antihyperlipidemic and in vivo toxicity of the lectins purified from the seeds of Abrus precatorius (Fabaceae), locally known as Gunja. The present work involves purification of lectins from the seeds of A. precatorius (ABA), followed by characterization. The in vivo acute toxicity study of ABA was carried out as per the OECD 425 guidelines. The antidiabetic potential was evaluated in alloxan monohydrate (AXN) induced diabetic rats at two dose levels (150 mg/kg and 200 mg/kg) body weight, daily for 14 days. Various parameters such as body weight, food consumption, serum glucose levels, serum cholesterol levels and liver glycogen levels were determined post ABA treatment. Acute toxicity study revealed ABA to be non-toxic even at a high dose of 2000 mg/kg body weight (bw). Increased body weight, food consumption and decreased serum glucose levels were observed in diabetic rats treated with the ABA compared to the diabetic control rats. Diabetic rats treated with the ABA showed altered lipid profiles and liver glycogen levels which were found to be reversed to near normal levels than the diabetic control rats. These findings highlight the efficacy of A. precatorius seed lectins as potential antidiabetic and anti hyperlipidemic agent that can be used as adjunct therapy for diabetes treatment.

Impact of antioxidants on seminal vesicles function and fertilizing potential in diabetic rats.

Diabetes mellitus significantly affects the male reproduction and sexual function. In the present study, we investigated the diabetes-induced dysfunction of seminal vesicles (SVs) in the diabetes-rat model and the role of antioxidants. Streptozotocin-induced diabetes after 4 weeks caused smaller size of the organs, hypercontractility, histological abnormalities, increased concentrations of malondialdehyde in the serum and tissue, overexpression of oxidative stress markers, and cleaved caspase-3 as identified by immunohistochemistry in the SVs. In addition, diabetes resulted in deceased levels of serum testosterone and no newborns after the mating studies. Antioxidants significantly normalized all the above parameters, except for the severely decreased serum testosterone levels and the negative outcome of the mating studies. The present study gives evidence for the important role of diabetes-induced oxidative stress in the function and structure of these androgen-dependent organs. Antioxidants may be a promising supplementary therapy for diabetic male patients to alleviate ejaculatory disorders but alone is not efficient treatment for the mitigation of infertility.

Effect of sodium tungstate on visual evoked potentials in diabetic rats

To evaluate the effect of sodium tungstate on visual evoked potentials (VEPs) in diabetic rats. Wistar rats were randomly divided into three groups as normal control, diabetic control and diabetic rats treated with sodium tungstate. Diabetes was induced by single intraperitoneal injection of streptozotocin (50 mg/kg). Sodium tungstate [40 mg/(kg·d)] was administered for 12wk and then VEPs were recorded. Additionally, thiobarbituric acid reactive substance (TBARS) levels were measured in brain tissues. The latencies of P1, N1, P2, N2 and P3 waves were significantly prolonged in diabetic rats compared with control group. Diabetes mellitus caused an increase in the lipid peroxidation process that was accompanied by changes in VEPs. However, prolonged latencies of VEPs for all components returned to control levels in sodium tungstate-treated group. The treatment of sodium tungstate significantly decreased brain TBARS levels and depleted the prolonged latencies of VEP components compared with diabetic control group. Sodium tungstate shows protective effects on visual pathway in diabetic rats, and it can be worthy of further study for potential use.

Antidiabetic activity of Artemisia amygdalina Decne in streptozotocin induced diabetic rats.

Artemisia species have been extensively used for the management of diabetes in folklore medicine. The current study was designed to investigate the antidiabetic and antihyperlipidemic effects of Artemisia amygdalina. Petroleum ether, ethyl acetate, methanol, and hydroethanolic extracts of Artemisia amygdalina were tested for their antidiabetic potentials in diabetic rats. The effect of extracts was observed by checking the biochemical, physiological, and histopathological parameters in diabetic rats. The hydroethanolic and methanolic extracts each at doses of 250 and 500 mg/kg b. w significantly reduced glucose levels in diabetic rats. The other biochemical parameters like cholesterol, triglycerides, low density lipoproteins (LDL), serum creatinine, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), and alkaline phosphatise (ALP), were found to be reduced by the hydroethanolic and methanolic extracts. The extracts also showed reduction in the feed and water consumption of diabetic rats when compared with the diabetic control. The histopathological results of treated groups showed the regenerative/protective effect on β-cells of pancreas in diabetic rats. The current study revealed the antidiabetic potential of Artemisia amygdalina being effective in hyperglycemia and that it can effectively protect against other metabolic aberrations caused by diabetes in rats, which seems to validate its therapeutic traditional use.

In Situ Low Coherence Enhanced Backscattering Spectroscopy (LEBS) for Risk-Stratification of Colon Carcinogenesis: Implications for Screening and Surveillance.

showed that the resting [Ca]i was increased in 6-wk streptozotocin (STZ)-induced diabetic NG neurons (133+2.2%, P<0.05). Extracellular application of caffeine (10 mM) or ionomycin (1 μM)to increase [Ca]i hyperpolarized membrane potential by 8.2+3 mV and 14+3.5 mV respectively and decreased neuronal input resistance to 56+3% and 42+11% of control. The I-V relationship analysis showed that the inhibitory action of ionomycin reversed close to the theoretical K+ channels reversal potential (-105 mV) suggesting mediation by activation of K+ channels. The hyperpolarizing effect of ionomycin (1 μM) was blocked when neurons were dialyzed with calcineurin autoinhibitory fragment (30 μM) or cyclosporine A (1 μM, a calcineurin inhibitor). A 36+5% reduction in input resistance (Rin) and hyperpolarized membrane potential (Vm) (-69 mV vs -54 mV, P<0.05) were observed in diabetic NG neurons. The current threshold to elicit action potential increased from 29+5 pA to 68+7 pA (P<0.05). These changes were accompanied by 52+6% increase in the 2 pore K+ channel TRESK mRNA and a 40+3% elevation in protein expression. We utilized these CN inhibitors to evaluate the role of CN in the activation of TRESK resulting in hyperpolarization of diabetic NG. Transfecting diabetic NG neurons with siRNA for TRESK normalized the electrophysiological properties of the NG neurons. Similarly, bath application of cyclosporine A or VIVIT peptide (0.2 nM) which inhibits the interaction between CN with TRESK at an NFAT-like docking site also reversed the reduction in Rin and hyperpolarized Vm of diabetic NG neurons. To provide direct evidence that diabetes alters vagal sensory inputs, neuronal discharge of single NG neurons innervating the stomach and the duodenum were recorded In Vivo in control and diabetic rats. Infusion of 60 pM CCK8 generated fewer spike potentials in diabetic rats compared to controls (4+1/10 s vs 14+1.2/10 s, P<0.05). Electroporation of TRESK siRNA or microinjection 1 μM of VIVIT peptide normalized the frequency response to CCK8 stimulation (60 pM). We conclude that hyperpolarization of the NG occurs in diabetes resulting in malfunctioning of the vagal afferent pathway. This is mediated by the Ca2+-calcineurin-TRESK K+ cascade in the NG.

Erythropoietin both protects from and reverses experimental diabetic neuropathy.

Erythropoietin (EPO) possesses generalized neuroprotective and neurotrophic actions. We tested the efficacy of recombinant human EPO (rhEPO) in preventing and reversing nerve dysfunction in streptozotocin (STZ)-induced diabetes in rats. Two days after STZ [60 mg/kg of body weight (b.w.), i.p.], diabetic animals were administered rhEPO (40 microg/kg of b.w.) three times weekly for 5 weeks either immediately (preventive) before or after a 5-week delay (therapeutic) after induction of hyperglycemia or at a lower dose (8 microg/kg of b.w. once per week) for 8 weeks (prolonged). Tail-nerve conduction velocities (NCV) was assessed at 5 and 11 weeks for the preventive and therapeutic schedule, respectively. Compared to nondiabetic rats, NCV was 20% lower after 5 weeks in the STZ group, and this decrease was attenuated 50% by rhEPO. Furthermore, the reduction of Na(+),K(+)-ATPase activity of diabetic nerves (by 55%) was limited to 24% in the rhEPO-treated group. In the therapeutic schedule, NCV was reduced by 50% after 11 weeks but by only 23% in the rhEPO-treated group. rhEPO treatment attenuated the decrease in compound muscle action potential in diabetic rats. In addition, rhEPO treatment was associated with a preservation of footpad cutaneous innervation, as assessed by protein gene product 9.5 immunostaining. Diabetic rats developed alterations in mechanical and thermal nociception, which were partially reversed by rhEPO given either in a preventative or therapeutic manner. These observations suggest that administration of rhEPO or its analogues may be useful in the treatment of diabetic neuropathy.

Electrophysiological changes in rat ventricular and atrial myocardium at different stages of experimental diabetes.

Action potential configuration in ventricular and atrial myocardium, as well as rate-dependent changes in ventricular action potential duration (APD) were studied and compared in healthy and diabetic rats. Diabetes was induced by a single injection of streptozotocin (STZ, 65 mg kg(-1) i.v.). Conventional microelectrode techniques were applied to record action potentials after the establishment of diabetes (2, 6, 10 and 18 weeks after STZ-treatment). Untreated age-matched animals were used as controls. Both depolarization and repolarization were significantly retarded following STZ-treatment. However, the time course of development of diabetic changes in atrial and ventricular myocardium was different. APD was significantly lengthened from week 2 of diabetes in ventricular, but only from week 6 in atrial preparations. In atrial myocardium, lengthening of APD was more pronounced at early rather than late phases of repolarization. The maximum rate of depolarization (Vmax) was significantly reduced from the 6th week of diabetes in both preparations. No differences were observed in action potential amplitude (except at week 18) and in the resting membrane potential in diabetic rats. Diabetic ventricular preparations showed a positive APD-frequency relationship at any level of repolarization, in contrast to control muscles, where APD25 and APD50 values lengthened. But APD75 and APD90 values were not changed significantly with increase in the pacing frequency. The results indicate that development of diabetic alterations are not fully identical in atrial and ventricular myocardium of the rat, probably owing to differences in density and kinetics of ionic currents responsible for atrial and ventricular action potentials.

L-Carnitine treatment improves brain stem auditory evoked potentials in diabetic rats

The effect of L-carnitine (LC) on brain stem auditory evoked potentials (BAEP), was examined in alloxan-diabetic rats. LC (200 mg kg-1, i.p., once daily) was given to diabetic rats starting from the third week after the induction of diabetes, lasting for 4 weeks. Age-matched non-diabetic rats served as controls. The latency of wave I and interpeak latency I-IV were measured once weekly. Diabetes-induced deficits in BAEP latencies (p < 0.05, diabetics vs non-diabetic controls) were improved after LC treatment (p < 0.05, LC-treated diabetic rats vs non-diabetic controls). Weight and glucose levels were not influenced by LC treatment. Our results suggest that LC had beneficial effects on diabetic central neuropathy but these effects are not associated with the regulation of glycaemia in alloxan-diabetic rats.