Changes In Diabetic Rats Research Articles

Mesoporous silica and alumina nanoparticles to improve drug delivery of pioglitazone on diabetic type 1 nephropathy in rats.

Diabetic nephropathy leads to end-stage renal disease. The present study aimed to evaluate the prophylactic effect of pioglitazone-loaded mesoporous silica and alumina scaffold on renal function and the underlying mechanisms in streptozotocin-induced diabetic rats. The mesoporous nanoparticles were synthesized by chemical methods from tetraethylorthosilicate and aluminum isopropoxide and characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. The soaking method was applied to load pioglitazone into the mesoporous silica and alumina. Subsequently, the most capable formulation was evaluated for lipid profile, blood glucose, renal function biomarkers, malondialdehyde, and kidney histopathological changes in diabetic rats. Pioglitazone loaded in the mesoporous included a superior release of about 80%. No interaction was observed in Fourier transform infrared spectroscopy and X-ray diffraction was shown crystalline. Scanning electron microscopy showed the size of the nanometer in the range of 100 - 300 nm. Mesoporous silica containing the drug significantly decreased urinary parameters, triglycerides, low-density lipoprotein, blood urea nitrogen, blood glucose, malondialdehyde, and creatinine. In addition, it showed increased high-density lipoprotein, significantly. The renal histopathological changes indicated improvement compared with the untreated diabetic group. It was concluded that the mesoporous was potent to serve as a promising drug carrier and a platform aimed at the delivery of poorly water-soluble drugs for improving oral bioavailability. Furthermore, it has the potential to provide a beneficial effect on the changes in diabetic parameters.

Exposure to fluoride exacerbates the cognitive deficit of diabetic patients living in areas with endemic fluorosis, as well as of rats with type 2 diabetes induced by streptozotocin via a mechanism that may involve excessive activation of the poly(ADP ribose) polymerase-1/P53 pathway

Epidemiology has shown that fluoride exposure is associated with the occurrence of diabetes. However, whether fluoride affects diabetic encephalopathy is unclear. Elderly diabetic patients in areas with endemic (n = 169) or no fluorosis (108) and controls (85) underwent Montreal Cognitive Assessment. Sprague-Dawley rats receiving streptozotocin and/or different fluoride doses were examined for spatial learning and memory, brain morphology, blood-brain barrier, fasting blood glucose and insulin. Cultured SH-SY5Y cells were treated with 50 mM glucose and/or low- or high-dose fluoride, and P53-knockdown or poly-ADP-ribose polymerase-1 (PARP-1) inhibition. The levels of PARP-1, P53, poly-ADP-ribose (PAR), apoptosis-inducing factor (AIF), and phosphorylated-histone H2A.X (ser139) were measured by Western blotting. Reactive oxygen species (ROS), 8-hydroxydeguanosine (8-OHdG), PARP-1 activity, acetyl-P53, nicotinamide adenine dinucleotide (NAD+), activities of mitochondrial hexokinase1 (HK1) and citrate synthase (CS), mitochondrial membrane potential and apoptosis were assessed biochemically. Cognition of diabetic patients in endemic fluorosis areas was poorer than in other regions. In diabetic rats, fasting blood glucose, insulin resistance and blood-brain barrier permeability were elevated, while spatial learning and memory and Nissl body numbers in neurons declined. In these animals, expression and activity of P53 and PARP-1 and levels of NAD+, PAR, ROS, 8-OHdG, p-histone H2A.X (ser139), AIF and apoptosis content increased; whereas mitochondrial HK1 and CS activities and membrane potential decreased. SH-SY5Y cells exposed to glucose exhibited changes identical to diabetic rats. The changes in diabetic rats and cells treated with glucose were aggravated by fluoride. P53-knockout or PARP-1 inhibition mitigated the effects of glucose with/without low-dose fluoride. Elevation of diabetic encephalopathy was induced by exposure to fluoride and the underlying mechanism may involve overactivation of the PARP-1/P53 pathway.

Curcumin Attenuates Ferroptosis and Ameliorates Erectile Function in Diabetic Rats by Activating Nrf2/HO-1 Pathway

Previous studies have shown that curcumin has a therapeutic effect on diabetic erectile dysfunction (ED), but the exact mechanism of action remains unclear. In order to ascertain the involvement of ferroptosis in diabetic ED and explore the underlying mechanism by which curcumin mitigates ferroptosis in penile endothelial cells under conditions of high-glucose stimulation, we conducted an investigation utilizing a rat model of diabetes induced by a high-fat diet and streptozotocin injection. The 40 male Sprague–Dawley rats were randomly divided into four groups: blank control, diabetes control, ferroptosis inhibitor treatment, and curcumin treatment. After 8 weeks, the erectile function of all rats was evaluated through electrical stimulation of the cavernous nerve. Histological and molecular changes of the cavernous body were analyzed using western blot and immunohistochemistry. Penile endothelial cells were then treated with appropriate concentrations of high glucose and curcumin to explore the mechanism of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling in curcumin’s ability to alleviate ferroptosis in endothelial cells stimulated by high glucose. According to research, diabetic rats experience a decrease in erectile function, damaged endothelial cells, and ferroptosis in tissues. However, curcumin treatment has been shown to be effective in improving erectile function and related tissue and molecular changes in diabetic rats. Furthermore, in vitro experiments have confirmed that curcumin can inhibit the occurrence of ferroptosis in penile endothelial cells that are stimulated by high glucose through Nrf2/HO-1 signaling. Curcumin has been found to improve the occurrence of penile ED in diabetic penile endothelial cells. This is achieved by inhibiting the level of ferroptosis, and the mechanism behind this improvement may be linked to the upregulation of the expression level of Nrf2/HO-1.

UPLC-Q-TOF/MS-based metabonomics reveals mechanisms for Holothuria leucospilota polysaccharides (HLP)-regulated serum metabolic changes in diabetic rats.

This study aimed to use metabolomic methods to explore how Holothuria leucospilota polysaccharides (HLP) improved metabolism disorders in the liver of Goto-Kakizaki (GK) rats with spontaneous type 2 diabetes. The results showed that HLP effectively improved the metabolic disorder. Based on KEGG functional analysis, five key biomarkers associated with bile acid metabolism were detected and screened (P<0.05). The results of serum total bile acid levels and liver damage in diabetic rats further showed the regulatory effects of HLP on bile acid metabolism. The results of bile acid-related gene expression in the liver showed that HLP inhibited liver farnesoidXReceptor - small heterodimer partner (FXR-SHP) signalling and increased the expression of bile acid synthesis genes (P <0.05). Our results explored the underlying mechanisms by which HLP accelerated cholesterol consumption to anti-hypercholesterolemia and anti-diabetic by inhibiting liver FXR-SHP signaling. HLP's effect on bile acid regulation provides insights into treating T2DM.

The effect of aqueous extract of Urtica Dioica and swimming activity on biochemical factors and renal tissue changes in diabetic rats

The effect of aqueous extract of Urtica Dioica and swimming activity on biochemical factors and renal tissue changes in diabetic rats

Tocotrienol-rich fraction reduces retinal inflammation and angiogenesis in rats with streptozotocin-induced diabetes

BackgroundDiabetic retinopathy (DR) is the second commonest microvascular complication of diabetes mellitus. It is characterized by chronic inflammation and angiogenesis. Palm oil-derived tocotrienol-rich fraction (TRF), a substance with anti-inflammatory and anti-angiogenic properties, may provide protection against DR development. Therefore, in this study, we investigated the effect of TRF on retinal vascular and morphological changes in diabetic rats. The effects of TRF on the retinal expression of inflammatory and angiogenic markers were also studied in the streptozotocin (STZ)-induced diabetic rats.MethodsMale Sprague Dawley rats weighing 200–250 g were grouped into normal rats (N) and diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (55 mg/kg body weight) whereas N similarly received citrate buffer. STZ-injected rats with blood glucose of more than 20 mmol/L were considered diabetic and were divided into vehicle-treated (DV) and TRF-treated (DT) groups. N and DV received vehicle, whereas DT received TRF (100 mg/kg body weight) via oral gavage once daily for 12 weeks. Fundus images were captured at week 0 (baseline), week 6 and week 12 post-STZ induction to estimate vascular diameters. At the end of experimental period, rats were euthanized, and retinal tissues were collected for morphometric analysis and measurement of NFκB, phospho-NFκB (Ser536), HIF-1α using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Retinal inflammatory and angiogenic cytokines expression were measured by ELISA and real-time quantitative PCR.ResultsTRF preserved the retinal layer thickness (GCL, IPL, INL and OR; p < 0.05) and retinal venous diameter (p < 0.001). TRF also lowered the retinal NFκB activation (p < 0.05) as well as expressions of IL-1β, IL-6, TNF-α, IFN-γ, iNOS and MCP-1 (p < 0.05) compared to vehicle-treated diabetic rats. Moreover, TRF also reduced retinal expression of VEGF (p < 0.001), IGF-1 (p < 0.001) and HIF-1α (p < 0.05) compared to vehicle-treated rats with diabetes.ConclusionOral TRF provided protection against retinal inflammation and angiogenesis in rats with STZ-induced diabetes by suppressing the expression of the markers of retinal inflammation and angiogenesis.

Ginkgo biloba extract protects against diabetic cardiomyopathy by restoring autophagy via adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin pathway modulation.

Studies demonstrated that Ginkgo biloba extract (GBE) played a cardioprotective role in diabetic conditions. Impaired autophagy is one of the mechanisms underlying diabetic cardiomyopathy (DCM). The effect of GBE on autophagy has been observed in several diseases; however, whether GBE can ameliorate DCM by regulating autophagy remains unclear. Here, we investigated the effect of GBE on DCM and the potential mechanisms regarding autophagy using a streptozotocin (STZ)-induced diabetic rat model and a high-glucose (HG)-stimulated H9C2 cell model. We demonstrated that GBE attenuated metabolic disturbances, improved cardiac function, and reduced myocardial pathological changes in diabetic rats. Impaired autophagy as well as dysregulation of the adenosine monophosphate-activated protein kinase/ mammalian target of the rapamycin (AMPK/mTOR) signaling pathway were observed in diabetic hearts, as evidenced by the reduced conversion of LC3B-I to LC3B-II along with excessive p62 accumulation, decreased AMPK phosphorylation, and increased mTOR phosphorylation, which could be reversed by GBE treatment. In vitro, GBE reduced the apoptosis induced by HG in H9C2 cells by activating AMPK and inhibiting mTOR to restore autophagy. However, this effect was inhibited by the AMPK inhibitor Compound C. In conclusion, the ameliorative effect of GBE on DCM might be dependent on the restoration of autophagy through modulation of the AMPK/mTOR pathway.

Histological assessment of cortical bone changes in diabetic rats

BackgroundDiabetes mellitus weakens bone strength due to deterioration of bone quality; however, the histological mechanisms are still unknown. We hypothesized that histological assessment of cortical bone would enable us to determine the cause of the bone strength reduction associated with diabetes mellitus. Our aim was to evaluate the histomorphometric changes of cortical bone associated with deterioration of intrinsic bone properties and bone quality in diabetes mellitus.MethodsWe compared the outcomes of mechanical tests, bone mineral density measured using micro-computed tomography, and histological assessments, by applying Villanueva’s bone stain, to the tibial bones of 40-week-old diabetic and control male rats.ResultsWith respect to mechanical testing, the maximum load and energy absorption were significantly lower in the diabetic than in the control group, although fracture displacement and stiffness were not significantly different between the two groups. Bone mineral density was significantly higher in the diabetic group than in the control group. Bone histomorphometry revealed that the diabetic rats had fewer osteocytes, greater cortical porosity, and increased mineralization in cortical bone compared with the control group.ConclusionsIncreased mineralization of the cortical bone with greater cortical porosity leads to a weakening of bone strength in diabetes mellitus.

Ameliorative Effect of Pongamia Pinnata on Histopathology of Vital Organs Involved in the Alloxan Induced Diabetic Rats

ABSTRACT The ameliorative effect of aqueous (PPAqExt) and alcohol (PPAlcExt) extracts of Pongamia pinnata on degenerative histopathological changes in diabetic rats were investigated. Rats were divided into six groups. 1. Control group (NC). 2. Diabetic control group (DC)3. PPAqExt (TD1) 4. PPAlcExt (TD2) 5. Standard Control group (SD) 6. Vehicle Control group (VC). Blood samples were collected for the detection of Glycosylated Hemoglobin (HbA1c) levels. The vital organs pancreas, liver, kidney, and testis were prepared for histopathological studies. Treatment with PPAlcExt produced a reduction in HbA1c levels (8.4%) compared to DC (13.63%). The histopathological microscopic examination of diabetic rats showed marked changes in all the vital organs ranging from mild to severe along with cell infiltration, degeneration, and necrosis. Treatment with both the extracts showed a reversal in structural and cellular integrity of the vital organs involved in the pathophysiology of diabetes mellitus.

Type 2 diabetes mellitus induced autophagic response within pulmonary tissue in the rat model.

Introduction: The current experiment aimed to address the impact of type 2 diabetes mellitus on autophagy status in the rat pulmonary tissue. Methods: In this study, 20 male Wistar rats were randomly allocated into two groups as follows: control and diabetic groups. To induce type 2 diabetes mellitus, rats received a combination of streptozotocin (STZ) and a high-fat diet. After confirmation of diabetic condition, rats were maintained for 8 weeks and euthanized for further analyses. The pathological changes were assessed using H&E staining. We also measured transforming growth factor-β (TGF-β), bronchoalveolar lavage fluid (BALF), and tumor necrosis factor-α (TNF-α) in the lungs using ELISA and real-time PCR analyses, respectively. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were monitored in diabetic lungs to assess oxidative status. We also measured the expression of becline-1, LC3, and P62 to show autophagic response under diabetic conditions. Using immunofluorescence staining, protein levels of LC3 was also monitored. Results: H&E staining showed pathological changes in diabetic rats coincided with the increase of TNF-α (~1.4-fold) and TGF-β (~1.3-fold) compared to those in the normal rats (P<0.05). The levels of MDA (5.6 ± 0.4 versus 6.4 ± 0.27 nM/mg protein) were increased while SOD (4.2 ± 0.28 versus 3.8 ± 0.13 U/mL) activity decreased in the diabetic rats (P<0.05). Real-time polymerase chain reaction (PCR) analysis showed the up-regulation of Becline-1 (~1.35-fold) and LC3 (~2-fold) and down-regulation of P62 (~0.8-fold) (P<0.05), showing incomplete autophagic flux. We noted the increase of LC3+ cells in diabetic condition compared to that in the control samples. Conclusion: The prolonged diabetic condition could inhibit the normal activity of autophagy flux, thereby increasing pathological outcomes.

Antidiabetic Potential of Ocimum gratissimum and Vernonia amygdalina Combined Extract in Streptozotocin-Induced Diabetic Rats

This study evaluated the antidiabetic effect of the ethanolic combined extract of Ocimum gratissimum and Vernonia amygdalina (OGVA) in streptozotocin-induced diabetic rats. The phytochemical content and safety level of OGVA in mice were assayed using standard methods and Lorke’s model of toxicity study, respectively. Graded OGVA doses were administered orally in streptozotocin-induced diabetic rats for 21 days. Indices of diabetes, oxidative stress, and tissue histology were assessed using biochemical kits and standard methods. The presence of various phytochemicals was identified with saponins (51.20 ± 0.11 mg/100 g) and flavonoids (40.70 ± 0.65 mg/100 g) recorded as the highest. Streptozotocin-induction, significantly (P &lt; 0.05) increased blood glucose (405.00 ± 3.65 mg/dl), aspartate aminotransferase (104.00 ± 6.57 U/l), alanine aminotransferase (90.70 ± 2.87 U/l), alkaline phosphatase (137.00 ± 4.18 U/l), urea (78.80 ± 2.04 mg/dl), and malondialdehyde concentration (5.03 ± 0.04 μmol/g) while animal weight, reduced glutathione (9.94 ± 0.75 μmol/g), superoxide dismutase (31.86 ± 0.61 U/g), and catalase (27.30 ± 0.38 μmol/min) were significantly (P &lt; 0.05) decreased. Histopathologic alterations were also observed in the liver and kidney. Treatment with OGVA significantly (P &lt; 0.05) improved these deleterious changes in diabetic rats. Oral administration of OGVA combined ethanolic leaf extract may alleviate diabetic-related biochemical alterations.

Berberine protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition involving the inactivation of the NLRP3 inflammasome

Accumulating evidence has implicated that berberine (BBR) has a beneficial effect on diabetic kidney disease (DKD), but its mechanism is not clear. The aim of this study was to assess whether berberine could alleviate tubulointerstitial fibrosis and attenuate epithelial-to-mesenchymal transition (EMT) and its possible molecular mechanism. High-fat diet (HFD) followed by injection of STZ was used to induce diabetic rats in vivo. After the onset of diabetes, rats were treated with either BBR or saline for 12 weeks. In vitro, the human renal proximal tubular epithelial cell line (HK-2) was exposed to high glucose, with or without BBR. The influence of berberine on renal tubulointerstitial histological changes, markers of epithelial-to-mesenchymal transition (EMT) and (NOD-like receptor pyrin domain-containing protein 3) NLRP3 inflammasome expression were examined. Results showed that in vivo, BBR could significantly ameliorate microalbumin and renal pathologic changes in diabetic rats. Immunofluorescence showed that BBR could inhibit EMT. Furthermore, BBR could down-regulate the level of the NLRP3 inflammasome in diabetic rats. Consistently, in vitro, BBR suppressed high glucose-induced EMT and activation of NLRP3 inflammasome in HK-2. Our study demonstrated that BBR could inhibit high glucose-induced EMT and renal interstitial fibrosis by suppressing the NLRP3 inflammasome. BBR might be used as a novel drug to ameliorate tubulointerstitial fibrosis in DKD.

Physiological and Biochemical Changes in Diabetic Rats Treated with Combined Extracts of Artemisia herba-alba and Anabasis syriaca

Physiological and Biochemical Changes in Diabetic Rats Treated with Combined Extracts of Artemisia herba-alba and Anabasis syriaca

Implications of lysyl oxidase-like protein 3 expression in the periodontium of diabetic rats.

Objectives Diabetes has been strongly associated with periodontal diseases. The periodontal ligament (PDL) has an abundant extracellular matrix (ECM). Lysyl oxidases (LOXs) are closely associated with various diseases caused by abnormal ECM functions, however, the role of LOXs in periodontal diseases induced by diabetes remains unclear.Methodology In this study, 8-week-old Zucker diabetic fatty rats were used to establish a type 2 diabetes mellitus (T2DM) model. After 9 and 16 weeks, hematoxylin and eosin (H&E), Masson’s trichrome, and immunohistochemical staining were performed.Results After 9 weeks, loose collagen fibers were found in the interradicular area of the diabetic group, in opposition to the control group. There were no significant differences in LOX expression between the diabetic and control groups (p>0.05). However, after 16 weeks, the diabetic group presented a disordered arrangement of the PDL, showing decreased collagen content and significantly increased lysyl oxidase-like protein 3 (LOXL3) expression when compared with the control group (p<0.05). This suggests that LOXL3 plays a significant role in periodontal histopathological changes in diabetic rats.Conclusion Our study showed elevated LOXL3 expression in the PDL of diabetic rats after 16 weeks, suggesting that LOXL3 may be involved in the occurrence and development of periodontal histopathological changes in diabetic rats. LOXL3 could be further used as an indicator for the early diagnosis of diabetic periodontitis in T2DM patients in clinical settings.

Evans blue staining to detect deep blood vessels in peripheral retina for observing retinal pathology in early-stage diabetic rats.

To observe and compare the statistical significance of superficial and deep vascular leakage in the pathological changes of the diabetic rats retina after the Evans blue (EB) perfusion, and utilize the modified whole-retina spreading method to make the slides while protecting the periphery of the retina. The Sprague-Dawley (SD) rats were randomly divided into 6 groups. Each group named as the normal groups for 4, 8, and 12wk and the diabetic groups for 4, 8, and 12wk. The EB was injected into the cardiovascular system of the rats at the different time points. The retina of each group was obtained for observation. The superficial vascular leakage was found in all 6 groups. The size of leakage area of superficial retinal blood vessels was (0.54±0.23)%, (0.65±0.11)%, and (0.58±0.10)% in normal group. No notable leakage was found in the deep blood vessels [(0.03±0.04)%, (0.03±0.05)%, and (0.03±0.05)%]. The deep retinal vascular leakage was found in the peripheral retina of diabetic rats. The size of leakage area of superficial retinal blood vessels in diabetic group were (0.53±0.22)%, (0.69±0.16)%, and (0.52±0.11)%. The leakage areas of deep blood vessels were (0.54±0.50)%, (1.42±0.16)%, and (1.80±0.07)% at 4, 8, and 12wk, respectively. There was a statistically difference of the leakage area between the 8th week and the 4th week of diabetes group (P=0.003). The statistically significant difference between the diabetes and the control groups was noted at 4wk and 8wk (P<0.001). The main retinal pathological changes of early-stage diabetic rats are the vascular leakage of the periphery of deep retina. Diabetic rats modeled after 8wk have semi-quantitative statistical difference compared with the normal rats, thus early intervention treatment research can start at this time point.

Urinary metabolites of type 2 diabetes rats fed with palm oil-enriched high fat diet

High fat diet (HFD) is one of the risk factors of obesity and diabetes. Recommended diet regimen for diabetes is difficult to abide by especially for HFD as it adds flavour to the taste buds. In this study, palm oil-enriched HFD and normal diet were fed to nicotinamide-induced type 2 diabetes rats, respectively for six weeks. Additionally, metformin, a common drug used to treat diabetes was given to rats under treatment groups. We evaluated the change of urinary metabolites of diabetes rats fed with palm oil-enriched HFD, and also after metformin treatment. Rats were divided into six-groups with different feeding diets, disease condition and with or without metformin treatment. Rats’ urine were collected at the end of six weeks feeding program and subjected to 1H-NMR and multivariate data analysis to evaluate their metabolite profiles. At the early phase of diabetes, metabolites changes in diabetic rats were associated with the disease itself. Our data showed that continuous consumption of HFD altered various metabolic pathways of diabetic rats and caused detrimental effects to the rats. On the other hand, metformin treatment combined with normal diet lessened the physiological impacts caused by diabetes condition.

Evaluating the Effects of Aloe vera Gel on Cerebellum Histomorphometrical Changes in Diabetic Male Rats

Background: Diabetes mellitus can lead to histomorphometrical changes in the brain. Recent studies have shown that Aloe vera gel has antioxidant and neuroprotective effects, which is independent of glucose-lowering effects. Objectives: The present study aimed to investigate the effects of A. vera gel on histomorphometrical changes of cerebellum following streptozotocin (STZ)-induced diabetic male rats. Methods: A total of 25 male Wistar rats were randomly allocated into five groups as follows: (1) the control group received normal saline; (2) A. vera gel group; (3) diabetic group; (4) treatment group diabetic rats, which received A. vera; and (5) diabetic rats which received insulin. A single dose of STZ [60 mg/kg; intraperitoneal (IP)] was used for the induction of diabetes in rats. All the treatments were administered daily for eight weeks. Subsequently, histomorphometrical changes were evaluated in the cerebellum of the rats. Results: The results showed that the number of granular and purkinje cells reduced in the cerebellum granulosa region, while the number of glial cells increased in the molecular region of the cerebellum in diabetic rats compared to the control group (P &lt; 0.05). These changes were improved in treated rats by insulin or A. vera. Also, the thickness of molecular, purkinje, granular, and white matter layers at the apex of lobules and depth of sulcus in the diabetic group had a significant reduction compared to other groups (P &lt; 0.001). Conclusions: Our results confirmed that improvement of the cerebellar tissue changes in diabetic rats following the use of A. vera gel is comparable to insulin. However, more investigations are required to determine the protective effects of A. vera gel against diabetes-induced cerebellum histomorphometrical changes.

Urinary Metabolites of Type 2 Diabetes Rats Fed With Palm Oil Enriched-High Fat Diet

High fat diet (HFD) is one of the risk factors to obesity and diabetes. Recommended diet regimen for diabetes is difficult to abide especially for HFD as it adds flavour to the taste buds. In this study, palm oil-enriched HFD and control diet (ND) were fed to nicotinamide-induced type 2 diabetes rats, respectively for six weeks. Additionally, metformin, a common drug used to treat diabetes was given to rats under treatment groups. We evaluated the change of urinary metabolites of diabetes rats caused by HFD, and also after metformin treatment. Rats were divided into six-groups with different feeding diets, disease condition and with or without metformin treatment. Rats’ urine were collected at the end of six weeks feeding program and subjected to 1H-NMR and multivariate data analysis to evaluate their metabolite profiles. At the early phase of diabetes, metabolites changes in diabetic rats were associated with the disease itself. Our data showed that continuous consumption of HFD altered various metabolic pathways of diabetic rats and caused detrimental effects to the rats. Metformin treatment combined with ND lessened the physiological impacts caused by diabetes condition. Funding Information: This research project was supported by USM RUI topdown grant (1001/PFARMASI/870034) funded by Universiti Sains Malaysia. Declaration of Interests: None to declare. Ethics Approval Statement: All experiment procedures were approved by the Animal Ethics Committee Universiti Sains Malaysia (USM/Animal Ethics Approval/2016/(717)).

Antioxidants Isolated from Elaeagnus umbellata (Thunb.) Protect against Bacterial Infections and Diabetes in Streptozotocin-Induced Diabetic Rat Model.

The increase in resistance of microbes against conventional drugs is currently a hot issue, whereas diabetes is another main cause of mortalities encountered throughout the world after cancer and heart attacks. New drug sources in the form of plants are investigated to get effective drugs for the mentioned diseases with minimum side effects. Elaeagnus umbellata Thunb. is a medicinal plant used for the management of stress related disorders like diabetes and other health complications. The active constituents of the chloroform extract derived from E. umbellata berries was isolated by silica gel column chromatography which were identified as morin, phloroglucinol, and 1-hexyl benzene through various spectroscopic techniques (electron ionization mass spectrometry, 1H-NMR, and 13C-NMR spectroscopy). The possible protective effects (antioxidant, antibacterial, and antidiabetic activity) of isolated compounds were evaluated using reported methods. Morin exhibited strong in vitro antiradical potential against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azinobis-3-ethylbenzothiazoline-6-sulfonic acid) radicals along with prominent antibacterial activities against selected bacterial strains (Escherichia coli, Bacillus cereus, Salmonella typhi, Klebsiella pneumonia, Pseudomonas aeruginosa and Proteus mirabilis). Among the isolated compounds the more potent one (morin) was assessed for its in vivo antidiabetic potential in streptozotocin-induced diabetic rat model. The in vivo effects observed were further confirmed in ex vivo experiments where the effect of isolated compound on antioxidant enzyme like glutathione peroxidase (GPx), total content of reduced glutathione (GSH), % DPPH inhibition, and the lipid peroxidation MDA (Malondialdehyde) level in pancreatic tissues homogenates were evaluated. In vivo morin at tested doses (2, 10, 15, 30 and 50 mg/kg body weight) significantly restored the alterations in the levels of fasting blood glucose level and body weight loss along with significant decrease in levels of cholesterol, triglycerides, low density lipoprotein, HbA1c level, and significantly increased the high-density lipoprotein in diabetic rats. Morin also effectively ameliorated the hepatic enzymes, and renal functions like serum creatinine. Morin significantly increased the antioxidant enzyme like GPx activity, GSH content, and % DPPH inhibition activity, while reduced the lipid peroxidation MDA (malondialdehyde) level in pancreatic tissues homogenates, and modification of histopathological changes in diabetic rats. Morin exhibited high antioxidant, antibacterial, and antidiabetic potentials as compared to phloroglucinol and 1-hexyl benzene, that could, therefore, be considered as a promising therapeutic agent to treat diabetes mellitus and bacterial infections.

Probiotic and resveratrol normalize GLP-1 levels and oxidative stress in the intestine of diabetic rats

BackgroundRecently, the use of incretins has been considered as a therapeutic target for diabetes. One of the important incretins in the improvement of diabetes is glucagon-like peptide (GLP-1), which is secreted by the gut and reduces the apoptosis of pancreatic β-cells and improves insulin sensitivity. In this experiment we determined the effects of resveratrol and probiotics on insulin resistance, oxidative stress, and GLP-1 in type 2 diabetes (T2D) rats. MethodsIn this study, 40 male Wistar male rats were divided into 5 groups: 1. Control group, 2. T2D, 3. T2D treated with probiotics, 4. T2D treated with resveratrol, 5. T2D group treated with probiotics and resveratrol. After four weeks, the intestine were removed for histopathological analysis, biochemical tests, and oxidative stress markers. ResultsProbiotics and resveratrol significantly decreased (p < 0.001) glucose and insulin resistance, and increased (p < 0.001) GLP1 and total antioxidant capacity compared to the diabetic group. Treatment with probiotics and resveratrol also returned intestinal histological changes in diabetic rats to normal. ConclusionResveratrol and probiotics appear to be effective in controlling T2D by increasing GLP-1 levels and reducing oxidative stress.