Levels In Normal Rats Research Articles

Hypoglycemic, antidiabetic and toxicological evaluation of leaf extract of Xylopia parviflora (A. rich.) Benth

BackgroundAlmost all Xylopia species have a long history of being used therapeutically in China due to their potent antioxidant properties. Xylopia parviflora (X. parviflora) is a relatively novel plant comprised mainly of beta-pinene, which has a rich history in Chinese medicine and is a principal active constituent in numerous Chinese herbs such as Rakkyo, the Chinese onions, Huasi Baidu Fang and Ru Xiang which are all native to China. ObjectiveThe study evaluated the antidiabetic potentials of the methanol leaf extract of X. parviflora and its toxicity profile. MethodsA modified version of the OECD guidelines was used to conduct acute and sub-chronic toxicity tests on the plant extract. The extract's effects on glucose, haematological, and biochemical components were evaluated using standard procedures. Using glibenclamide (10 mg/kg) and distilled water as positive and negative controls, the extract was tested for its antidiabetic activity in diabetic rats with streptozotocin induction at 50, 150, and 300 mg/kg for 28 days. Furthermore, vital organs underwent histopathological examination. Analysis of Variance (ANOVA) and the Dunnett multiple comparison tests were used for the statistical analysis, with a significance level of p < 0.05 ResultsPreliminary phytochemical analysis of the leaf extract revealed the presence of tannins, flavonoids, saponins, alkaloids, terpenoids, deoxy-sugars, and anthraquinones. The extract's median lethal dose (LD50) was greater than 2000 mg/kg in mice. Although it significantly reduced blood glucose levels in normal rats at 150 and 300 mg/kg doses, it had no toxic effects on the haematological and biochemical components of the collected blood samples. The extract produced an antidiabetic, non-dose-dependent impact on day seven at all the tested doses in streptozotocin-induced rats. On days 14, 21, and 28, however, glibenclamide and extract activity at all tested doses were comparable. At 200 mg/kg, the extract did not affect the histology of the liver, brain, kidney, or pancreas, but at 400 and 800 mg/kg, it had a slight and severe impact on these organs, respectively. ConclusionAccording to the study's findings, X. parviflora has antihyperglycemic activity and is non-toxic at low doses but may be harmful at high doses.

MiR-223-3p attenuates M1 macrophage polarization via suppressing the Notch signaling pathway and NLRP3-mediated pyroptosis in experimental autoimmune uveitis

Autoimmune uveitis is an intraocular inflammatory disease with a high blindness rate in developed countries such as the United States. It is pressing to comprehend the pathogenesis of autoimmune uveitis and develop novel schemes for its treatment. In the present research, we demonstrated that the Notch signaling pathway was activated, and the level of miR-223-3p was significantly reduced in rats with experimental autoimmune uveitis (EAU) compared with the level of normal rats. To investigate the relationship between miR-223-3p and Notch signaling, EAU rats received miR-223-3p-carrying lentivirus, miR-223-3p vector-carrying lentivirus (miR-223-3p-N), and γ-secretase inhibitor (DAPT), respectively. The results of Q-PCR, immunological experiments, and flow cytometry analysis all support the hypothesis that both miR-223-3p and DAPT, a Notch signaling pathway inhibitor, had similar inhibitory effects on the EAU pathological process. That is to say, they could both inhibit the activation of the Notch signaling pathway via modulating recombination signal binding protein-Jκ (RBPJ) to restore the polarization imbalance of M/M2 macrophages in EAU rats. In addition, miR-223-3p could also inhibit NLRP3 inflammasome activation and inflammasome-induced pyroptosis in ocular tissues. Taken together, our findings indicate that miR-223-3p serves as an important regulator in M1 macrophage polarization and pyroptosis, thereby alleviating the inflammatory response in uveitis.

1542-P: Commercially Available Aspartame-Based Sweetener Damages Morphology of Major Organs Both in Normal and Type 2 Diabetic Rats

Non-nutritive sweeteners (NNS) such as aspartame have become highly popular as sugar substitutes for diabetics. Majority of studies have reported controversial results and used aspartame in its pure form, which is not consumed by people practically. Hence, the present study was aimed at investigating the effects of commercially available aspartame-based sweetener on diabetes related parameters and its associated complications in both normal and type 2 diabetic rats. Seven-week-old male Sprague-Dawley rats were randomly divided into four groups, namely: Normal Control (NC), Toxicological Aspartame (TASP), Diabetic Control (DBC) and Diabetic Aspartame (DASP). Type 2 diabetes was induced experimentally in the DBC and DASP groups only and animals with non-fasting blood glucose levels &amp;gt;300 mg/dL were considered as diabetic. During 13 weeks experimental period, the control groups received normal drinking water, whilst TASP and DASP groups were given aspartame-containing NNS solutions, ad libitum, at concentrations equivalent to the sweetness of 20% and 10% sucrose solution, respectively. Treatment with toxicological aspartame resulted in significantly reduced serum fructosamine and creatinine levels in normal rats, when brain, heart, liver, kidney and pancreatic tissue morphologies were significantly damaged in both normal and diabetic rats. The data of this study suggest that although aspartame-based NNS may not have higher degree of detrimental effects on diabetes associated parameters, the significantly damaged morphology of the major organ tissues as well as deterioration of related serum biomarkers both in normal and diabetic conditions raises a concern of its use as a NNS in various food and food products. Disclosure S.N.Dlamini: None. S.Islam: None. Funding South African Sugar Association (Project 233)

Transient high salt intake causes epigenetic changes and leads to persistent inflammatory activation to produce “salt memory”

Transient high salt intake causes a sustained increase in blood pressure (BP) even after returning to a normal-salt diet, a phenomenon known as “salt memory.” However, the molecular mechanisms of this phenomenon remain to be elucidated. Dahl salt-sensitive (SS) rats were fed a high-salt (8% NaCl) or high-salt diet and treated with drugs for 8 to 16 weeks and then returned to a normal-salt diet for 3 months. This study investigated the molecular mechanisms of salt memory and its mediation of SS hypertension and renal damage. We show that transient high salt intake caused persistent elevation of BP and exacerbation of kidney damage in Dahl SS rats even after returning to a normal-salt diet. Both epigenetic changes and inflammatory activation also persisted after resumption of a normal diet. Arterial BP, renal injury and the inflammatory response returned to normal levels in rats administered mycophenolate mofetil (MMF) during the 8-week period of high salt intake, resulting in the disappearance of salt memory. However, the vasodilator hydralazine did not ameliorate kidney damage or inflammatory activation, although it decreased BP to control levels. Transient high salt intake increased histone 3 lysine 4 monomethylation (H3K4me1) levels at the nuclear factor κB (NF-κB) subunit p65 promoter in SS rats, promoting p65 gene transcription and NF-κB activation and further leading to a series of inflammatory responses. Our findings demonstrate that transient high salt-induced epigenetic changes and persistent inflammatory activation play important roles in salt memory and its mediation of SS hypertension and renal damage.

Protective Effect of Arjunakwatha and Arjunasheeta in Paracetamol-induced Kidney Injury in Rat Model

Background: Chronic kidney disease is now a global burden with an increased grade of morbidity and mortality due to the unavailability of particular medicines except for high-cost treatments like dialysis or kidney transplantation. Tribal people use their own indigenous preparation of medicinal plants for the prevention and treatment of kidney ailments. The present study was aimed at preparing Arjunakwaatha and Arjunasheeta, an indigenous preparation of the bark of Terminalia arjuna (TA) and its supplementation in the kidney injury rat model. Materials and Methods: In this study, rats were induced to kidney injury (KI) by intraperitoneal injection of paracetamol 15 mg/kg b.w. for 14 days and supplementation of Arjunakwaatha and Arjunasheeta with various doses continued the experimentation for 28 days. Results: Results showed that urea, creatinine, C-reactive protein (CRP), glutamine oxalic transaminase (GOT), glutamate pyruvate transaminase (GPT) in plasma, and malondialdehyde (MDA) in kidney tissue, urinary protein, and KIM-1 were significantly (p&lt;0.05) increased in kidney injury rats when compared to normal control rats. Supplementation of Arjunakwaatha and Arjunasheeta with kidney injury rats significantly (p&lt;0.05) decreased urea, creatinine, CRP, GOT, GPT, MDA, SOD, CAT, and GSH levels as compared to kidney injury rats. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed new low molecular weight urinary protein bands in kidney injury rats. The protective effects of Arjunakwaatha and Arjunasheeta present no band at this molecular level in normal rats. Conclusion: It has been concluded that Arjunakwaatha is the best indigenous preparation for kidney protection.

Transient gene therapy using cell cycle factors reverses renin-angiotensin-aldosterone system activation in heart failure rat model.

The loss of cardiomyocytes after myocardial infarction (MI) leads to heart failure. Recently, we demonstrated that transient overexpression of 4 cell cycle factors (4F), using a polycistronic non-integrating lentivirus (TNNT2-4F-NIL) resulted in significant improvement in cardiac function in a rat model of MI. Yet, it is crucial to demonstrate the reversal of the heart failure-related pathophysiological manifestations, such as renin-angiotensin-aldosterone system activation (RAAS). To assess that, Fisher 344 rats were randomized to receive TNNT2-4F-NIL or control virus seven days after coronary occlusion for 2h followed by reperfusion. 4months after treatment, N-terminal pro-brain natriuretic peptide, plasma renin activity, and aldosterone levels returned to the normal levels in rats treated with TNNT2-4F-NIL but not in vehicle-treated rats. Furthermore, the TNNT2-4F-NIL-treated group showed significantly less liver and kidney congestion than vehicle-treated rats. Thus, we conclude that in rat models of MI, TNNT2-4F-NIL reverses RAAS activation and subsequent systemic congestion.

Effects of dopamine transporter in the ventral tegmental area on sleep recovery after propofol anesthesia in sleep-deprived rats

ObjectivePrevious studies indicate that propofol can help with recovery from sleep deprivation and has anti-anxiety effects. However, the underlying neurochemical mechanism remains unclear. This study aimed to investigate the effects of dopamine transporter (DAT) in the ventral tegmental area (VTA) on sleep and anxiety recovery after propofol anesthesia in rats with 24 h total sleep deprivation (TSD). MethodsAdult male Sprague-Dawley rats were in natural sleep or sleep deprived for 24 h in a sleep deprivation rat system. The rats received propofol anesthesia (75 mg/kg, i.p.) or natural sleep. Dopamine transporter knockdown was performed by microinjection of AAV-DAT-RNAi vector. EEG was measured in each group to evaluate the subsequent sleep. The elevated plus maze test (EPMT) and open field test (OFT) were used to evaluate locomotion and anxiety level in rats. Immunofluorescence was used to verify virus location and transfection efficiency. ResultsCompared with NC group, the anxiety level of Propofol group showed no significant difference, but REM sleep decreased. Compared with the TSD group, the anxiety level of the TSD + Propofol group was reduced and the sleep recovery was closer to baseline. Compared with TSD + AAV-NC group, anxiety level and sleep time increased in TSD + AAVi group, REM increased within 24 h after sleep deprivation. The sleep time of TSD + AAVi + Propofol group was between those of TSD + AAV-NC group and TSD + AAVi group. TSD + AAV-NC + Propofol group had the least sleep time and the lowest anxiety level. Conclusion1. Propofol did not change anxiety level in normal rats, but reduced REM sleep, while it could accelerate sleep recovery and reduce anxiety level in sleep-deprived rats. 2. In sleep deprived rats with DAT knockdown, propofol improved sleep and anxiety levels more slowly, especially producing more REM rebound, suggesting that the improvement of sleep and anxiety levels in sleep-deprived rats with propofol may be related to DAT in VTA region.

Bolus Injection of Liraglutide Raises Plasma Glucose in Normal Rats by Activating Glucagon-like Peptide 1 Receptor in the Brain.

Diabetes is commonly treated with glucagon-like peptide-1 receptor (GLP-1R) agonists including liraglutide and others. However, liraglutide was found to raise plasma glucose levels in normal rats. The current study aims to determine how liraglutide causes this contentious condition in rats, both normal and diabetic. An adrenalectomy was performed to investigate the relationship between steroid hormone and liraglutide. To investigate the effect of central liraglutide infusion on blood glucose in rats, rats were intracerebroventricularly administrated with liraglutide with or without HPA axis inhibitors such as berberine and dexamethasone. The results showed that a single injection of liraglutide caused a temporary increase in blood glucose in healthy rats. Another GLP-1R agonist, Exendin-4 (Ex-4), increased blood sugar in a manner similar to that of liraglutide. The effects of liraglutide were also blocked by guanethidine pretreatment and vanished in normal rats with adrenalectomy. Additionally, central infusion of liraglutide via intracerebroventricular (icv) injection into normal rats also causes a temporary increase in blood glucose that was blocked by GLP-1R antagonists or the inhibitors such as berberine and dexamethasone. Similarly, central liraglutide treatment causes temporary increases in plasma glucose, adrenocorticotropic hormone (ACTH), and cortisol levels, which were reversed by inhibitors for the hypothalamic-pituitary-adrenal (HPA) axis. In normal rats, the temporary glucose-increasing effect of liraglutide was gradually eliminated during consecutive daily treatments, indicating tolerance formation. Additionally, liraglutide and Ex-4 cross-tolerance was also discovered in normal rats. Liraglutide was more effective in diabetic rats than in normal rats in activating GLP-1R gene expression in the isolated adrenal gland. Interestingly, the effect of liraglutide on glycemic control varied depending on whether the rats were diabetic or not. In normal rats, bolus injection of liraglutide, such as Ex-4, may stimulate the HPA axis, resulting in hyperglycemia. The cross-tolerance of liraglutide and Ex-4 provided a novel perspective on GLP-1R activation.

Perillyl alcohol and quercetin modulate the expression of non-coding RNAs MIAT, H19, miR-29a, and miR-33a in pulmonary artery hypertension in rats.

BackgroundNon-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play critical roles in the pathogenesis and progression of pulmonary artery hypertension (PAH). LncRNA H19, myocardial infarction-associated transcript (MIAT), miR-29a, and miR-33a have been suggested as potential targets for treating arterial hypertension. We explored the expression pattern of non-coding RNAs H19, MIAT, miR-29a, and miR-33a in monocrotaline (MCT)-induced PAH rats. Moreover, we investigated whether perillyl alcohol (PA) and quercetin (QS), two plant derivatives with beneficial effects on PAH-induced abnormalities, act through regulating the expression of these non-coding RNAs.MethodsMale Wistar rats (n = 30) were divided into five groups. MCT (60 mg/kg) was injected subcutaneously to induce PAH. PA (50 mg/kg daily) and QS (30 mg/kg daily) were administered three weeks after induction of PAH. H&E staining and qRT-PCR were performed to assess arteriole wall thickness and gene expression, respectively.ResultsRight ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) increased in MCT and MCT + Veh. groups compared to the control group (in both P < 0.001). QS and PA decreased RVSP and RVH significantly. Wall thickness and fibrosis score in the MCT group (score 3) increased compared to the control group (score 0). PA and QS ameliorated wall thickness and fibrosis to score 1 (mild). Also, the expression of miR-29a and miR-33a decreased in the PAH group (in both, P < 0.001). Treatment with PA and QS decreased the expression of H19 (P < 0.001) and MIAT (P < 0.01) and increased the expression of miR-29a (P < 0.01) and miR-33a significantly (P < 0.05 for QS and P < 0.001 for PA).ConclusionsThe beneficial effects of PA and QS on PAH-induced abnormalities were exerted through returning the dysregulated expression of H19, MIAT, miR-29a, and miR-33a to normal levels in rats with MTC-induced PAH. This study emphasized the therapeutic potential of PA and QS in PAH. However, more detailed investigations are needed to clarify the underlying molecular mechanisms.

Development of a Hypoparathyroid Male Rodent Model for Testing Delayed-Clearance PTH Molecules.

Parathyroid hormone (PTH) replacement is a promising approach in the management of hypoparathyroidism but long-acting analogues need to be developed. To date, animal models for testing PTH required parathyroidectomy by surgery. We have developed a nonsurgical rodent hypoparathyroid model and tested a delayed-clearance PTH molecule (DC-PTH). The aim of this study was to use cinacalcet to suppress calcium levels in normal rats and to reverse these effects with the administration of PTH or PTH analogues. Male Wistar rats were gavaged with either 30 mg/kg cinacalcet-HCl (cinacalcet) or vehicle only. Animals were then dosed with either single or repeated subcutaneous doses of PTH 1-34 or a DC-PTH at 20 nmol/kg. Control animals received vehicle only. Serum samples were analyzed for ionized calcium (iCa), phosphate, PTH, and DC-PTH. A pharmacokinetic-pharmacodynamic (PK-PD) model was built for cinacalcet, PTH 1-34, and DC-PTH using Phoenix64. Cinacalcet reduced iCa levels between 2 and 24 hours, returning to baseline by 72 hours post dose with nadir at 8 hours (analysis of variance P < .001), associated with a fall in rat PTH. For phosphate there was a variable biphasic response. Single-dose PTH abrogated the cinacalcet-induced fall in iCa for up to 2 hours. DC-PTH prevented the fall in iCa from 4 hours post dose and gave a prolonged response, with iCa levels quicker to return to baseline than controls. DC-PTH has a half-life of 11.5 hours, approximately 44 times longer than human PTH 1-34. The PK-PD models defined the reproducible effect of cinacalcet on iCa and that DC-PTH had prolonged biological activity. The administration of cinacalcet provides a robust and reproducible nonsurgical animal model of hypoparathyroidism. DC-PTH holds promise for the treatment of hypoparathyroidism in the future.

Pharmacodynamic and pharmacokinetic interaction of losartan with glimepiride-metformin combination in rats and rabbits.

OBJECTIVES:The presence of comorbidities such as cardiovascular disease, peripheral vascular disease, and chronic renal disease, or and the prevention of these ailments in diabetics, frequently demands multiple drug treatments, increasing the risk of drug-drug interactions (DDIs). The current study was focused on identifying possible DDIs on concomitant administration of losartan, a drug used to regulate hypertension along with a combination of glimepiride + metformin, widely used to treat diabetes mellitus. Possible pharmacodynamic and pharmacokinetic interactions were observed for, following single-dose as well as multiple-dose treatment protocols in normal and alloxan-induced diabetes in albino Wistar rats and rabbits.MATERIALS AND METHODS:Blood samples from surviving rats/rabbits obtained through orbital venous sinus bleeding/marginal ear vein bleeding, respectively, at predetermined intervals and put through to biochemical estimations of sugar level in the blood by Glucose oxidase/peroxidase method; insulin levels in serum using the enzyme-linked immunosorbent assay and serum glimepiride levels using the high-performance liquid chromatography.RESULTS AND DISCUSSION:Losartan, when treated as a single drug, resulted in a slight lowering of blood glucose levels in normal rats, diabetic rats and normal rabbits. Hypoglycemic activity of a combination of glimepiride + metformin was enhanced when losartan was co-administered as a single dosage schedule as well as a multiple dose schedule as indicated by a reduced blood glucose level and enhanced levels of insulin in rats as well as in rabbits. Serum glimepiride levels were also higher and pharmacokinetic parameters of glimepiride including mean residence time, Cmax, T1/2, AUMC0-∞, AUMC0-t, and AUC0-∞, were significantly higher, whereas its clearance was decreased in the two regimens of losartan that was followed.CONCLUSION:It can therefore be concluded, that in diabetics with hypertension as a comorbidity condition, co-administration of losartan with glimepiride + metformin should be avoided or the dosage of a combination of glimepiride + metformin needs to be tittered to avoid recurrence of hypoglycemic episodes.

Antidiabetes effect of Noni Fruit (Morinda citrifolia L.) on mice with Oral Glucose Tolerance Method and Streptozotocin Induction Method

Diabetes mellitus (DM) is a problem that deserves attention because of its increasing prevalence every year. The prevalence of DM based on WHO in 2030 is predicted to reach 366 patients. Epidemiologically, it is estimated that in 2030 the prevalence of DM in Indonesia reaches 21.3 million people. The purpose of this study was to determine the effectiveness of glycosides from noni fruit on reducing blood sugar levels in normal rats induced by diabetes by the method of glucose tolerance and induction of streptozotocin (STZ). Antidiabetic effect testing was divided into 8 groups namely 4 groups for oral glucose tolerance test in male mice (positive control group, negative control group, glycoside control group, and normal group), 4 other groups for testing with STZ induction (positive control group, positive control group, negative control, glycoside control group, and normal group). Oral glucose tolerance test results on normal mice showed that glycosides from noni fruit (Morinda citrifolia L.) gave significantly different results with negative controls at minute 30 is 0.036 (p &lt;0.05) and were not significantly different from positive controls (0.462) subsequently at 120 minutes the results showed that the glycoside group was significantly different from the negative group (0.028) and not significantly different from the positive group (0.261). Tests with STZ induction method showed that the decrease in the level of blood sugar induced by the glycoside group was not significantly different (p&gt; 0.05) with the positive group on day 1 (0.056), day 3 (0.168), and day 7(0.141) so that it could be concluded that the glycosides from Noni fruit with a dose of 150mg/kg body weight provides antidiabetic activity.

Electroacupuncture and Moxibustion Modulate the BDNF and TrkB Expression in the Colon and Dorsal Root Ganglia of IBS Rats with Visceral Hypersensitivity.

Objective To evaluate the effects of electroacupuncture and moxibustion on brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase receptor B (TrkB) protein and mRNA expressions in the colon and dorsal root ganglia of IBS rats with visceral hypersensitivity and to explore their underlying therapeutic mechanisms. Method Forty Sprague Dawley rats were randomly divided into normal, model, model + mild moxibustion (MM), model + electroacupuncture (EA), and model + pinaverium bromide (PB) groups, with eight rats in each group. Chronic visceral hypersensitive IBS rat models were established by colorectal distension (CRD) with mustard oil clyster. Rats in the MM and EA groups, respectively, received moxibustion and electroacupuncture treatments on the Tianshu (ST25) and Shangjuxu (ST37) acupoints once daily for 7 days, and rats in the PB group received pinaverium bromide by oral gavage once daily for 7 consecutive days. After treatment, rats underwent abdominal withdrawal reflex (AWR) scoring under CRD and colon histopathological examination. Immunohistochemistry and real-time quantitative PCR (RT-qPCR) were used to study the protein and mRNA expressions of BDNF and TrkB in the rat colon and dorsal root ganglia. Results Compared with the normal group, AWR scores and body weight were clearly increased in the model group rats (both P < 0.01). The body weights were significantly elevated (P < 0.01, P < 0.05), but the AWR scores were reduced (P < 0.05, P < 0.01), after electroacupuncture and mild moxibustion treatment. Compared with levels in normal rats, BDNF and TrkB protein and mRNA expressions were significantly elevated in the IBS model rats (P < 0.01) but were downregulated after mild moxibustion, electroacupuncture, and Western medicine treatment (P < 0.01). Conclusion Electroacupuncture and moxibustion improved visceral hypersensitivity of IBS rats possibly by reducing BDNF and TrkB protein and mRNA expressions in the colon and dorsal root ganglia.

Opuntia dillenii (Ker Gawl.) Haw., Seeds Oil Antidiabetic Potential Using In Vivo, In Vitro, In Situ, and Ex Vivo Approaches to Reveal Its Underlying Mechanism of Action.

Opuntia dillenii Ker Gawl. is one of the medicinal plants used for the prevention and treatment of diabetes mellitus (DM) in Morocco. This study aims to investigate the antihyperglycemic effect of Opuntia dillenii seed oil (ODSO), its mechanism of action, and any hypoglycemic risk and toxic effects. The antihyperglycemic effect was assessed using the OGTT test in normal and streptozotocin (STZ)-diabetic rats. The mechanisms of action were explored by studying the effect of ODSO on the intestinal absorption of d-glucose using the intestinal in situ single-pass perfusion technique. An Ussing chamber was used to explore the effects of ODSO on intestinal sodium-glucose cotransporter 1 (SGLT1). Additionally, ODSO’s effect on carbohydrate degrading enzymes, pancreatic α-amylase, and intestinal α-glucosidase was evaluated in vitro and in vivo using STZ-diabetic rats. The acute toxicity test on mice was performed, along with a single-dose hypoglycemic effect test. The results showed that ODSO significantly attenuated the postprandial hyperglycemia in normal and STZ-diabetic rats. Indeed, ODSO significantly decreased the intestinal d-glucose absorption in situ. The ex vivo test (Ussing chamber) showed that the ODSO significantly blocks the SGLT1 (IC50 = 60.24 µg/mL). Moreover, ODSO indu\\ced a significant inhibition of intestinal α-glucosidase (IC50 = 278 ± 0.01 µg/mL) and pancreatic α-amylase (IC50 = 0.81 ± 0.09 mg/mL) in vitro. A significant decrease of postprandial hyperglycemia was observed in sucrose/starch-loaded normal and STZ-diabetic ODSO-treated rats. On the other hand, ODSO had no risk of hypoglycemia on the basal glucose levels in normal rats. Therefore, no toxic effect was observed in ODSO-treated mice up to 7 mL/kg. The results of this study suggest that ODSO could be suitable as an antidiabetic functional food.

Effect of Furosemide and Spironolactone on urinary zinc excretion in rats

Background: Zinc deficiency is associated with numerous diseases including hypertension, diabetes, obesity, immune dysregulation, cancer, depression and congenital anomalies. There are many reasons of zinc deficiency including some medications. If zinc supplementation is used with these medicines than many diseases can be prevented.&#x0D; Subjects and methods: This experimental study was planned to observe the effect of single diuretic dose of furosemide and spironolactone on zinc urinary excretion and blood levels in normal rats. Eighteen adult healthy male Sprague Dawley rats were randomly divided into three groups. After saline load rats were given distilled water, furosemide (10 mg/kg) and spironolactone (20 mg/kg) as single oral dose. Blood and urine samples were collected after five hours and analysed for zinc concentration by flame atomic absorption spectrophotometer.&#x0D; Results: Single oral dose of furosemide and spironolactone highly significantly increased urinary zinc excretion (p-value &lt;0.001 vs normal control), and increased blood zinc level (p-value &lt;0.001 vs. normal control). Value of both variables were significantly higher in furosemide-treated group (p-value &lt;0.001 vs. furosemide-treated).&#x0D; Conclusion: Results of this research conclude that furosemide and spironolactone increase urinary zinc excretion when used for short period. It is also postulated that blood zinc concentration is not reliable measure to assess the zinc status of the body because its level shows compensatory rise during deficiency states.

Comparison of Hypoglycemic and Antioxidant Activities of the Compounds Isolated from Ficus hispida Linn. and Ficus pomifera Wall

Background: Traditional knowledge has been a legacy of the past to the present. Barks of Ficus hispida Linn. and leaves of Ficus pomifera Wall. (Moraceae) have been used traditionally for the treatment of diabetes in North-east India and many other places. As many drugs have been developed from traditional plants, the authors have taken up the plants for the study of hypoglycemic activity. Objective: To investigate the hypoglycemic activities of the triterpenoids isolated from the plants and their antioxidant activities. Methods: The bioactive compounds were determined by biochemical analysis, antioxidant activity using DPPH method. Hypoglycemic activity was detected using glucose tolerance test in normal rats and alloxan induced diabetic rats with Gliclazide as standard. Results: The biochemicals and trace elements were present in appreciable amounts. Triterpenoids, (1-5), from F. pomifera and 19-hydroxyphlogacantholide (6), 3-O-[ß-D-glucopyranosyl-(1’→2’)-α- L-rhamnopyranosyl-phlogacanthoside] (7) and galanolactone (8) along with stigmasterol (9), stigmasta- 5,22-dien-7-on-3ß-ol (10), 5-(decahydro-1,1,4a-trimethyl-6-methylene-5-yl)-3-methylpent-2- enal (11), stigmasterol glucoside (12) and stigmast-4-en-3-one (13) from F. hispida Linn., respectively, were isolated. The different extracts of the barks and leaves of these plants along with the isolated compounds had antioxidant and hyploglycemic activities. Conclusions: The five triterpenoids (1-5) were isolated from the methanol extract of the leaves of F. pomifera, and compounds (6-13) were isolated from the chloroform extract of the barks of F. hispida. Methanol extract of the leaves of F. pomifera and the chloroform extract of the barks of F. hispida; compounds (1-13) isolated from these two plants reduced DPPH free radicals in a concentrationdependent manner. It was also observed that the methanol and chloroform extracts of the plants, F. pomifera and F. hispida respectively, and the compounds (1, 6 &amp; 7) exhibited anti-diabetic properties and also caused a highly significant reduction in the blood glucose levels of normal rats.

Effect of the pineal gland on 5-hydroxytryptamine and γ-aminobutyric acid secretion in the hippocampus of male rats during the summer and winter

Abstract Objective The present study aimed to investigate the effect of seasonal variation on neurotransmitter release in the hippocampus of normal rats and rats with pineal excision. Methods Two time points, the summer and winter solstice, which are the longest and shortest days of the year, respectively, were selected. Male Sprague–Dawley rats that underwent a sham operation without pineal excision were included as a control group. The concentrations of 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) were determined by radioimmunoassays and enzyme-linked immunosorbent assays, respectively. Results In the winter, the 5-HT and GABA levels in normal rats exhibited a significant difference compared with those in the operation group (P Conclusion The seasonal rhythm of neurotransmitter secretion by the hippocampus (5-HT and GABA) consisted of elevation during the summer and reduction during the winter. During the winter, the pineal gland exhibited a reverse regulatory effect on the secretion of 5-HT and GABA in the hippocampus, and it exhibited seasonal selectivity with regard to the regulation of 5-HT.

Impact of caffeic acid phenylester on nitric oxide synthase and arginase in rats intoxicated with nitrites

This study investigated the impact of the caffeic acid phenyl ester (CAPE) on the enzymes detoxifying nitrites induced liver injury in rats. Male albino rats were given CAPE 3 mg CAPE/kg b.wt (i.p.) for last 4 weeks during 2 g/L NaNO2 drinking nitrites for 8 weeks to evaluate the protective effect of CAPE. Another group was treated with the same dose of CAPE i.p for 4 weeks after administration NaNO2 for 4 weeks. Data obtained showed that rats administrated nitrite showed a significant elevation of serum and liver NO and as compared with control. Serum and liver NO levels alleviated to the normal level in rats treated with CAPE. CAPE administration as protected or treated caused a reduction in liver MDA while liver GSH, catalase, and GST were significantly increased as compared with rats drinking nitrites Rats treated with CAPE showed an enhancement in arginase activity as a mechanism to overcome the nitrite toxicity in the liver. In addition, histological observation revealed normal hepatocytes with reduced infiltration of neutrophil in rats treated with CAPE. Conclusion: The CAPE treated rats ameliorated the toxicity of nitrites by inhibiting oxidative stress and modulation of enzymes detoxifying nitrites.

Влияние активации ванилоидных рецепторов эводиамином на содержание кальцитонин-ген-родственного пептида в крови крыс в норме и при гипертензии, вызванной потреблением фруктозы

Background: Calcitonin-gene-related peptide (CGRP) is a neurotransmitter of capsaicin-sensitive nerves, one of the most powerful vasodilators, in mediation of vasoactive action of which the nitrogen oxide (NO) takes part. The aim of this study was to evaluate the CGRP and NO blood levels in normal rats and rats with fructose-induced hypertension, with unaffected transient receptor potential vanilloid 1 (TRPV1) receptors, and after the administration of their agonist evodiamine. Male Wistar Rats were given to drink either 12.5% fructose solution or tap water (control) for 10 weeks. Evodiamine (10 mg/kg), a TRPV1 agonist, was administered intraperitoneally every other day, for 2 weeks, starting 8 weeks after the start of the fructose intake. The systolic blood pressure was measured using a noninvasive technuque. The glucose levels, fasting and 1 hour after the glucose load (2g/kg, i.p), were measured by a glucometer in the blood sampled from the caudal vein. Concentrations of CGRP, NO metabolites (NOx), triglycerides (TG) and lipid peroxidation products (LPO) were measured in the blood serum of rats. The fructose consumption led to hypertension, impaired glucose tolerance, increased the blood levels of LPO products and TG, and decreased the CGRP blood content. The evodiamine introduction to fructose-consuming rats restored the blood CGRP content to the control values, reduced the blood pressure, LPO products and TG levels, and improved the glucose tolerance. The NOx levels did not differ from the control in all groups. We suggest that CGRP is involved in the development of the fructose-induced hypertension and in mediating the therapeutic effect of the evodiamine.

Diuretic and Antidiuretic Activities of Ethanol Extract and Fractions of Lagopsis supina in Normal Rats.

Lagopsis supina is a well-known traditional Chinese medicine and used as an agent for diuresis in China for centuries. This is the first time to evaluate the diuretic activity of the ethanol extract of L. supina (LS) and its four fractions (LSA, LSB, LSC, and LSD) in normal rats. After the administration of LS-H, LS-M, LSB-H, and LSC-L, the urine output of the rats was significantly increased, while the urine excretion was significantly reduced after treatment with LSB-L. The urine Na+ excretion was remarkably increased with LS-H, LS-M, LSA-H, LSA-L, LSB-H, LSC-L, and LSD-L, and the urine K+ excretion was significantly increased after administration of LS-H and LSB-H. Moreover, the urine Na+ and K+ excretion was significantly reduced after treatment with LSC-H and LSD-H. However, the urine pH values and urine and serum Na+-K+-ATPase levels did not show remarkable change after administration of LS or its four fractions in comparison with the control group. On the contrary, LS and its four fractions can suppress the renin-angiotensin-aldosterone system (RAAS), including ADH arrest by LSB-H, LSB-L, LSC-L, LSD-L, and LSD-H and ALD arrest by LSD-L, as well as promote ANP release by LS-M, LSB-H, LSC-H, and LSD-H, while furosemide can suppress only arrest of ADH within 24 h compared with the control group. In addition, LS and its four fractions did not change the urine and serum TNF-α and IL-6 levels in normal rats within 24 h. This study will provide a quantitative basis for explaining the natural medicinal use of LS as a diuretic agent for edema and promoting the diuretic process.