Endurance Exercise Prevented Diabetic Cardiomyopathy through the Inhibition of Fibrosis and Hypertrophy in Rats.

Background: Exercise training could be essential in preventing pathological cardiac remodeling in diabetes. Therefore, the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) singly or plus metformin on diabetes-induced cardiomyopathy were investigated in this study. Methods: Forty-nine Wistar rats (male) were recruited. Seven groups of animals were treated for six weeks as control, diabetes, MICT (15 m/min, 40 min/day), HIIT (20 m/min, 40 min/day), metformin (300 mg/kg), HIIT+metformin (Met-HIIT), and MICT+metformin (Met-MICT). The metformin was orally administered with an intragastrical needle, and the exercised rats were trained (5 days/week) with a motorized treadmill. Metabolic parameters, echocardiographic indices, histopathology evaluation, and assessment of gene expression connected with cardiac fibrosis, hypertrophy, mitochondrial performance, and intracellular calcium homeostasis were investigated. Results: Our results demonstrated that all the interventions prevented weight loss and enhanced heart weight/body weight ratio and fasting plasma glucose in diabetic rats. Both types of exercise and their metformin combinations improved diabetic animals' echocardiography indices by enhancing heart rate, fractional shortening (FS), ejection fraction (EF) and reducing end-systolic and end-diastolic diameter of left ventricular (LVESD and LVEDD). Gene expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), transforming growth factor (TGF)- ß , and collagen increased in the diabetes group. In contrast, the gene expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α ), AMP-activated protein kinase (AMPK), ryanodine receptors (RyR), and Ca 2 + ATPase pump of the sarcoplasmic reticulum (SERCA) was reduced in diabetic animals. Exercise training alone or in combination with metformin reversed these changes. Moreover, diabetes-induced cardiac fibrosis was ameliorated in treated groups. All indicators of diabetic cardiomyopathy were improved more in the Met-HIIT group than in other groups. Conclusions: Exercise training, notably with metformin combination, alleviated diabetes-induced cardiac complications. The beneficial effects of exercise could be related to improving pathological cardiac remodeling and enhancing cardiac function.

Effects of moderate exercise on lipopolysaccharide-induced inflammatory responses in rat's cardiac tissue.

The effects of moderate exercise on cardiac tissue inflammation, oxidative stress markers and apoptosis in lipopolysaccharide (LPS)-administered rats were evaluated. Wistar rats were divided into three groups (N = 8): (1) control; (2) LPS (1 mg/kg); and (3) LPS + moderate training (LPS + EX: 15 m/min, 30 min/day, for 9 weeks (week 1-9)). LPS was injected intraperitoneally for 5 days during week 9. Finally, the rats' heart were removed for biochemical and expression assessments. LPS increased the levels of tumor necrosis factor α (TNF-α), interleukin (IL)- 1ß, C-reactive protein (CRP), malondialdehyde (MDA) and nitric oxide (NO) metabolites in cardiac tissue, but decreased thiol contents and catalase (CAT) and superoxide dismutase (SOD) activity in cardiac tissue compared to the control group (p < 0.05-p < 0.001). In LPS + EX group, the level of NO metabolites was increased (p < 0.05) and thiol contents were decreased (p < 0.001) compared to the control group. Moderate training decreased the levels of TNF-α, IL-1ß, CRP and NO metabolites while increased CAT activity in the LPS + EX group compared to the LPS group (p < 0.05-p < 0.001). The mRNA level of BAX in the LPS group and the BCL2/BAX ratio in both LPS and LPS + EX groups increased compared to the control group (p < 0.05-p < 0.01). These results indicated that moderate training improved LPS-induced deleterious effects on cardiac tissue by attenuating proinflammatory cytokine levels, apoptosis and oxidative damage.

A case report of left atrial myxoma presenting with amnesia.

BACKGROUND: Primary cardiac tumors are rare, and approximately 90% of them are benign. Myxoma is the most common type of these tumors occurring in the left atrium in 75-85% of cases. The tumor can cause the left atrio-ventricular valve obstruction and embolization phenomenon. Case presentation We reported a case of 54-year-old man with complaints of dyspenea and amnesia. In our patient, transthoracic echocardiography revealed a mass of 28*63 mm attached to the upper intra-atrial septum, which was prolapsing through the mitral valve into the left ventricle during diastole, being indicative of the left atrial myxoma. On examination, he was alert and conversant, and no pathological abnormality was observed in the examination of cardiovascular, gastrointestinal, respiratory, hepatic, renal and nervous systems. After myxoma diagnosis, the tumor was removed under cardiac surgery and discharged under good conditions. In the telephone follow-up after discharge, the patient recovered and did not report the disease and surgery complications. CONCLUSIONS: Patients with cardiac myxoma are usually asymptomatic, but they may have manifestations related to the embolism phenomenon or intracardiac obstruction. Therefore, myxoma may represent an emergency. Surgery should be performed as soon as possible. If surgery is delayed, the patient may suffer from serious and irreversible complications, such as stroke and cardiac arrest.

Diabetic cardiomyopathy in rats was attenuated by endurance exercise through the inhibition of inflammation and apoptosis.

Diabetic cardiomyopathy (DCM), as a ventricular dysfunction, is one of the main causes of death in diabetic patients. Former evidence revealed the beneficial effects of exercise on cardiovascular complications of diabetes. We aimed to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on DCM. Male Wistar rats were divided into control, diabetic, metformin (300 mg/kg), HIIT, MICT, metformin + HIIT, and metformin + MICT diabetic groups. Serum biochemical, inflammatory, and oxidative stress indicators, gene expression of BCL2 and BAX, and histopathologic changes of cardiac tissue were assessed. Our analysis revealed an increase in fasting blood sugar (FBS), creatine kinase MB (CK-MB), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) in diabetes. Also, the superoxide dismutase (SOD) and catalase (CAT) activity, and the total thiol were decreased, in contrast, malondialdehyde (MDA) levels increased in the cardiac tissue of the diabetic group. All of these changes were significantly ameliorated in diabetic animals treated with exercise and metformin + exercise. The level of tumor necrosis factor-α (TNF-α) and Interleukin-1ß (IL-1ß), as well as the infiltration of inflammatory cells, were decreased in the heart of all exercise training groups. Up-regulation of BCL2 and down-regulation of BAX gene expressions were observed in the cardiac tissue of all exercise-treated groups. In conclusion, HIIT and MICT exercises are effective in preventing DCM development. Exercise training, besides improving oxidative stress and inflammation in cardiac tissue, alleviates cardiac damage by modulating the apoptotic gene expression in diabetic rats.

Cardioprotective effect of cedrol in an inflammation systemic model induced by lipopolysaccharide: Biochemical and histological verification.

Introduction: Evidence declared lipopolysaccharide (LPS) initiates inflammatory responses by stimulating the abandon of cytokines, which may perturb organ function. On the other side, it has been suggested Cedrol has potential properties, including anti-inflammatory and anti-oxidative activities. Herein, this study was done to assess the protective effect of Cedrol against LPS-associated heart damage. Methods: Thirty-five rats (200-250 g) were sorted into five groups, including control, LPS, LPS-Cedrol 7.5 mg/kg, LPS-Cedrol 15 mg/kg, and LPS-Cedrol 30 mg/kg groups. Cedrol was administrated through injected intra-peritoneally for two weeks. The heart tissues were removed and malondialdehyde (MDA) as a lipid peroxidation marker, superoxide dismutase (SOD), and catalase (CAT) as antioxidant markers were assessed. Furthermore, the interleukin (IL)-6 level in cardiac tissue was measured and Masson's trichrome methods were employed to appraise cardiac inflammation and fibrosis, respectively. Results: Inflammation induced by LPS was significantly accompanied by myocardial fibrosis which was shown by Masson's trichrome staining (P<0.001). In addition, LPS administration enhanced the MDA level while it diminished the activity of anti-oxidant markers such as CAT and SOD (P<0.001 for all cases). In the histological results, Cedrol improved LPS-induced inflammation and cardiac fibrosis (P<0.01 to P<0.001). Cedrol also enhanced CAT and SOD activities, whereas declined MDA level in the cardiac tissue (P<0.01 to P<0.001). Conclusion: The current findings proposed that the administration of Cedrol exerted a protective role in LPS-associated heart damage by reducing inflammation, cardiac fibrosis, and oxidative stress.

Antioxidant effect of Achillea wilhelmsii extract on pentylenetetrazole (seizure model)-induced oxidative brain damage in Wistar rats.

An important role for oxidative stress both as a consequence and as a cause of epileptic seizures has been suggested. Since Achillea wilhelmsii (A. wilhelmsii) has been considered to have the antioxidant effects as well as central nervous system depressant properties, the anti-seizure effects of the plant extract in addition to its effects on brain tissues oxidative damage were investigated in pentylenetetrazole (PTZ)-induced seizures model. Male Wistar rats were divided into 5 groups: (1) Control, (2) PTZ, (3-5) A. wilhelmsii extract groups (AWE). The animals in groups 2-5 were treated with saline or AWE (100, 200 or 400 mg/kg) before single injection of PTZ (90 mg/kg). Latency to first minimal clonic seizure (MCS) and the first generalized tonic-clonic seizures (GTCS) were recorded. The brain tissues were then removed for biochemical measurements. MCS latencies in extract treated groups were not different from PTZ group. The animals treated by 200 mg/kg of AWE had a significant higher GTCS latency in comparison with PTZ group (P < 0.001). The MDA levels in PTZ group were significantly higher and the total thiol concentrations were lower than control animals. Pretreatment with all 3 doses of the extract resulted in a significant reduction in the MDA levels (P < 0.05, P < 0.01 and P < 0.001) and a significant elevation in total thiol concentration, as compared with PTZ group (P < 0.05 and P < 0.01). The present study showed that the hydroalcoholic extract of A. wilhelmsii possesses an antioxidant effect in the brain in PTZ induced seizure model.

Protective effects of cinnamon on acetylcholinesterase activity and memory dysfunction in diabetic rats.

OBJECTIVES: Regarding neurocognitive and immunomodulatory properties of cinnamon (Cinn) we aimed to investigate whether cinnamon regulates acetylcholinesterase (AChE) activity, and oxidative abnormalities with concomitant memory dysfunction in streptozotocin (STZ)-induced diabetes. METHODS: Forty-seven male adult rats were divided into seven groups (n=8 animals): Control group: in these non-diabetic rats only saline 0.9% NaCl was gavaged, Diabetic (Dia) group: diabetic rats in them saline 0.9% NaCl was gavaged for six weeks. Dia-Cinn 100, Dia-Cinn 200, and Dia-Cinn 400, Dia-Met groups: in these diabetic rats the extract (100, 200, 400 mg/kg respectively) or metformin (300 mg/kg) was gavaged for six weeks. Passive avoidance performance, AChE enzyme activity, and oxidative indicators were examined among the groups. RESULTS: Vs. the control group, blood glucose level and stay time in the dark were remarkably increased in Dia group whereas the latency time was decreased. Meanwhile, antioxidant levels (superoxide dismutase, catalase, and thiols) noticeably decreased in the Dia group compared to the Control group. On the other hand, Cinn extract espicailly at the highest dose recovered the changes similar to those found in the metformin-treated group. CONCLUSIONS: These findings proposed that the cinnamon hydro-ethanolic extract promotes memory recovery in diabetic conditions through the atteuation of the AChE activity and oxidative injury.

The effects of endurance exercise and metformin on memory impairment caused by diabetes.

OBJECTIVES: Diabetes has a negative effect on learning and memory performance, and it is a risk factor for Alzheimer's disease and dementia development. The present study aims to investigate the effects of two kinds of endurance exercise including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) as well as metformin on impaired memory and learning related to streptozotocin (STZ) induced diabetes in rats. METHODS: Forty adult male rats (250 ± 20 g weight) were divided into five groups (n=8), including control, diabetic, as well as diabetic rats treated with metformin (300 mg/kg), and HIIT (20 m/min), and MICT (15 m/min) exercises. Diabetes was induced by STZ (60 mg/kg, i.p.). Serum glucose concentration and oxidative stress markers (SOD, CAT, thiol, and MDA) in the cortex and hippocampus were determined by colorimetric assay. Behavioral tests were performed with a passive avoidance test. RESULTS: The diabetic groups treated with metformin and both HIIT, and MICT exercises improved the latency and the staying time in the darkroom and lightroom. The entrance frequency into the darkroom also was restored (p<0.01-p<0.001). In both HIIT and MICT exercises as well as metformin groups the oxidative stress induced by diabetes has been reversed and attenuation of the serum glucose level has been observed compared to non-treated diabetic ones (p<0.05-p<0.001). CONCLUSIONS: The results of the present study revealed both HIIT and MICT exercises had protective effects against oxidative stress and behavioral impairments induced by diabetes and these effects were comparable to the effects of metformin.

The effects of vitamin D on cardiovascular damage induced by lipopolysaccharides in rats.

Introduction: Inflammation and oxidative stress are contributed to cardiovascular diseases. Vitamin D (Vit D) has antioxidant and anti-inflammatory properties. In the current research, the effect of Vit D on cardiac fibrosis and inflammation, and oxidative stress indicators in cardiovascular tissues was studied in lipopolysaccharides(LPS) injected rats. Methods: Rats were distributed into 5 groups and were treated for 2 weeks. Control: received vehicle(saline supplemented with tween-80) instead of Vit D and saline instead of LPS, LPS: treated by 1 mg/kg of LPS and was given vehicle instead of Vit D, LPS-Vit D groups: received 3 doses of Vit D (100, 1000, and 10000 IU/kg) of Vit D in addition to LPS. Vit D was dissolved in saline supplemented with tween-80 (final concentration 0.1%) and LPS was dissolved in saline. The white blood cell (WBC) was counted. Oxidative stress markers were determined in serum, aorta, and heart. Cardiac tissue fibrosis was also estimated using Masson's trichrome staining method. Results: WBC and malondialdehyde (MDA) were higher in the LPS group than the control group, whereas the thiol content, superoxide dismutase (SOD), and catalase (CAT) were lower in the LPS group than the control group (P<0.01 and P<0.001). Administration of Vit D decreased WBC (P<0.001) and MDA (P<0.05 and P<0.001) while enhanced thiol (dose 10000 IU/Kg) (P<0.001), SOD (dose 10000 IU/kg) (P<0.001), and CAT (P<0.05 and P<0.001) compared to the LPS group. All doses of Vit D also decreased cardiac fibrosis compared to the LPS group (P<0.001). Conclusion: Vit D protected the cardiovascular against the detrimental effect of LPS. This cardiovascular protection can be attributed to the antioxidant and anti-inflammatory properties of Vit D.

Anti-inflammatory, anti-oxidant and anti-apoptotic effects of olive leaf extract in cardiac tissue of diabetic rats.

OBJECTIVES: Inflammatory process and apoptosis are involved in the pathogenesis of cardiac injury and oxidative damage caused by diabetes mellitus. The cardioprotective effects of standardized aqueous ethanolic olive leaf extract (OLE), metformin (as a cardiovascular protective agent) and valsartan (as an angiotensin receptor blocker) in the streptozotocin-induced diabetic rats were evaluated. METHODS: Wistar rats divided into control, diabetic, OLE-treated (100, 200 and 400 mg/kg), metformin (300 mg/kg)-treated, valsartan (30 mg/kg)-treated and metformin/valsartan-treated diabetic groups. Biochemical parameters, including malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activates, and the total contents of thiol were measured, and histopathological and gene expression studies were done on cardiac tissues. Fasting blood sugar (FBS) and cardiac injury markers were examined in serum. KEY FINDINGS: FBS; the serum levels of lactate dehydrogenase (LDH), creatine kinase-muscle/brain (CK-MB), aspartate aminotransferase (AST); and heart tissue MDA levels due to diabetes were significantly alleviated by OLE treatment (effect size; ηp2 = 0.934, 0.888, 0.848, 0.888 and 0.879, respectively), and SOD and CAT activity and the thiol content in heart tissue were significantly increased (effect size; ηp2 = 0.770, 0.749 and 0.753, respectively). Interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α) and the number of infiltrating inflammatory cells were reduced in cardiac tissues of OLE-treated groups compared with the diabetic rats (effect size; ηp2 = 0.969 and 0.949, respectively). OLE up-regulated BCL2 gene expression and down-regulated BAX gene expression in cardiac tissue (effect size; ηp2= 0.490 and 0.522, respectively). CONCLUSION: OLE in a dose-dependent manner ameliorates cardiac damage in diabetic cardiomyopathy, perhaps through attenuating inflammation, oxidative stress and apoptosis.

Diabetic cardiomyopathy was attenuated by cinnamon treatment through the inhibition of fibro-inflammatory response and ventricular hypertrophy in diabetic rats.

Diabetic cardiomyopathy (DCM) is a chronic complication of diabetes that emphasizes the urgency of developing new drug therapies. With an illustrious history in traditional medicine to improve diabetes, cinnamon has been shown to possess blood lipids lowering effects and antioxidative and anti-inflammatory properties. However, the extent to which it protects the diabetic heart has yet to be determined. Forty-eight rats were administered in the study and grouped as: control; diabetic; diabetic rats given 100, 200, or 400 mg/kg cinnamon extract, metformin (300 mg/kg), valsartan (30 mg/kg), or met/val (combination of both drugs), via gavage for six weeks. Fasting blood sugar (FBS) and markers of cardiac injury including creatine kinase-muscle/brain (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were evaluated in blood samples. Malondialdehyde (MDA) levels, the total contents of thiol, superoxide dismutase (SOD), and catalase (CAT) activities were measured. Histopathology study and gene expression measurement of angiotensin II type 1 receptor (AT1), atrial natriuretic peptide (ANP), beta-myosin heavy chain (ß-MHC), and brain natriuretic peptide (BNP) were done on cardiac tissue. FBS and cardiac enzyme indicators were reduced in all treated groups. A reduction in MDA level and enhancement in thiol content alongside with increase of SOD and CAT activities were observed in extract groups. The decrease of inflammation and fibrosis was obvious in treated groups, notably in the high-dose extract group. Furthermore, all treated diabetic groups showed a lowering trend in AT1, ANP, ß-MHC, and BNP gene expression. Cinnamon extract, in addition to its hypoglycemic and antioxidant properties, can prevent diabetic heart damage by alleviating cardiac inflammation and fibrosis. PRACTICAL APPLICATIONS: This study found that cinnamon extract might protect diabetic heart damage by reducing inflammation and fibrosis in cardiac tissue, in addition to lowering blood glucose levels and increasing antioxidant activity. Our data imply that including cinnamon in diabetic participants' diets may help to reduce risk factors of cardiovascular diseases.

Olea europaea L. (olive) leaf extract ameliorates learning and memory deficits in streptozotocin-induced diabetic rats.

Objective: The aim of the present study was to assess olive leaf extract (OLE) effects on learning and memory deficits in a model of diabetes induced by streptozotocin (STZ) in rats. Materials and methods: The rats were divided as: (1) control rats, (2) diabetic rats, and (3-6) diabetic rats treated by 100, 200, and 400 mg/kg of OLE or metformin. Using the passive avoidance test (PA), we investigated fear learning and memory behaviors. In cortical and hippocampus tissues, total levels of malondialdehyde (MDA) and thiol were measured along with the activity of catalase (CAT) and superoxide dismutase (SOD). Results: Learning and memory behavior impairment were significantly developed in diabetic rats as shown by the impairment of the PA task compared to the control group (p<0.001). In addition, elevated levels of MDA and reduced overall concentrations of thiol, CAT and SOD activity were obvious in diabetic rats' cortex and hippocampus tissues (p<0.01-p<0.001). Meanwhile, OLE in a dose-dependent manner, improved memory deficit and cognitive performance that was attributed to a reduction of lipid peroxidation and elevation of total thiol concentration, and CAT and SOD activity levels in the brain tissues (p<0.05-p<0.001). Conclusion: OLE could be effective in improving cognitive impairment in STZ-induced diabetes by oxidative stress depression.

Cardiac hypertrophy and fibrosis were attenuated by olive leaf extract treatment in a rat model of diabetes.

The key role of fibrosis and hypertrophy processes in developing diabetes-induced heart injury has been demonstrated. Considering the known hypoglycemic effects of olive leaf extract (OLE), we decided to investigate its potential effect and associated mechanisms on cardiac fibrosis and myocardial hypertrophy in streptozotocin (STZ)-induced diabetic rats. Eight groups were included in this study: control, diabetic, diabetic-OLEs (100, 200 and 400 mg/kg), diabetic-metformin (300 mg/kg), diabetic-valsartan (30 mg/kg), and diabetic-metformin/valsartan (300/30 mg/kg). After a treatment period of 6 weeks, echocardiography was used to assess cardiac function. Heart-to-body weight ratio (HW/BW) and fasting blood sugar (FBS) were measured. Myocardial histology was examined by Masson's trichrome staining. Gene expressions of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), ß-myosin heavy chain (ß-MHC), TGF-ß1, TGF-ß3, angiotensin II type 1 receptor (AT1), alpha-smooth muscle actin (α-SMA), and collagen were evaluated by the quantitative real-time PCR in heart tissue. A reduction in the FBS level and HW/BW ratio in the extract groups was obvious. The improvement of left ventricular dysfunction, cardiac myocytes hypertrophy, and myocardial interstitial fibrosis was also observed in treated groups. A lowering trend in the expression of all hypertrophic and fibrotic indicator genes was evident in the myocardium of OLE treated rats. Our data indicated that OLE could attenuate fibrosis and reduce myocardial hypertrophy markers, thus improving the cardiac function and structure in the STZ-induced diabetic rats. PRACTICAL APPLICATIONS: This study demonstrates that olive leaf extract in addition to lowering blood glucose levels and the heart-to-body weight ratio (HW/BW) may also improve cardiac function and reduce cardiac hypertrophy and fibrosis in cardiac tissue, which leads to inhibition of diabetic heart damage. Thus it is possible that including olive leaf extracts in the diets of individuals with diabetes may assist in lowering cardiovascular disease risk factors.

Protective effects of medicinal plant against diabetes induced cardiac disorder: A review.

ETHNOPHARMACOLOGY RELEVANCE: Nowadays, there is an increase in global tendency to use medicinal plants as preventive and therapeutic agents to manage diabetes and its long-term complications such as cardiovascular disorders owing to their availability and valuable traditional background. AIM OF STUDY: This review aims to introduce common medicinal plants, which have been demonstrated to have cardioprotective effects on diabetes and their mechanisms of action. MATERIALS AND METHODS: Online literature databases, including Web of Sciences, PubMed, Science Direct, Scopus and Google Scholar were searched without date limitation by May 2020. The following keywords (natural products or medicinal plants or herbal medicine or herb or extract) and (diabetes or antidiabetic or hyperglycemic) and (cardiomyopathy or heart or cardioprotective or cardiac or cardio) were used, and after excluding non-relevant articles, 81 original English articles were selected. RESULTS: The surveyed medicinal plants induced cardioprotective effects mostly through increasing antioxidant effects leading to attenuating ROS production as well as by inhibiting inflammatory signaling pathways and related cytokines. Moreover, they ameliorated the Na+/K + ATPase pump, the L-type Ca2+ channel current, and the intracellular ATP. They also reduced cardiac remodeling and myocardial cell apoptosis through degradation of caspase-3, Bax, P53 protein, enhancement of Bcl-2 protein expression as well as downregulation of TGFß1 and TNFα expression. In addition, the extracts improved cardiac function through increasing EF% and FS% as well as restoring hemodynamic parameters. CONCLUSIONS: The reviewed medicinal plants demonstrated cardioprotective manifestations in diabetes through intervention with mechanisms involved in the diabetic heart to restore cardiovascular complications.

Cardioprotective effects of Fenugreek (Trigonella foenum-graceum) seed extract in streptozotocin induced diabetic rats.

Introduction: Inadequate control of diabetes mellitus (DM) leads to considerable cardiovascular implications like diabetic cardiomyopathy (DCM). Cardiomyocyte apoptosis is one of the main mechanisms of DCM pathogenesis associated with hyperglycemia, oxidative stress, inflammation, hyperlipidemia and several other factors. Trigonella foenum-graecum (Fenugreek) has been long used as a traditional medicine and has many therapeutic effects, including anti-diabetic, anti-hyperlipidemia, anti-inflammatory and anti-oxidant properties. The current study aimed to investigate cardioprotective effects of fenugreek seed on diabetic rats. Methods: Diabetes was induced in forty-two male rats by injection of streptozotocin (STZ) (60 mg/ kg). Diabetic animals were treated with three different doses of fenugreek seed extract (50, 100 and 200 mg/kg) or metformin (300 mg/kg) for six weeks by gavage. Nondiabetic rats served as controls. Glucose, cholesterol, and triglycerides levels were measured in the blood samples, and oxidative stress markers as well as gene expression of ICAM1 , Bax and Bcl2 were assessed in the cardiac tissues of the experimental groups. Results: Diabetic rats exhibited increased serum glucose, cholesterol and triglycerides levels, elevated markers of oxidative stress thiobarbituric acid-reacting substances (TBARS) levels , total thiol groups (SH), catalase (CAT) and superoxide dismutase (SOD) activity, and enhanced apoptosis cell death (ratio of Bax/Bcl2). Fenugreek seed extract considerably improved metabolism abnormalities, attenuated oxidative stress and diminished apoptosis index. Conclusion: Our study suggests that fenugreek seed may protect the cardiac structure in STZ-induced diabetic rats by attenuating oxidative stress and apoptosis.

The vasodilatory effect of Apium graveolens L (celery) seed in isolated rat aorta: The roles of endothelium, calcium and potassium channels.

OBJECTIVE: Apium graveolens L. (celery) seed has been used for hypertension treatment. To provide a pharmacological basis, the vasorelaxant effect of celery seed extract was investigated in isolated rat aorta. MATERIALS AND METHODS: Wistar male rats (200-250 g) were divided into 15 groups (n=7 for each group). The vasorelaxant response of different concentrations of celery seed extract (0.05, 0.1, 0.25, 0.5, 1, and 2 mg/ml) on isolated aorta precontracted with phenylephrine (PE) or KCl was evaluated by organ bath technique. The role of endothelium, extracellular calcium influx, intracellular sources of calcium, and potassium channels in vasorelaxant effect of celery seed extract was investigated. RESULTS: The extract showed a concentration-dependent relaxation in the isolated aorta contracted with PE and KCl that was endothelium-dependent at lower concentrations. Pretreatment of aortic rings with indomethacin or L-NAME, did not affect the vasorelaxation induced by celery seed extract. The extract inhibited KCl and PE-induced contractions in cumulative calcium concentrations as well as after incubation with diltiazem in denuded aortic rings of endothelium. The relaxation induced by celery seed extract was inhibited by 4-aminopyridine. CONCLUSION: This relaxation was mediated by inhibiting calcium influx into vascular smooth muscle cells. Also, voltage-dependent potassium channels were involved in inducing the vasorelaxant effect of celery seed extract.

Ginger (Zingiber Officinale Roscoe) Extract Protects the Heart Against Inflammation and Fibrosis in Diabetic Rats.

BACKGROUND: Fibrosis and inflammation in the heart of patients with diabetes mellitus alongside increased production of free radicals and collagen are together known as diabetic cardiomyopathy. Ginger rhizome has antidiabetic, antioxidant and anti-inflammatory effects. Thus, we investigated the effect of ginger extract on diabetes-induced cardiomyopathy in streptozotocin-induced diabetic rats. METHODS: Animals were divided into 7 groups: control; diabetic; diabetic treated with different doses of ginger extract of 100, 200 and 400 mg/kg; metformin (200 mg/kg); and metformin-valsartan (200 and 30 mg/kg, respectively). Serum levels of glucose, aspartate aminotransferase, lactate dehydrogenase and creatine kinase-muscle/brain were measured. Fibrosis and inflammation were determined by histologic assessment. Gene expression of transforming growth factor (TGF)-ß1, TGF-ß3 and angiotensin II type 1 receptor was evaluated by real-time polymerase chain reaction in heart tissue. RESULTS: Serum glucose level in all treated groups, except for the ginger extract 100-mg/kg group, was significantly lower than in the diabetic group. Serum levels of aspartate aminotransferase, lactate dehydrogenase and creatine kinase-muscle/brain were significantly reduced in all treated groups compared with the diabetic group. In the study of fibrosis, collagen amount in the heart tissue of all treated groups, except the ginger extract 100-mg/kg group, was significantly lower than in the diabetic group. Inflammatory cell infiltrates were decreased, and disarrangement was improved in cardiac tissues of all treated groups compared with the diabetic group. Expression of angiotensin II type 1 receptor and TGF-ß1 and TGF-ß3 genes in all treated groups downregulated compared with the diabetic group. CONCLUSIONS: Treatment by ginger extract reduced myocardial fibrosis and inflammation in the course of diabetic cardiomyopathy, possibly through regulation of the expression of genes involved in the SMAD/TGF-ß pathway.

Zingiber officinale (Ginger) hydroalcoholic extract improved avoidance memory in rat model of streptozotocin-induced diabetes by regulating brain oxidative stress.

OBJECTIVES: Diabetes mellitus associated cognitive impairment is suggested to be due to oxidative stress. Considering the anti-diabetic, antioxidant, antihyperlipidemic, and anti-inflammatory effects of Zingiber officinale, the present study aimed to investigate its effect on memory and oxidative stress factors in streptozotocin (STZ)-induced diabetic rats. METHODS: The rats were allocated into five groups: Control, Diabetic, Diabetic + Ginger 100, Diabetic + Ginger 200, and Diabetic + Ginger 400. Following diabetes induction by STZ (60 mg/kg), 100, 200, or 400 mg/kg Ginger was given for eight weeks. Passive avoidance test (PA) was done and thiol, malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) measurements were carried out in the brain. RESULTS: The latency into the dark compartment decreased (p<0.001) and the number of entries and time spent in the dark chamber increased in the Diabetic group compared to the Control (p<0.001 for all). All three doses of extract improved performance of the rats in the PA test (p<0.001 for all). The hippocampal and cortical MDA level was higher (p<0.001) while CAT, SOD, and total thiol were lower (p<0.01-p<0.001) in the Diabetic group than the Control. Treatment with 200 and 400 mg/kg Z. officinale extract reduced hippocampal and cortical MDA (p<0.001) and improved CAT (p<0.001) while, just the dose of 400 mg/kg of the extract increased SOD and total thiol in hippocampal and cortical tissues (p<0.001) compared with Diabetic group. CONCLUSIONS: Z. officinale extract could improve memory by reducing the oxidative stress in STZ-induced diabetes model.

Effects of prolactin on movement disorders and APOE, GFAP, and PRL receptor gene expression following intracerebral hemorrhage in rats.

Objectives: Intracerebral hemorrhage (ICH) occurs mostly in the striatum. In ICH, blood prolactin level increases 3-fold. The effects of intracerebroventricular injection (ICV) of prolactin on motor disorders will be investigated. Materials and Methods: This study was performed on 32 male Wistar rats in 4 groups: sham, ICH, and prolactin with 1 µg/2 µl (P1) and 2 µg/2 µl (P2) doses. Results: The weight of animals on days 1 (P˂0.01), 3, and 7 (P˂0.05) in the sham and P2 groups increased compared with the ICH group. Neurological Deficit Score (NDS) in ICH and P1 groups decreased, and increased compared with sham and ICH groups (P˂0.001), respectively. NDS in the P1 group increased compared with the P2 group on days 1 (P˂0.0 5), 3, and 7 (P˂0.001). The duration time of rotarod in ICH and P1 groups decreased and increased compared with sham and ICH groups (P˂0.001), respectively. The duration time of rotarod in the P1 group on days 3 and 7 increased compared with the P2 group (P˂0.001). Travel distance in days 1(P˂0.01), 3(P˂0.001), and 7(P˂0.01) decreased in the ICH group. Prolactin receptor (PRL receptor) expression in ICH, P1, and P2 groups increased compared with sham and ICH groups (P˂0.001). Glial fibrillary acidic protein (GFAP) expression (P˂0.001) and apolipoprotein E (APOE) (P˂0.01) expression in the ICH group increased compared with the sham group. GFAP and APOE expression in the P1 group increased compared with the ICH group (P˂0.001). APOE expression in the P1 group increased compared with the P2 group (P˂0.001). Conclusion: According to the results, prolactin reduces movement disorders.

Ventricular-arterial uncoupling in heart failure with preserved ejection fraction after myocardial infarction in dogs - invasive versus echocardiographic evaluation.

BACKGROUND: Heart failure with preserved left ventricular ejection fraction and abnormal diastolic function is commonly observed after recovery from an acute myocardial infarction. The aim of this study was to investigate the physiopathology of heart failure with preserved ejection fraction in a model of healed myocardial infarction in dogs. METHODS: Echocardiography, levels of neurohormones and conductance catheter measurements of left ventricular pressure-volume relationships were obtained in 17 beagle dogs 2 months after a coronary artery ligation, and in 6 controls. RESULTS: Healed myocardial infarction was associated with preserved echocardiographic left ventricular ejection fraction (0.57 +/- 0.01, mean +/- SEM) and altered Doppler mitral indices of diastolic function. NT-proBNP was increased, aldosterone was decreased, and norepinephrine was unchanged. Invasive measurements showed a markedly decreased end-systolic elastance (2.1 +/- 0.2 vs 6.1 +/- 0.8, mmHg/ml, p < 0.001) and end-systolic elastance to effective arterial elastance ratio (0.6 +/- 0.1 vs 1.4 +/- 0.2, p < 0.001), with altered active relaxation (dP/dtmin -1992 +/- 71 vs -2821 +/- 305, mmHg/s, p < 0.01) but preserved left ventricular capacitance (70 +/- 6 vs 61 +/- 3, ml at 20 mmHg, p = NS) and stiffness constant. Among echocardiographic variables, the wall motion score index was the most reliable indicator of cardiac contractility while E', E/A and E'/A' were correlated to dP/dtmin. CONCLUSIONS: In the canine model of healed myocardial infarction induced by coronary ligation, heart failure is essentially characterized by an altered contractility with left ventricular-arterial uncoupling despite vascular compensation rather than by abnormal diastolic function.