Effect of Mucuna pruriens on brain NMDA receptor and tau protein gene expression in cerebral ischemic rats.

Present study aimed to assess effect of pre-treatment with Mucuna pruriens seed extract and its bioactive molecule(s) on NMDAR and Tau protein gene expression in cerebral ischemic rodent model. Methanol extract of M. pruriens seeds was characterized by HPLC, and ß-sitosterol was isolated by flash chromatography. In vivo studies to observe the effect of pre-treatment (28 days) with methanol extract of M. pruriens seed and ß-sitosterol on the unilateral cerebral ischemic rat model. Cerebral ischemia induced by left common carotid artery occlusion (LCCAO) for 75 min (on day 29) followed by reperfusion for 12 h. Rats (n = 48) divided into four groups. GroupI (control,Untreated + LCCAO)-No pre-treatment + cerebral ischemia; GroupII(ß-sitosterol + Sham)-pre-treatment with ß-sitosterol, 10 mg/kg/day + sham-operated; GroupIII(ß-sitosterol + LCCAO)-pre-treatment with ß-sitosterol, 10 mg/kg/day + cerebral ischemia; GroupIV(methanol extract + LCCAO)-pre-treatment with methanol extract of M. pruriens seeds, 50 mg/kg/day + cerebral ischemia. Neurological deficit score was assessed just before sacrifice. Experimental animals were sacrificed after 12 h reperfusion. Brain histopathology was performed. Gene expression of NMDAR and Tau protein of left cerebral hemisphere (occluded side) was performed by RT-PCR. Results revealed that the neurological deficit score was lower in groups III and IV compared to group I. NMDAR and tau protein mRNA expression in left cerebral hemisphere were upregulated in Group I, downregulated in groups III and IV. Histopathology of left cerebral hemisphere (occluded side) in Group I showed features of ischemic brain damage. Groups III and IV, left cerebral hemisphere showed less ischemic damage compared GroupI. Right cerebral hemisphere showed no areas of ischemia-induced brain changes. Pre-treatment with ß-sitosterol and methanol extract of M. pruriens seeds may reduce ischemic brain injury following unilateral common carotid artery occlusion in rats.

Structural analysis and prediction of potent bioactive molecule for eNOS protein through molecular docking.

Reactive oxygen species by uncoupled eNOS is linked to endothelial dysfunction. Ellagic acid (EA), a polyphenol possesses numerous biological activities including radical scavenging. whether EA exerts a vasculo-protective effect via antioxidant mechanisms in blood vessels remains unknown. Molecular docking provides an initial model of protein and molecular interactions in various physiological and/or pathological functions. To identify a eNOS modulatory biomolecule through molecular docking as possible vascular protective agent. On the basis of binding affinities and other physicochemical features, a molecular docking-based approach was used to classify and evaluate eNOS binding micronutrients found in natural sources, Lipinski's rule was used taking into account their adsorption, delivery, metabolism, and excretion (ADME). An insilico approach focused on the ligand-protein interaction technique to determine the therapeutic potential of certain phytochemical-based drugs for the vascular remodelling.20 bioactive molecules were screened, docking analysis on human eNOS proteins was performed. The best poses for target protein was established based on binding energy and inhibition constant. EA and caffeine acid are the strongest candidates for eNOS protein functional norms. This provides a novel insight into the interaction properties of known human eNOS protein with EA and used as a therapeutic agent in various pathologies. Predicting interaction of ellagic acid with eNOS protein by molecular docking in endothelial dysfunction.

Terminalia arjuna supplementation ameliorates high fat diet-induced oxidative stress in nephrotoxic rats.

OBJECTIVES: Dietary high fat possibly causes oxidative stress; also it makes deleterious effect on kidney functions and land up in lipotoxicity in renal tissue. Lipotoxicity is the pathological situation where lipid Peroxidation occurs and generates reactive oxygen species (ROS). Overproduction of ROS than antioxidant present in tissues cause oxidative stress. Terminalia arjuna is found to be potential antioxidant that counteract oxidative stress and possibly maintain glomerular integrity. METHODS: Ethanolic extract of T. arjuna (ETO) was prepared and phytochemical analysis was done. Rats were divided into four groups, having six rats in each group as following; group 1-Control (20% fat); group 2 (ETO 100 mg/kg/b.wt); group 3 (30% fat) and group 4 (30% fat + ETO 100 mg/kg/b.wt). Dietary and ETO supplementation were continued for 21 days. Gravimetric, kidney functions (blood urea and serum creatinine) and oxidative stress markers like MDA, SOD and GSH were evaluated. Histopathological analysis was done on kidney along with measurement of glomerular integrity. Morphometrical analysis of glomerular integrity was evaluated by measuring glomerular length, width, glomerular area and Bowman's capsule radius. One way ANOVA was done for analysis of data. RESULTS: Blood urea and serum creatinine levels were significantly higher in high fat fed rats indicating renal dysfunction. High fat diet showed significant increase in MDA, decrease in SOD and GSH in rats fed with high fat diet, which indicate generation of oxidative stress. Supplementation of ETO showed amelioratic effect against high fat diet induced renal dysfunction and oxidative stress. Histopathological findings were significantly corroborated with morphometrical analysis of glomerular integrity. CONCLUSIONS: Ethanolic extracts of T. arjuna supplementation found to be beneficial against high fat induced renal alterations in terms of functions and architecture.

Low oxygen microenvironment and cardiovascular remodeling: Role of dual L/N.type Ca2+ channel blocker.

OBJECTIVE: Patients exposed to chronic sustained hypoxia frequently develop cardiovascular disease risk factors to ultimately succumb to adverse cardiovascular events. In this context, the present study intends to assess the role of cilnidipine (Cil), a unique calcium channel blocker that blocks both L-type and N-type calcium channels, on cardiovascular pathophysiology in face of chronic sustained hypoxia exposure. MATERIALS AND METHODS: The study involved Wistar strain albino rats. The group-wise allocation of the experimental animals is as follows - Group 1, control (21% O2); Group 2, chronic hypoxia (CH) (10% O2, 90% N); Group 3, Cil + 21% O2; and Group 4, CH (10% O2, 90% N) + Cil (CH + Cil). Cardiovascular hemodynamics, heart rate variability, and endothelial functions (serum nitric oxide [NO], serum endothelial nitric oxide synthase [NOS3], and serum vascular endothelial growth factor [VEGF]) were assessed. Cardiovascular remodeling was studied by histopathological examination of the ventricular tissues, coronary artery (intramyocardial), and elastic and muscular arteries. Normalized wall index of the coronary artery was also calculated. RESULTS AND CONCLUSION: The results demonstrated altered cardiovascular hemodynamics, disturbed cardiovascular autonomic balance, increased levels of VEGF and NOS3, and decreased bioavailability of NO on exposure to chronic sustained hypoxia. The histopathological examination further pointed toward cardiovascular remodeling. Treatment with Cil ameliorated the cardiovascular remodeling and endothelial dysfunction induced by CH exposure, which may be due to its blocking actions on L/N-type of calcium channels, indicating the possible therapeutic role of Cil against CH-induced cardiovascular pathophysiology.

Emblica officinalis (Amla) Ameliorates High-Fat Diet Induced Alteration of Cardiovascular Pathophysiology.

BACKGROUND: Dietary high fat possibly causes oxidative stress. Also, it alters the pathophysiology of metabolically active myocardial tissues and vascular architecture. Emblica officinalis contains a potential antioxidant that counteracts oxidative stress and possibly maintains vascular integrity. OBJECTIVES: To assess the effect of ethanolic extract of Emblica officinalis (EEO) on High Fat Diet (HFD) induced changes in vascular chemistry and histopathology of the cardiovascular system in male albino rats. MATERIALS AND METHODS: Ethanolic extract of Emblica officinalis (EEO) was prepared and phytochemical analysis was done. Rats were divided into four groups, having six rats in each group as follows: group 1- Control (20% fat); group 2 (20% fat+ EEO 100 mg/kg/b w); group 3 (30% fat) and group 4 (30% fat + EEO 100 mg/kg/b w). Dietary and EEO supplementation was continued for 21 days. Gravimetric and oxidative stress markers like MDA, NO, antioxidants like Vitamin C and E, and molecular marker (NOS3) were evaluated. Histopathological analysis was done on the myocardium and elastic artery along with measurement of coronary arterial wall thickness and lumen diameter. One way ANOVA was done for analysis of data. RESULTS: High fat diet showed a significant increase in MDA, decrease of NO with unaltered NOS3 protein in rats fed with high fat diet, which indicate possible alteration of vascular pathophysiology. Supplementation of EEO showed an ameliorating effect on high fat diet induced oxidative stress. These results were further corroborated with findings of a histopathological study on the myocardium, elastic artery and coronary arterial architecture. CONCLUSION: Ethanolic extract of Emblica officinalis (EEO) indicates its cardioprotective efficacy against rats fed with high fat diet.

Subchronic hypoxia pretreatment on brain pathophysiology in unilateral common carotid artery occluded albino rats.

OBJECTIVE: This study was aimed to assess the effect of unilateral common carotid artery occlusion on brain pathophysiology in rats pretreated with subchronic hypoxia. MATERIALS AND METHODS: Rats (200 ± 20 g) were randomized into three groups: Group 1 served as sham, Group 2 were normoxic (21% O2 and 79% N2), and Group 3 were hypoxia preconditioned (10% O2 and 90% N2) for 21 days before left common carotid artery occlusion (LCCAO). The LCCAO was done for 75 min followed by reperfusion for 12 h. Neurological scores were recorded. Serum malondialdehyde (MDA) and nitric oxide (NO) levels at pre- and 12 h post-LCCAO were measured. Brain histopathological assessments were also done. RESULTS: Higher neurological deficits scores in Group 2 as compared to Group 3 rats were noticed. Serum MDA and NO levels at 12 h post-LCCAO in Group 2 rats showed significant elevation as compared to preocclusion levels. Group 3 rats did not show such elevations. On histopathology of left and right cerebral hemispheres of Group 1 (sham) did not show any specific changes. In Group 2 rats, the right cerebral hemisphere (nonoccluded) showed no areas of ischemia-induced brain changes, but in the left side (occlusive), there were features of ischemic brain damage including cerebral edema. In the case of Group 3 rats, there were less ischemic damages in the left occluded side as compared to the left side of the Group 2 rats. CONCLUSION: This study clearly demonstrates that subchronic hypoxia pretreatment can reduce ischemic brain injury by unilateral common carotid artery occlusion in rats.

Protective effects of Ethanolic Extract of Emblica officinalis (amla) on Cardiovascular Pathophysiology of Rats, Fed with High Fat Diet.

INTRODUCTION: Dietary high fat alters lipid profile and possibly induce sympatho-vagal imbalance. Emblica officinalis is found to be potential antioxidant and possibly counteract hyperlipidemia induced lipid peroxidation. AIM: To assess Ethanolic extract of Emblica Officinalis (EEO) as lipid lowering and cardiovascular protective agent against high dietary fat supplemented to experimental rats. Further to study a comparative analysis between EEO and atorvastatin on hyperlipidemia and cardiovascular integrity. MATERIALS AND METHODS: EEO was prepared and phytochemical analysis was done. Rats were divided into five groups, having six rats in each group as following; Group I-control (20% fat); Group II (+ EEO 100 mg/kg body wt); Group III (fed with high fat diet; 30% fat); Group IV (fed with high fat diet; 30% fat + EEO 100 mg/kg body wt) and Group V (fed with high fat diet; 30% fat + atorvastatin 4 mg/kg body wt). The treatments were continued for 21 days. Gravimetric parameters and electrophysiological parameters {Heart Rate (HR), sympatho-vagal balance} were recorded and lipid profiles of all the groups were measured. ANOVA, correlation and multiple regressions were done for analysis of data. RESULTS: Significant alteration in serum lipid profile was observed in rats fed with high dietary fat but supplementation of EEO was found to be reversible. Electrophysiological evaluation revealed altered HR and sympatho-vagal balance in high dietary fat fed rats (Group III) which indicate cardiac autonomic malfunctions which were found to be improved in Emblica officinalis supplemented group of rats (Group IV). Further, analysis has shown significant negative correlation between HDL/LDL and sympatho-vagal balance in all groups of rats which clearly indicate a role of dietary fat on sympatho-vagal balance. These results further corroborated with findings of histopathological study on myocardium and elastic artery. CONCLUSION: Observations from the study indicate a beneficial role of ethanolic extract of Emblica officinalis (amla) on dyslipidemia and cardiac autonomic functions in rats treated with high fat diet.

Effects of Some Indigenous Plants of North Karnataka (India) on Cardiovascular and Glucose Regulatory Systems in Alloxan-Induced Diabetic Rats.

BACKGROUND: Kenaf (Hibiscus cannabinus Linn, Pundi), Chick pea (Cicer arietinum Linn, Chana) and Prickly lettuce (Lactuca scariola Linn, Hattaraki) leaves are a few of indigenous plants which are routinely consumed by the people of north Karnataka in the diet. Studies on these plants showed some potential anti-diabetic efficacies. OBJECTIVES: To examine the effect of leaves extracts of Hibiscus cannabinus Linn, Cicer arietinum Linn and Lactuca scariola Linn on cardiovascular integrity, glucose homeostasis and oxygen sensing cell signaling mechanisms in alloxan induced diabetic rats. METHOD: In vitro and in vivo tests on glucose regulatory systems and molecular markers such as - NOS3, HIF- 1α and VEGF were conducted in alloxan induced diabetic rats supplemented with all the three plant extracts. Electrophysiological analysis (HRV, LF: HF ratio, baroreflex sensitivity, BRS) and histopathogy of myocardial tissues and elastic artery were evaluated in diabetic rats treated with L. scariola linn. RESULTS: Out of these three plant extracts, Lactuca scariola Linn supplementation showed significant beneficial effects on glucose homeostasis and oxygen sensing cell signaling pathways in alloxaninduced diabetic rats. Furthermore, effects of sub chronic supplementation of Lactuca scariola Linn aqueous extracts showed significant improvement in sympatho-vagal balance in diabetic rats by increase of Heart Rate Variability (HRV) and regaining of Baroreflex Sensitivity (BRS). These results were also corroborated with myocardial and elastic artery histopathology of Lactuca scariola Linn supplemented diabetic rats. CONCLUSION: These findings indicate an adaptive pathway for glucose homeostasis, oxygen sensing cell signaling mechanisms and cardio protective actions in alloxan - induced diabetic rats supplemented with Lactuca scariola Linn extracts.

Different anthropometric adiposity measures and their association with cardiovascular disease risk factors in middle aged women.

A cross sectional study of 136 women age group40-55 years was conducted to study which anthropometric measure had the strongest association with cardiovascular disease risk factors in middle aged women. In accordance with their BMI measurement subjects were divided into three groups namely: Normal weight (Group1) BMI 18.5-24.9 kg/m2, Overweight (Group2) - 25 kg/m2 - 29.9 kg/m2, Obese (Group3) - BMI > 30 kg/m2. Each group was further divided into premenopausal and postmenopausal women BMI, WHR, WHtR, SBP, DBP were recorded. TG, TC, HDL and FBS values were estimated. Results showed that both pre and post menopausal middle aged obese women with higher BMI, WHR and WHtR have more chances of having cardiovascular diseases. BMI, WHR and WHtR are theeasy and practical methods to diagnose obesity and together can be used as simple measures to predict cardiovascular risk factors in middle aged women.