Asia Taha

A metabolic and functional overview of brain aging linked to neurological disorders

Close correlations have recently been shown among the late onset complications encountered in diabetes and aging linked to neurobiological disorders. Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimer’s disease and Parkinson’s disease, dementia, cognitive dysfunction and hypernatremia. Beside the sex hormones other hormonal changes are also known to occur during aging and many common problems encountered in the aging process can be related to neuroendocrine phenomena. Diabetes mellitus is associated with moderate cognitive deficits and neurophysiologic and structural changes in the brain, a condition that may be referred to as diabetes encephalopathy; diabetes increases the risk of dementia especially in the elderly. The current view is that the diabetic brain features many symptoms that are best described as accelerated brain aging. This review presents and compares biochemical, physiological, electrophysiological, molecular, and pathological data from neuronal tissue of aging and hormone treated control and diabetic animals to arrive at the similarities among the two naturally occuring physiological conditions. Animal models can make a substantial contribution to understanding of the pathogenesis, which share many features with mechanism underlying brain aging. By studying the pathogenesis, targets for pharmacology can be identified, finally leading to delay or prevention of these complications. Antiaging strategies using hormone therapy, chemical and herbal compounds were carried out for reversal of aging effects. Neuronal markers have been presented in this review and similarities in changes were seen among the aging, diabetes and hormone treated (estrogen, DHEA and insulin) brains from these animals. A close correlation was observed in parameters like oxidative stress, enzyme changes, and pathological changes like lipofuscin accumulation in aging and diabetic brain.

Metabolic and molecular action of Trigonella foenum-graecum (fenugreek) and trace metals in experimental diabetic tissues

Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycaemia resulting in defective insulin secretion, resistance to insulin action or both. The use of biguanides, sulphonylurea and other drugs are valuable in the treatment of diabetes mellitus; their use, however, is restricted by their limited action, pharmaco-kinetic properties, secondary failure rates and side effects. Trigonella foenum-graecum, commonly known as fenugreek, is a plant that has been extensively used as a source of antidiabetic compounds from its seeds and leaf extracts. Preliminary human trials and animal experiments suggest possible hypoglycaemic and anti-hyperlipedemic properties of fenugreek seed powder taken orally. Our results show that the action of fenugreek in lowering blood glucose levels is almost comparable to the effect of insulin. Combination with trace metal showed that vanadium had additive effects and manganese had additive effects with insulin on in vitro system in control and diabetic animals of young and old ages using adipose tissue. The Trigonella and vanadium effects were studied in a number of tissues including liver, kidney, brain peripheral nerve, heart, red blood cells and skeletal muscle. Addition of Trigonella to vanadium significantly removed the toxicity of vanadium when used to reduce blood glucose levels. Administration of the various combinations of the antidiabetic compounds to diabetic animals was found to reverse most of the diabetic effects studied at physiological, biochemical, histochemical and molecular levels. Results of the key enzymes of metabolic pathways have been summarized together with glucose transporter, Glut-4 and insulin levels. Our findings illustrate and elucidate the antidiabetic/insulin mimetic effects of Trigonella, manganese and vanadium.

Amelioration of altered antioxidant status and membrane linked functions by vanadium and Trigonella in alloxan diabetic rat brains.

Trigonella foenum graecum seed powder (TSP) and sodium orthovanadate (SOV) have been reported to have antidiabetic effects. However, SOV exerts hypoglycemic effects at relatively high doses with several toxic effects. We used low doses of vanadate in combination with TSP and evaluated their antidiabetic effects on antioxidant enzymes and membrane-linked functions in diabetic rat brains. In rats, diabetes was induced by alloxan monohydrate (15 mg/100 g body wt.) and they were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP and a combination of 0.2 mg/ml SOV with 5% TSP for 21 days. Blood glucose levels, activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), Na+/K+ ATPase, membrane lipid peroxidation and fluidity were determined in different fractions of whole brain after 21 days of treatment. Diabetic rats showed high blood glucose (P < 0.001), decreased activities of SOD, catalase and Na+/K+ ATPase (P < 0.01,P < 0.001 andP < 0.01), increased levels of GPx and MDA (P < 0.01 andP < 0.001) and decreased membrane fluidity (P < 0.01). Treatment with different antidiabetic compounds restored the above-altered parameters. Combined dose ofTrigonella and vanadate was found to be the most effective treatment in normalizing these alterations. Lower doses of vanadate could be used in combination with TSP to effectively counter diabetic alterations without any toxic effects.

Long-term effect of Trigonella foenum graecum and its combination with sodium orthovanadate in preventing histopathological and biochemical abnormalities in diabetic rat ocular tissues

Trigonella foenum graecum seed powder (TSP) and Sodium Orthovanadate (SOV) have been shown to demonstrate antidiabetic effects by stabilizing glucose homeostasis and carbohydrate metabolism in experimental type-1 diabetes. However their efficacy in controlling histopathological and biochemical abnormalities in ocular tissues associated with diabetic retinopathy is not known. The purpose of this study was to investigate the comparative efficacy of individual as well as combination therapy of TSP and SOV in 8 weeks diabetic rat lens and retina. Retinas and lenses were taken from control, alloxan-induced diabetic rats and diabetic rats treated separately with insulin, 5%TSP, SOV (0.6 mg/ml) and a combined dose of SOV (0.2 mg/ml) and 5%TSP for 60 days. Control and each experimental group had six rats. Alterations in the activities of enzymes HK (hexokinase), AR (aldose reductase), SDH (sorbitol dehydrogenase), G-6-PD (glucose-6-phosphate dehydrogenase), GPx (glutathione peroxidase), GR (glutathione reductase) and levels of metabolites like sorbitol, fructose, glucose, MDA (malondialdehyde) and GSH (reduced glutathione) were measured in the cytosolic fraction of lenses besides measuring blood glucose levels and glycosylated haemoglobin. Histopathological abnormalities were studied in the lens using photomicrography and retina using transmission electron microscopy. Blood glucose, glycosylated haemoglobin levels and polyol pathway enzymes AR and SDH increased significantly causing accumulation of sorbitol and fructose in the diabetic lens and treatment with SOV and TSP significantly (p < 0.05) decreased these to control levels. Similarly, SOV and TSP treatments modulated the activities of HK, G-6-PD, GPx and GR in the rat lens to control values. Ultrastructure of the diabetic retina revealed disintegration of the inner nuclear layer cells with reduction in rough endoplasmic reticulum and swelling of mitochondria in the bipolar cells; and these histopathological events were effectively restored to control state by SOV and TSP treatments. In this study SOV and TSP effectively controlled ocular histopathological and biochemical abnormalities associated with experimental type-1 diabetes, and a combination regimen of low dose of SOV with TSP demonstrated the most significant effect. In conclusion, the potential of SOV and TSP alone or in low dose combination may be considered as promising approaches for the prevention of diabetic retinopathy and other ocular disorders.

Low doses of vanadate and Trigonella synergistically regulate Na+/K+-ATPase activity and GLUT4 translocation in alloxan-diabetic rats

Oral administration of vanadate to diabetic animals have been shown to stabilize the glucose homeostasis and restore altered metabolic pathways. However, vanadate exerts these effects at relatively high doses with several toxic effects. Low doses of vanadate are relatively safe but unable to elicit any antidiabetic effects. The present study explored the prospect of using low doses of vanadate with Trigonella foenum graecum, seed powder (TSP), another antidiabetic agent, and to evaluate their antidiabetic effect in diabetic rats. Alloxan diabetic rats were treated with insulin, vanadate, TSP and low doses of vanadate with TSP for three weeks. The effect of these antidiabetic compounds was examined on general physiological parameters, Na+/K+ ATPase activity, membrane lipid peroxidation and membrane fluidity in liver, kidney and heart tissues. Expression of glucose transporter (GLUT4) protein was also examined by immunoblotting method in experimental rat heart after three weeks of diabetes induction. Diabetic rats showed high blood glucose levels. Activity of Na+/K+ ATPase decreased in diabetic liver and heart. However, kidney showed a significant increase in Na+/K+ ATPase activity. Diabetic rats exhibited an increased level of lipid peroxidation and decreased membrane fluidity. GLUT4 distribution was also significantly lowered in heart of alloxan diabetic rats. Treatment of diabetic rats with insulin, TSP, vanadate and a combined therapy of lower dose of vanadate with TSP revived normoglycemia and restored the altered level of Na+/K+ ATPase, lipid peroxidation and membrane fluidity and also induced the redistribution of GLUT4 transporter. TSP treatment alone is partially effective in restoring the above diabetes-induced alterations. Combined therapy of vanadate and TSP was the most effective in normalization of altered membrane linked functions and GLUT4 distribution without any harmful side effect.

Physiological and biochemical effects of 17β estradiol in aging female rat brain.

Aging in females and males is considered as the end of natural protection against age related diseases like osteoporosis, coronary heart disease, diabetes, Alzheimers disease and Parkinsons disease. These changes increase during menopausal condition in females when the level of estradiol is decreased. The objective of this study was to observe the changes in activities of monoamine oxidase, glucose transporter-4 levels, membrane fluidity, lipid peroxidation levels and lipofuscin accumulation occurring in brains of female rats of 3 months (young), 12 months (adult) and 24 months (old) age groups, and to see whether these changes are restored to normal levels after exogenous administration of estradiol (0.1 μg/g body weight for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in the brains of aging female rats, and a decrease in glucose transporter-4 level and membrane fluidity. Our data showed that estradiol treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, and a reversal of glucose transporter-4 levels and membrane fluidity was achieved, therefore it can be concluded from the present findings that estradiols beneficial effects seemed to arise from its antilipofuscin, antioxidant and antilipidperoxidative effects, implying an overall anti-aging action. The results of this study will be useful for pharmacological modification of the aging process and applying new strategies for control of age related disorders.

Beneficial effects of Trigonella foenum graecum and sodium orthovanadate on metabolic parameters in experimental diabetes.

Oxidative stress in diabetic tissues is accompanied by high‐level of free radicals with simultaneously declined antioxidant enzymes status leading to cell membrane damage. The present study was carried out to observe the effect of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP) administration on blood glucose and insulin levels, antioxidant enzymes, lipid peroxidation, pyruvate kinase, lactate dehydrogenase and protein kinase C in heart, muscle and brain of the alloxan‐induced diabetic rats to see whether the treatment with SOV and TSP was capable of reversing the diabetic effects. Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight), and rats were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV and 5% TSP separately for 21 days. Blood glucose levels increased markedly in diabetic rats, animals treated with a combined dose of SOV and TSP had glucose levels almost comparable with controls, similar results were obtained in the activities of pyruvate kinase, lactate dehydrogenase, antioxidant enzymes and protein kinase C in diabetic animals. Our results showed that lower doses of SOV (0.2 mg/ml) could be used in combination with TSP to effectively reverse diabetic alterations in experimental diabetes. Copyright

Sodium Orthovanadate and Trigonella Foenum Graecum Prevents Neuronal Parameters Decline and Impaired Glucose Homeostasis in Alloxan Diabetic Rats

Hyperglycemia is the most important contributor in the onset and progress of diabetic complications mainly by producing oxidative stress. The present study was carried out to observe, the antihyperglycemic effect of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP) administration on blood glucose and insulin levels, membrane linked enzymes (monoamine oxidase, acetylcholinesterase, Ca2+ATPase), intracellular calcium (Ca2+) levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in brain of the alloxan induced diabetic rats and to see whether the treatment with SOV and TSP was capable of reversing the diabetic effects. Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight) and rats were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV and 5% TSP separately for three weeks. Diabetic rats showed hyperglycemia with almost four fold high blood glucose levels. Activities of acetylcholinesterase and Ca2+ATPase decreased in diabetic rat brain. Diabetic rats exhibited an increased level of intracellular Ca2+ levels, lipid peroxidation, neurolipofuscin accumulations and monoamine oxidase activity. Treatment of diabetic rats with insulin, TSP, SOV and a combined therapy of lower dose of SOV with TSP revived normoglycemia and restored the altered level of membrane bound enzymes, lipid peroxidation and neurolipofuscin accumulation. Our results showed that lower doses of SOV (0.2 mg/ml) could be used in combination with TSP in normalization of altered metabolic parameters and membrane linked enzymes without any harmful side effect.