Polyphenols of Salix aegyptiaca modulate the activities of drug metabolizing and antioxidant enzymes, and level of lipid peroxidation.

BACKGROUND: Salix aegyptiaca is known for its medicinal properties mainly due to the presence of salicylate compounds. However, it also contains other beneficial phytochemicals such as gallic acid, quercetin, rutin and vanillin. The aim of the study was to examine the redox potential, antioxidant and anti-inflammatory activity of these phytochemicals along with acetylsalicylic acid. METHODS: The redox potential and antioxidant activity of gallic acid, quercetin, rutin, vanillin and acetylsalicylic acid were determined by oxidation-reduction potential electrode method and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, respectively. In ex vivo studies, antioxidant activity of these phytochemicals was determined by lipid peroxidation and carbonyl content assay in the liver of mice. Anti-inflammatory activity was determined by protein denaturation method. Six-week old C57BL/6 mice treated with gallic acid (100 mg/kg body weight) and acetylsalicylic acid (25 and 50 mg/kg body weight) to investigate their in vivo modulatory effects on the specific activities of drug metabolizing phase I and phase II enzymes, antioxidant enzymes and level of lipid peroxidation in liver. RESULTS: The order of ability to donate electron and antioxidant activity was found to be: gallic acid > quercetin > rutin > vanillin > acetylsalicylic acid. In ex vivo studies, the similar pattern and magnitude of inhibitory effects of these phytochemicals against peroxidative damage in microsomes and protein carbonyl in cytosolic fraction were observed. In in vivo studies, gallic acid and acetylsalicylic acid alone or in combination, enhanced the specific activities of drug metabolizing phase I and phase II enzymes as well as antioxidant enzymes and also inhibited lipid peroxidation in liver. CONCLUSIONS: These findings show a close link between the electron donation and antioxidation potential of these phytochemicals, and in turn their biological activity. Gallic acid, quercetin, rutin and vanillin were found to be better electron donors and antioxidants and therefore, might be mainly responsible for the antioxidant properties of S. aegyptiaca, while acetylsalicylic acid provided its maximum anti-inflammatory activity.

Ultrasound irradiation: a robust approach for direct functionalization of graphene oxide with thermal and antimicrobial aspects.

Sonochemical waves as mechanochemical energy was employed to exfoliate graphite oxide and functionalized graphene oxide (GrO), through a reaction of solvent and accountable for top-down and bottom-up approach respectively. The in situ formation of ester intermediate was inferred and a polymeric surface of GrO was further functionalized with 6-Aminoindazole (6-AIND) through sonochemical nucleophilic substitution reaction. As compared to conventional method the effect of ultrasound was verified for the direct functionalization of GrO. The conventional hazardous acylation step for functionalization of GrO was deleted in ultrasound assisted formation of f-(6-AIND) GrO nanocomposite, prepared by stereoselective exploitation of carboxyl groups at edges of GrO. The characterization has ascertained a covalent attachment of 6-AIND onto GrO surface with ATR-FTIR, XPS, SSNMR, TGA, DSC, XRD, AFM, RAMAN, EDX, SEM, BET and elemental analyzer. A weight loss in TGA depicts enhanced thermal stability of f-(6-AIND) GrO and a thermally sensitive behavior. The f-(6-AIND) GrO was studied for in vitro antimicrobial activity to ensure health and environmental safety. Antibacterial activity was identified against human pathogenic gram-positive (Staphylococcus aureus; ATCC 25923) and gram-negative bacteria (Escherichia coli; ATCC 25922). The antifungal activity was observed against Candida albicans (ATCC 10231).

A New Begomovirus Species in Association with Betasatellite Causing Tomato Leaf Curl Disease in Gandhinagar, India.

In December 2012, tomato leaf curl disease (ToLCD) (2) was observed in tomato-growing areas of Gandhinagar District of Gujarat, a state in northwestern India. Incidence of ToLCD was estimated to be between 40 and 70% depending on the cultivars used. Infected plants exhibited symptoms consisting of leaf rolling, leaf curling, and yellowing typical of begomoviruses. Total DNA was isolated from a single affected tomato plant (2). Begomovirus infection in this sample was established by amplification of the expected-size 550-bp DNA fragment from this extract by PCR with degenerate DNA-A primers (3). Rolling circle amplification (RCA) using ϕ29 DNA polymerase was carried out on the total DNA, followed by digestion with Bam HI. An amplicon of ~2.8 kb was gel-eluted and cloned into Bam HI linearized pBluescript II KS(+). Restriction enzyme digestion of plasmid DNA from the resulting clones indicated the presence of one type of molecule. Using PCR and universal betasatellite primers, the expected 1.3-kb fragment was amplified from the DNA extract (1). An amplicon of ~1.3 kb was gel-eluted and cloned into pTZ57RT vector. Sequence analysis revealed that DNA-A (GenBank Accession No. KC952005) is composed of 2,753 nt and showed the highest identity (87.8%) with Tomato leaf curl Kerala virus[India:Kerala:2008] (GenBank Accession No. EU910141). An analysis for recombination showed this begomovirus DNA likely to have originated by recombination between Tomato leaf curl Kerala virus and Tomato leaf curl Karnataka virus. The satellite DNA-ß (GenBank Accession No. KC952006) is composed of 1,365 nt and showed the highest identity (75.6%) with Tomato leaf curl betasatellite[India:Ludhiana:2004] (ToLCB-[IN:Lud:04]) (GenBank Accession No. AY765255). On the basis of DNA-A sequence analysis, the ICTV species demarcation criteria of 89% DNA-A sequence identity, and genome organization, the present isolate was considered as a new begomovirus species and named Tomato leaf curl Gandhinagar virus (ToLCGNV). The betasatellite shares less than 78% identity with (ToLCB-[IN:Lud:04]), it is considered a new species of betasatellite and the name, Tomato leaf curl Gandhinagar betasatellite (ToLCGNB) is proposed. Multimeric clones of the begomovirus and betasatellite DNAs were generated in a binary vector and these plasmids transformed into Agrobacterium tumefaciens. Nicotiana benthamiana and tomato plants agroinoculated with the cloned begomovirus DNA developed leaf curl symptoms, whereas plants co-agroinoculated with the cloned begomovirus and betasatellites developed more severe symptoms, including leaf rolling, leaf curling, and yellowing. The symptoms induced by the begomovirus and betasatellite DNAs were indistinguishable from those observed in the field. Thus, ToLCGNV is a new monopartite begomovirus which, in association with a new species of betasatellite, causes ToLCD in Gandhinagar, India. The presence of ToLCGNV needs to be considered, along with the already reported begomoviruses infecting tomatoes in this state, e.g., Tomato leaf curl Gujarat virus (2), in studies aimed to developing tomato cultivars with stable resistance to these tomato-infecting begomoviruses in India. References: (1) R. W. Briddon et al. Mol. Biotechnol. 20:315, 2002. (2) C. Reddy et al. Arch Virol. 150:845, 2005. (3) S. D. Wyatt and J. K. Brown. Phytopathology 86:1288, 1996.

Radiomodulation by Hoechst 33258 against radiation-induced damage in murine splenocytes.

In this study modulatory effect of Hoechst 33258 on radiation induced membrane related signaling events which ultimately leads to apoptosis has been investigated. Splenocytes from Swiss albino mice were irradiated in air at room temperature in a gamma chamber (240 TBq 60Co Model 4000 A) at the dose-rate of 0.052 Gys(-1). Membrane lipid peroxidation, fluidity, specific activities of antioxidant enzymes, levels of nitric oxide, glutathione and apoptosis in presence and absence of different concentrations of Hoechst 33258 has been assayed. DNA binding activity of nuclear factor kappa B and activator protein-1 was also assayed by electrophoretic mobility shift assay. Modulatory effect of Hoechst 33258 was examined at 3 and 5 Gy using different concentrations (10, 20 and 30 microM). Hoechst 33258 was found to inhibit radiation induced peroxidative damage and fluidity and lowered the level of nitric oxide and apoptosis--as evident by DNA ladder assay and FACS, indicating free radicals scavenging potential. Dot plot diagramme clearly showed that 30 microM Hoechst 33258 caused 14% and 19% decrease in apoptotic cells at 3 Gy and 5 Gy of radiation respectively (compared to irradiated control group). Further DNA binding activity of nuclear factor kappa B and activator protein-1 was also inhibited but the antioxidant potential of the cells was enhanced. These findings support that Hoechst 33258 protects the cell from undergoing apoptosis. Hoechst 33258 may have interacted and has an ability to protect splenocytes against radiation induced apoptosis through modulation of membrane-related signaling events and antioxidant status.

Antihyperglycemic and protective effects of Trigonella foenum graecum seed powder on biochemical alterations in alloxan diabetic rats.

BACKGROUND: Trigonella foenum-graecum, an annual herb belonging to the family Leguminosae, commonly known as fenugreek, has been reported to have hypoglycemic, hypocholesterolemic, hyperinsulinemic and antidiabetic properties. In the present study, the effect of oral feeding of Trigonella foenum-graecum seed powder (TSP) has been studied on blood glucose, monoamine oxidase (MAO), membrane fluidity, neurolipofuscin content, DNA degradation and glucose transporter-4 (GLUT4) accumulation in the alloxan-induced diabetic rat brain. METHODS: Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight) and diabetic rats were treated with 2 IU insulin, per day and 5% TSP in the diet for 21 days. RESULTS: Diabetic rats showed hyperglycemia with almost four fold high blood glucose levels. Increased MAO activity with correlated increase in genomic DNA degradation in the diabetic brain supports the hypothesis that catecholamine oxidation is an important source of oxidative stress, causing loss of membrane fluidity, increased neurolipofuscin and decreased of GLUT4 expression with diabetes in the brain. The present study showed that TSP treatment reversal the changes to near normal levels in diabetic rat brain. CONCLUSIONS: The present findings indicate that the TSP exerts its anti-diabetic and neuroprotective effects, probably mediated through a decrease in hyperglycemia and oxidative stress thereby ameliorating the control and management of diabetic complications.

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.

Antidiabetic and neuroprotective effects of Trigonella foenum-graecum seed powder in diabetic rat brain.

Trigonella foenum-graecum seed powder (TSP) has been reported to have hypoglycemic and hyperinsulinemic action. The objective of the study was to examine the antidiabetic and neuroprotective role of TSP in hyperglycemiainduced alterations in blood glucose, insulin levels and activities of membrane linked enzymes (Na+K+ATPase, Ca2+ATPase), antioxidant enzymes (superoxide dismutase, glutathione S-transferase), calcium (Ca2+) levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in the diabetic rat brain. Female Wistar rats weighing between 180 and 220 g were made diabetic by a single injection of alloxan monohydrate (15 mg/100 g body weight), diabetic rats were given 2 IU insulin, per day with 5% TSP in the diet for three weeks. A significant increase in lipid peroxidation was observed in diabetic brain. The increased lipid peroxidation following chronic hyperglycemia was accompanied with a significant increase in the neurolipofuscin deposition and Ca2+ levels with decreased activities of membrane linked ATPases and antioxidant enzymes in diabetic brain. A decrease in synaptosomal membrane fluidity may influence the activity of membrane linked enzymes in diabetes. The present study showed that TSP treatment can reverse the hyperglycemia induced changes to normal levels in diabetic rat brain. TSP administration amended effect of hyperglycemia on alterations in lipid peroxidation, restoring membrane fluidity, activities of membrane bound and antioxidant enzymes, thereby ameliorating the diabetic complications.

Chemomodulatory potential of Glycine max against murine skin and cervical papillomagenesis.

In the present study, chemopreventive potential of Glycine max (G. Max) seeds was examined against DMBA-induced skin and MCA-induced cervical papillomagenesis in Swiss albino mice. Different doses (2.5, 5, and 7.5% w/w) of G. max were provided to animals in feed. Results exhibited a significant reduction in skin as well as cervical tumor incidence and tumor multiplicity (up to 75%) at all doses of test diet as compared to the control. Relatively, 7.5% test diet was most effective in protecting the animals against carcinogenesis. Further, detoxifying enzymes and antioxidative status was also evaluated in the liver of mice to understand the role of G. max in prevention of cancer. It was observed that the test diet containing G. max significantly elevated the specific activities of glutathione-S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD), catalase (CAT), and glyoxalase I (Gly I). The test diet also elevated the content of reduced glutathione whereas it decreased the level of the peroxidative damage along with the specific activity of lactate dehydrogenase. It appeared that G. max seeds provided chemoprevention against skin and cervical papillomagenesis probably by modulating the detoxifying and antioxidative enzymes. It could be inferred that intake of G. max might help in reducing the risk of cancer.

Prepubertal daidzein exposure enhances mammary gland differentiation and regulates the expression of estrogen receptor-alpha and apoptotic proteins.

Mechanism of chemoprevention by daidzein (500 µg/g bwt) was examined by injecting it subcutaneously at 16th, 18th, and 20th day postpartum, followed by counting of terminal end buds (TEBs), terminal ducts (TDs), and lobules and immunohistochemistry of ER-α, Bcl2, Bax, and caspase-3. DNA fragmentation was also analysed to measure the apoptosis level. Estradiol benzoate (EB) (500 ng/g bwt) and dimethyl sulphoxide (DMSO) were used as reference and vehicle, respectively. Observations show a significant enhancement of mammary gland differentiation at postnatal day 21 (PND21) as well as PND50. There was a significant decrease of ER-α expression at PND21 and increase in its expression at PND50, in daidzein-treated animals. The ratio of expression of Bcl-2 to Bax proteins increased at PND50 the same whereas, it decreased at PND50 due to daidzein. An increased expression of caspase-3 and DNA fragmentation was also seen due to daidzein at PND50. The mammary gland of EB-treated animals showed response a somewhat similar to that of daidzein-treated animals.

Estradiol modulates membrane-linked ATPases, antioxidant enzymes, membrane fluidity, lipid peroxidation, and lipofuscin in aged rat liver.

Free radical production and oxidative stress are known to increase in liver during aging, and may contribute to the oxidative damage. 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 membrane linked ATPases (Na(+)K(+) ATPase, Ca(2+) ATPase), antioxidant enzymes (superoxide dismutase, glutathione-S-transferase), lipid peroxidation levels, lipofuscin content and membrane fluidity occurring in livers of female rats of 3, 12 and 24 months age groups, and to see whether these changes are restored to 3 months control levels rats after exogenous administration of 17-ß-estradiol (E2). The aged rats (12 and 24 months) were given subcutaneous injection of E2 (0.1 µg/g body weight) daily for one month. The results obtained in the present work revealed that normal aging was associated with significant decrease in the activities of membrane linked ATPases, antioxidant enzymes, membrane fluidity and an increase in lipid peroxidation and lipofuscin content in livers of aging female rats. The present study showed that E2 treatment reversed the changes to normal levels. E2 treatment may be beneficial in preventing some of the age related changes in the liver by increasing antioxidant defenses.

Protective effects of 17ß estradiol on altered age related neuronal parameters in female rat brain.

Biological aging is a fundamental process observed in almost all living beings. During aging the brain experiences structural, molecular, and functional alterations. 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 and Parkinson's disease. These changes increase during menopausal condition in females when the level of estradiol is decreased. The aim of the present study was to investigate the anti-aging and protective potential of 17ß estradiol (E2) treatment on activities of membrane linked ATPases (Na⁺K⁺ ATPase, Ca²âºATPase), antioxidant enzymes (superoxide dismutases, glutathione-S-transferases), intrasynaptosomal calcium levels, membrane fluidity and neurolipofuscin in the brain of aging 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 E2 (0.1 µg/g body weight for one month).The results obtained in the present work revealed that normal aging was associated with significant decrease in the activities of membrane linked ATPases, antioxidant enzymes and an increase in neurolipofuscin, intrasynaptosomal calcium levels in brain of aging female rats. The present study showed that E2 treatment reversed the changes to near normal levels. E2 treatment appears to be beneficial in preventing some of the age related changes in the brain, an important anti-aging effect of the hormone.

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, pharmacokinetic 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 antihyperlipedemic 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.

Physiological and biochemical effects of 17ß 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, Alzheimer's disease and Parkinson's 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 estradiol's 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.

Chemomodulatory effect of Trachyspermum ammi on murine skin and forestomach papillomagenesis.

Trachyspermum ammi seed consumed worldwide as a spice ingredient is much valued for its medicinal properties. However, it has not been investigated for its cancer chemopreventive efficacy. Herein, the chemopreventive effect of different doses (2%, 4%, and 6%) of test diets of Trachyspermum ammi seeds were examined on DMBA-induced skin and B(a)P-induced forestomach papillomagenesis, inducibility of drug metabolizing phase I and phase II enzymes, antioxidant enzymes(catalase, superoxide dismutase, glutathione peroxidase, glyoxalase I), reduced glutathione content, and peroxidative damage. Results exhibited a significant reduction in the skin as well as the forestomach tumor multiplicity with respect to all doses of test diet as compared to the control group. Biochemical assays revealed a significant increase in the activities of phase I enzymes especially with 6% test diet. A concomitant increase in the activities of the phase II enzymes and antioxidant enzymes were observed in Trachyspermum ammi treated groups. The content of reduced glutathione was significantly elevated, whereas the peroxidative damage along with lactate dehydrogenase activity exhibited a significant reduction with all the three doses of test diet. These findings were indicative of chemopreventive potential of Trachyspermum ammi seeds against carcinogenesis.

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.

Chemomodulatory action of Foeniculum vulgare (Fennel) on skin and forestomach papillomagenesis, enzymes associated with xenobiotic metabolism and antioxidant status in murine model system.

The chemopreventive effect of different doses of test diet of Foeniculum vulgare Mill (Fennel) seeds was examined on DMBA-induced skin and B(a)P-induced forestomach papillomagenesis in Swiss albino mice. To the best of our knowledge, this is the first report of Fennel seeds exhibiting a significant reduction in the skin and the forestomach tumor incidence and tumor multiplicity as compared to the control group. Further, biochemical assays showed a significant increase in the content/activities of phase I enzymes especially in the case of 6% test diet. A concomitant increase in the activities of the phase II enzymes were observed with all the doses of test diet under study. A significant enhancement in the activities of antioxidant enzymes were observed especially at 4% and 6% test diets of Fennel. Glyoxalase I activity and the content of reduced glutathione were significantly elevated. Expectedly, the levels of peroxidative damage along with lactate dehydrogenase activity, exhibited a significant reduction at all three doses of test diets. These findings were indicative of chemopreventive potential of Fennel against carcinogenesis.

Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in aging rat brain regions.

Dehydroepiandrosterone (DHEA), one of the major steroid hormones, and its ester have recently received attention with regard to aging and age-related diseases like Alzheimer and others. DHEA is synthesized de novo in the brain and its substantial fall with age has been shown to be associated with neuronal vulnerability to neurotoxicity processes. Thus, DHEA is considered to be a neuroactive pharmacological substance with potential antiaging properties. A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO). Increased MAO activity with correlated increase in lipid peroxidation in the aging rat brain supports the hypothesis that catecholamine oxidation is an important source of oxidative stress. The progressive accumulation of lipofuscin in neuronal cells is one of the most characteristic age related changes, an increase in body weight was also observed at 24 months. The objective of this study was to observe the changes in monoamine oxidase activity, lipid peroxidation levels and lipofuscin accumulation occurring in aging rat brain regions, and to see whether these changes are restored to normal levels after exogenous administration of DHEA (30 mg/kg/day 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 brain regions of 4, 14 and 24 months age group male rats. The present study showed that DHEA treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, the increased body weight at 24 months also decreased more than the age matched controls. It can therefore be suggested that DHEA's beneficial effects seemed to arise from its antioxidant, antiobesity, antilipofuscin, antilipidperoxidative and thereby anti-aging actions. The results of this study will be useful for pharmacological modification of the aging process and development of new drugs for age related disorders.