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Research in animals and humans has indicated that polyphenols can delay the age-related decline in learning, memory and neurodegenerative diseases. Among the polyphenols, berry phenolics have extensive beneficial effects because of their antioxidant and anti-inflammatory properties. Long-term consumption of grapes results in accumulation of polyphenols in the brain, which modulates cell-signalling pathways and neutralises the redox imbalance in the aging brain. Here we review the in vivo and in vitro evidence for considering grape-derived polyphenolics, the flavonoids- catechins, epicatechin, anthocyanidin, and quercetin, and non-flavonoids-gallic acid and resveratrol, as effective dietary sources to facilitate cognition in adults and lessen the decline in the old and pathogenic states, Alzheimer's and Parkinson's disease. Furthermore, a combined intervention of polyphenols along with regular physical exercise provides cognitive benefits for the aging brain and holds promising venues for preclinical and clinical studies in formulating neuro-nutraceuticals as functional foods for a healthy brain.

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The neurotransmitter acetylcholine (ACh) is involved in memory and cognitive functions, which normally decline with age. In this chapter, we describe qRT-PCR and immunohistochemical protocols for measurement of muscarinic ACh receptor M1 (m1AChR) levels in the brains of middle-aged rats, with and without administration of grape seed proanthocyanidin extract (GSPE) and exercise training. The analyses revealed that the interventions led to an increase in m1AChR mRNA and protein levels in the CA1 subfield of hippocampus. This would be expected to enhance Ach levels at synapses and thereby boost cognitive ability. The protocols can be applied to m1AChR measurements in neurodegenerative diseases and dementia.

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A series of spiro-[indoline-3,3'-pyrrolizin/pyrrolidin]-2-ones, 4, 5 and 6 were synthesized in a sequential manner from Cu-TEMPO catalyzed dehydrogenation of alkylated ketones, 1 followed by 1,3-dipolar cycloaddition of azomethine ylides via decarboxylative condensation of isatin, 2 and l-proline/sarcosine, 3 in high regioselectivities and yields. The detailed mechanistic studies were performed to identify the reaction intermediates, which revealed that the reaction proceeds via dehydrogenative cycloaddition. Additionally, the regio and stereochemistry of the synthesized derivatives were affirmed by 2D NMR spectroscopic studies. The synthesized derivatives were explored further with molecular docking, in vitro antioxidant, and anti-diabetic activities.

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This study was aimed at determining the effect of vitamin E, vitamin C, and carnitine on intermittent hypobaric-hypoxia-induced oxidative stress (OS) in erythrocytes. For this purpose, male Wistar rats of 4 months of age were orally supplemented with one of the antioxidants prior to exposure to altitudes of 5700 m or 6300 m. Hemoglobin (Hb) and OS indices such as osmotic fragility and hemolysis were measured together with lipid peroxidation (LPO) and protein oxidation. The increase in Hb was accompanied by increase in activities of antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT) during exposure to both the altitudes without any further elevation by supplements. The extent of reduction in osmotic fragility and hemolysis by vitamin E and carnitine was greater at 6300 m than at 5700 m. Increase in LPO products, for example, malondialdehyde (MDA) and lipofuscin-like autofluorescent substances (AFS) was noticeable at both the altitudes, and vitamin E and carnitine were effective in reducing LPO. While protein oxidation products such as carbonyl content (PrC) and advanced oxidation protein products (AOPP) increased at 6300 m, protein sulphydryl (P-SH) content decreased. P-SH levels were restored on supplementation of antioxidants. Hence, our results indicate that vitamin E, vitamin C, and carnitine may be beneficial in overcoming OS and hemolysis under situations such as intermittent hypobaric hypoxia (IHH) and hypobarotherapy wherein hypoxia is used to correct many pathological situations in humans. Further, this study suggests that supplementation of vitamin E, vitamin C, and L-carnitine alone and not in combination can be beneficial in attenuating the OS associated with IHH compared to the unsupplemented rats exposed to two different altitudes.

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We have evaluated the effect of exercise, Vitamin E and a combination of both on the antioxidant enzymes (AOEs)-superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) along with the products of lipid peroxidation (LP)-malondialdehyde (MDA) and lipofuscin-like auto fluorescent substances (LF-like AFS) in discrete brain regions of rats of 4 (young adults), 8 (old adults), 12 (middle-age) and 22 months (mos) old of age. Hippocampus (HC) showed greater increase in GSH-Px activity than cerebral cortex (CC) to exercise and Vitamin E and was irrespective of the age. A combination of both was effective in the CC of all age groups but not in the supplemented sedentary of 12- and 22-mo-olds. CAT activity increased significantly in the HC of supplemented and trained rats but not in the combination group of any age. SOD increased in both the regions of supplemented trainees. However, old were more benefited in terms of maximal elevation in the HC. Vitamin E reduced MDA content in both regions of adult. LF-like AFS decreased significantly in supplemented sedentary and trainees of all ages. Our results demonstrate that an age-related deficit in AOEs in the CC and HC can be overcome through Vitamin E plus exercise, and further suggests the rationale for looking at these markers of oxidative stress in several age-related neuronal diseases.

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The interventricular site has been proposed as one of the sites for the myocyte cell death with aging and thereby enhancing the possibility of ventricular dysfunction with aging. Variations in lactate dehydrogenase (LDH), a key glycolytic regulatory enzyme along with its isomers were used as indices to evaluate the anaerobic capacity of the interventricular septum (IVS) in 2-month-old (young) and 12-month-old (middle-aged) rats trained to swim at 25 degrees C (cold, C) and 35 degrees C (thermo neutral, N) temperatures. Blood lactate (La) and LDH along with its isoenzymes in the IVS were assessed and compared with untrained and sedentary rats. Increased septal and heart weight was indicative of age-related hypertrophy accompanied by increased septal thickness. Elevated total LDH activity was evident in both the trained groups in the young. The middle-aged animals exhibited lesser variations in LDH and, H and M subunits. The data suggest an efficient adaptability of the IVS of young rats to physical training in contrast to a poor response by the IVS of middle-aged animals.

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