Neuroprotective potential of epigallo catechin-3-gallate in PC-12 cells.

Oxidative stress is a major player in aging and neurodegenerative disorders. Macromolecular damage occurs as a result of oxidative stress that affects the mitochondria. Mitochondrial damage leads to cell death by apoptosis or necrosis. EGCG is a tea polyphenol that protects the cells against oxidative stress. Neuroprotective potential of EGCG was tested against H(2)O(2) induced oxidative stress in PC-12 cells. PC-12 cells were grown in tissue culture flasks. Oxidative stress was induced by adding H(2)O(2) to the cells. EGCG was also added and the cell death was assessed using MTT assay. Oxidative stress was assessed by protein carbonyl and thiol status. Mitochondrial membrane potential was studied using JC-1 staining. TNF-α levels were assessed using ELISA. H(2)O(2) increased the protein carbonyl content and reduced the thiol status in the PC-12 cells. Cell death was increased in H(2)O(2) treated cells as shown by MTT assay. Mitochondrial membrane potential was also decreased along with increase in TNF-α level in H(2)O(2) treated cells. EGCG brought about an increase in the cellular thiol status and decreased the protein carbonyl content in the PC-12 cells. Cell death was attenuated by EGCG treatment along with an increase in mitochondrial membrane potential and decrease in TNF-α level. EGCG conferred its antioxidant potential to PC-12 cells as evident by decreased protein damage. Mitochondrial membrane potential was improved along with a decrement in the cell death in PC-12 cells. EGCG acts as a good neutraceutical antioxidant to render neuroprotectivity to PC-12 cells.

Impact of epigallo catechin-3-gallate on acetylcholine-acetylcholine esterase cycle in aged rat brain.

Neurotransmission plays an important role in communication of messages in brain. Cholinergic alterations during aging are associated with learning and memory. Neurotransmitters and enzymes that influence these neurotransmitters are significant in age-associated memory. Neurotransmitters like acetylcholine, serotonin and dopamine levels were studied. Kinetics of acetylcholine esterase was studied. There was an alteration in km and Vm values which was brought back to near-normalcy by EGCG. Behavioural changes were assessed by radial maze experiment. EGCG, a good neuroprotective drug proved to alleviate the behavioural alterations in aged rat brain. Acetylcholine esterase was partially purified from rat brain and assayed in vitro. Several modifiers like EGCG and donepezil were added in silico and the activity of the enzyme was calculated. EGCG increased the activity when compared to negative control, donepezil. Using bioinformatics tools EGCG, acetylcholine and donepezil were docked with acetylcholine esterase. EGCG formed a good docking-complex with the enzyme. Thus, it shall be hypothesized that the neuroprotective activity of EGCG might be due to its influence on cholinergic neurotransmission thereby improving the cognitive functions of the brain.

Mitochondrial alterations in aging rat brain: effective role of (-)-epigallo catechin gallate.

Aging is a multi-factorial process which involves deprivation in body's metabolism. Brain mitochondria are prone to oxidative damage owing to their high metabolic rate. The decline in antioxidant system during aging augments the neuronal damage to mitochondrial components like antioxidant system, Kreb's cycle enzymes and electron transport chain complexes. Since brain is an organ rich in fatty acids, lipid peroxidation products like hydroxynonenal are predominant. Those lipid peroxidation products conjugate with amino acids to form adducts which alter their structural and functional properties. Epigallo catechin gallate is a potent antioxidant which is rich in green tea extract. This study elucidated the antioxidant potential of epigallo catechin gallate to counteract the mitochondrial oxidative damage in brain. The study comprised of young (3-4 months old; 150+/-20 g) and aged (above 24 months; 420+/-20 g) male albino rats of Wistar strain in Groups I and II. Groups III and IV comprised of young and aged rats supplemented with epigallo catechin gallate (2mg/kg body weight) for 30 days. Antioxidants, Kreb's cycle enzymes and electron transport chain complexes were assayed in the mitochondrial fraction. Hydroxynonenal expression was carried out using immunohistochemical analysis. Epigallo catechin gallate supplementation decreased the expression of hydroxynonenal in aged brain, up-regulated the antioxidant system and augmented the activities of Kreb's cycle enzymes and electron transport chain complexes in aged brain mitochondria thus proving its antioxidant potential at the level of mitochondria.

Attenuation of senescence-induced oxidative exacerbations in aged rat brain by (-)-epigallocatechin-3-gallate.

Aging is a complex biological phenomenon which involves free radicals and oxidative stress. Brain is more susceptible and vulnerable to oxidative damage due to its high-polyunsaturated fatty acid content and high rate of aerobic metabolism. Since the antioxidant defense system is diminished during aging, antioxidant supplementation might be a protective strategy against age-associated oxidative damage. The present study evaluates the antioxidant potential of (-)-epigallocatechin-3-gallate (EGCG), a major polyphenol present in green tea against age-associated oxidative damage in rat brain. Male albino rats of Wistar strain were used in the study. Group I (young) and Group II (aged) rats received saline alone orally for 30 days. Group III (young) and Group IV (aged) rats received EGCG (2mg/kg body weight/day) orally for 30 days. Antioxidant status and oxidative damage were assessed. EGCG brought about an augmentation in the activities of enzymic antioxidants like superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and improved the non-enzymic antioxidants like tocopherol, ascorbic acid and glutathione. EGCG ameliorated the malondialdehyde and protein carbonyl levels. Thus, EGCG has emerged out as a good antioxidant neutraceutical and a neuroprotective agent in alleviating the age-associated oxidative damage in aged rat brain.

Repletion of antioxidant status by EGCG and retardation of oxidative damage induced macromolecular anomalies in aged rats.

Ageing is defined as the loss of ability to maintain cellular homeostasis of an organism associated with the free radical-elicited oxidative damage to cellular macromolecules. The aim of this study was to evaluate the efficacy of epigallocatechin-3-gallate (EGCG), the key component of green tea catechins on attenuating the age associated oxidative perturbances by assessing the redox status in mitotic (liver) and post-mitotic (skeletal muscle) tissues of young and aged rats. From the results, we observed an increase in the marker for oxidative damage such as lipid peroxidation and protein carbonyl content in aged rats, when compared to young rats. This was accompanied with decreased levels of both enzymic and non-enzymic antioxidants and redox index. On supplementation with EGCG (100 mg/kg body weight by oral gavage for 30 days), the levels of lipid peroxidation and protein carbonyl content were significantly decreased in aged rats, possibly by enhancing the GSH redox status, and both enzymic and non-enzymic antioxidants status. In conclusion, this study supports the beneficial effect of EGCG in alleviating oxidative disturbances in ageing and retard the age associated derangements in both mitotic and post-mitotic tissues.