Neuroprotective Effects of (-)-Epigallocatechin-3-gallate on Aging Mice Induced by D-Galactose

Abstract

Aging is a complicated multifactorial process in which a progressive decline in the physiologic function of organisms occurs. Oxidative stress and reactive oxygen species (ROS) have been proposed to be major cause of aging and other aging-related neurodegenerative conditions such as Alzheimer's disease.1,2) Aging-related oxidative damage in the brain and memory impairment mainly result from an imbalance between ROS generation and antioxidant enzyme activities. The overproduction of ROS or decrease in antioxidants in the brain can cause lipid peroxidation, nuclear and mitochondrial DNA damage, and protein oxidation and finally affect the normal functions of organisms. [3][4][5][6] D-Galactose (D-gal) is a reducing sugar normally present in the body. When present at levels greater than its normal content, it can be oxidized into aldehydes and hydrogen peroxide (H 2 O 2 ) by galactose oxidase. 7,8) It has been shown that D-galtreated animal models show aging-related changes including the impairment of spatial learning and memory, object novelty preference, and locomotor activity, 9,10) and increased production of ROS and lowered activities of antioxidant enzymes. 11,12) Other studies demonstrated that long-term subcutaneous injection of D-gal in mice induced decreased immune responses and increased cell karyopyknosis, apoptosis, and caspase-3 protein levels in hippocampal neurons.11,13) Therefore mice continuously injected with D-gal have been extensively used for pharmacologic research on brain aging.(Ϫ)-Epigallocatechin-3-gallate (EGCG) is a member of the catechin family and a major polyphenolic constituent of green tea.14) It was reported that EGCG has potent ironchelating, antioxidant, antiinflammatory, anticancer, and neuroprotective activities. [15][16][17][18][19] In particular, EGCG has been shown to have neuroprotective effects by elevating the a-secretase activity of amyloid precursor protein (APP) and conversion to soluble APP-alpha (sAPP-a) and reducing amyloid beta (Ab)-induced neurotoxicity in a 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) mouse model, the "Swedish" APP transgenic (Tg2576) mouse model of Alzheimer's disease, and N2a cells stably transfected with "Swedish" mutant human APP. 20,21) Furthermore, some studies have recently demonstrated that the neuroprotective mechanisms of EGCG are partly due to increasing activities of antioxidant enzymes and decreasing advanced glycation endproduct (AGE)-induced damage in aged rat brain or neuronal cells. 22,23) However, no study has been performed to evaluate whether EGCG has protective effects on aging mice induced by D-gal and its mechanisms of action. In the present study, we induced the aging mice model with D-gal (150 mg/kg/d, 6 weeks subcutaneously (s.c.)) and observed whether EGCG (2 mg/kg/d or 6 mg/kg/d, 4 weeks intragastrically (i.g.)) had potent antioxidant and antiapoptotic neuroprotective effects using behavioral testing and measurements of the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px), con...

Comparative Study on the Influence of Epigallocatechin-3-gallat e and/ or Coenzyme Q10 against Alzheimer's disease Induced by Aluminium in Normally-Fed and Protein Malnourished Rats

“…The present results are in accordance with the results in which EGCG increased SOD content and protected against glycation end products induced neurotoxicity by decreasing ROS and MDA [75]. Results are also in agreement with the results showed that EGCG treatment led to increase in SOD content and decrease in MDA in the hippocampus [76]. In addition, EGCG is able to bind Aβ; it may act as an antioxidant and anti-inflammatory against Aβ aggregation in hippocampus and thus have a neuroprotective effect.…”

Effect of Capparis spinosa L. on cognitive impairment induced by D-galactosein mice via inhibition of oxidative stress

“…In order to protect cells against oxidative damage induced by free radicals, endogenous antioxidant enzymes such as CAT, SOD, and GPx are activated in the body. As there is a strong correlation between oxidative stress and cognitive dysfunction, these antioxidant enzymes have important roles in fixing memory and learning deficits (7,8). In our study, decreased levels of SOD, GPx, and CAT were observed in D-galactose-treated mice.…”

“…When it is present at higher levels than normal, it can be converted to galactitol by galactose oxidase, resulting in the generation of oxygen-derived free radicals (6). Chronic systemic exposure to D-galactose induces aging-related changes such as corruption of spatial learning, memory loss, neurodegeneration, and diminishing activities of antioxidant enzymes and increased production of free radicals (7)(8)(9).…”

Isochaihulactone protects PC12 cell against H2O2 induced oxidative stress and exerts the potent anti-aging effects in D-galactose aging mouse model

“…Increasing evidence has convinced many researchers that oxidants play an important role in aging. Chronic administration of a low dose of D-galactose (D-gal) induces changes that resemble natural aging in animals [13][14][15][16][17][18][19][20] . D-galactose is a physiological nutrient obtains from lactose in milk.…”