A Review on Potential Mechanisms of Terminalia chebula in Alzheimer’s Disease
Table 2
Major effects of oxidative stress in the pathogenesis of Alzheimer’s disease.
Effects of ROS
Result
Biological evidence(s)
Protein oxidation
Increased protein carbonyl content
Increased protein oxidation in frontal pole and occipital pole [113] Decreased ratio of (MAL-6)/(W/S) in AD hippocampus and inferior parietal lobule, decreased the W/S ratio in in vitro models of human synaptosomes oxidation by ROS [114]
DNA oxidation
Direct damage to DNA structure
3-fold increase in mitochondrial DNA oxidation in parietal cortex in AD [115] Increase in oxidative damage to nuclear DNA in AD compared with age-matched control subjects [116] 8-hydroxy-2-deoxyguanosine as a marker of DNA oxidation increases in AD [117]
Lipid peroxidation
Brain phospholipid damage
Increased TBARS levels in AD in hippocampus, piriform cortex, and amygdala [118] Increased lipid peroxidation of AD brain homogenates in vitro due to Fe-H2O2 [119] Increased apoptosis in cultured DS and AD neurons inhibited by antioxidant enzymes [112, 120] Decrease in PC, PE, phospholipid precursors, choline, and ethanolamine in hippocampus and inferior parietal lobule in AD [121] Increased aldehydes as a cytotoxic agent in the brain of AD patients [122]
Antioxidant enzymes
Changes in enzymes contents
Elevated GSH-Px, GSSG-R, and CAT activity in hippocampus and amygdala in AD [118] Many studies showed no elevation in enzyme activity [123, 124] or decrease in activity [125]
AGE formation
Pathological changes in protein structure and action
Accelerates aggregation of soluble nonfibrillar A and tau [126]
MAL-6: weakly immobilized protein bound spin label; W/S: strongly immobilized protein bound spin label; TBARS: thiobarbituric acid reactive substances; DS: Down syndrome; PC: phosphatidylcholine; PE: phosphatidylethanolamine; GSH-Px: glutathione peroxidase; GSSG-R: glutathione reductase; CAT: catalase; AGE: advanced glycation end products.