Content area
Full Text
Introduction
Alzheimer's disease (AD), due to neuron loss and synaptic degeneration, is characterized by a significant decline in cognitive function and poor prognosis, which accounts for 60-70% of all types of dementia (1,2). Although the aggregated amyloid β (Aβ) titanium and hyper-phosphorylated (p-) Tau may exhibit neurotoxicity in the development of AD, the exact therapeutic targets have not been successfully identified due to the complex mechanism associated with the pathogenesis of this disease (3). Among the various hypotheses, the occurrence of oxidative stress and neuronal apoptosis in AD has been accepted. Oxidative stress, represented by the over-accumulation of reactive oxygen species (ROS), is responsible for the damage to the mitochondria, membrane lipids, and nucleic acids (4). Oxidative stress promotes Aβ aggregation, which exhibits a direct toxic effect to its surrounding neurons, leading to the susceptibility of neurons to free radicals, particularly ROS (5,6).
As a major cellular source of ROS, mitochondria serve an important role in the pathophysiology of neurode-generative diseases (7). The disruption of mitochondrial homeostasis caused by the high levels of ROS further leads to the over-production of ROS and other cytokines, such as cytochrome c, which induces the cell apoptosis program (8,9). The extremely high levels of glutamate (Glu) associated with ROS accumulation, a central nervous neurotransmitter, damages neurons (10); however, during the onset of oxidative stress, the transcription factor NF-E2p45-related factor 2 (Nrf2) helps maintain cellular redox homeostasis, and supports the structure and functional integrity of the mitochondria (11). Furthermore, the deletion of Nrf2 can increase the intracellular levels of Aβ in mice with AD (12).
The occurrence of AD is rapidly increasing worldwide, and according to statistics, there are >40 million patients globally (13). As the prevention and treatment of AD has been a serious challenge, potential agents applied in clinics have failed to effectively treat patients with AD. In addition, the adverse effects of these agents have been noted, including gastrointestinal discomfort, difficulty sleeping and muscle spasms (14). Herbal compounds have been reported as a large and underappreciated source of potential agents to treat or prevent AD (15,16). Evodiamine treatment resulted in the return of AD-associated symptoms via modulating oxidative stress-mediated apoptosis in L-glutamate (L-Glu)-damaged HT22 cells, and a mouse model with AlCl3- and D-galactose (D-gal)-induced...