Alzheimer’s disease (AD) is the most prevalent age-related neurodegenerative disorder worldwide, and no cure or prevention has been found for it. Extracellular senile plaque and intracellular neurofibrillary tangles are two important histopathological hallmarks of AD, which are both harmful for the cell. Senile plaques are composed of amyloid beta and neurofibrillary tangles are formed by hyperphosphorylated Tau proteins. In AD, several cellular changes also occur, including oxidative stress, neuroinflammation, accumulation of misfolded proteins, and mitochondrial dysfunction. These events promote neuronal death and finally decline memory and cognition. Lack of success of the available chemical anti-AD therapeutic agents has attracted attention to the concept of the administration of naturally occurring compounds in the treatment of AD. These compounds can be employed as a substitute for the chemical agents or complementary regimens. Several natural products are deemed capable of crossing the blood-brain barrier and are known for their central nervous system-related activity. Among the most important of them are flavonoids. Recent evidence has demonstrated their neuroprotective effects. These plant-derived compounds have strong effects on dementia-induced brain disorders because of their ability to produce antioxidants. Numerous mechanisms have been proposed for flavonoids through which they act for the prevention or recession of the disease process. According to evidence, flavonoids inhibit acetylcholinesterase (AChE), β-secretase (BACE1) and free radicals. They reduce the amyloid-beta toxicity and prevent the formation of neurofibrillary tangles. Also, they help to inhibit apoptosis induced by oxidative stress and neuroinflammation. These products have a role in synaptic plasticity and the generation of new neurons. They can affect various signaling pathways like Extracellular signal-regulated kinase (Erk), Phosphatidylinositol 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK). Overall, these processes can prevent the progression of AD and improve cognitive symptoms. In the present paper, the effect of the most important plant-derived flavonoids is briefly reviewed in different models of AD. The mechanism of action and the important signaling pathways in reducing neuroinflammation, apoptosis, and oxidative damage are discussed. It is concluded that despite the beneficial effect of these compounds, future studies are needed before flavonoids can be used as a drug in the treatment of Alzheimer’s disease.
