Traditional Chinese Medicine: Role in Reducing β-Amyloid, Apoptosis, Autophagy, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction of Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a progressive age-related neurodegenerative disease characterized by memory loss and cognitive impairment. The major characteristics of AD are amyloid β plaques, apoptosis, autophagy dysfunction, neuroinflammation, oxidative stress, and mitochondrial dysfunction. These are mostly used as the significant indicators for selecting the effects of potential drugs. It is imperative to explain AD pathogenesis and realize productive treatments. Although the currently used chemical drugs for clinical applications of AD are effective in managing the symptoms, they are inadequate to achieve anticipated preventive or therapeutic outcomes. There are new strategies for treating AD. Traditional Chinese Medicine (TCM) has accumulated thousands of years of experience in treating dementia. Nowadays, numerous modern pharmacological studies have verified the efficacy of many bioactive ingredients isolated from TCM for AD treatment. In this review, representative TCM for the treatment of AD are discussed, and among these herbal medicines, the Lamiaceae family accounts for the highest proportion. It is concluded that monomers and extracts from TCM have potential therapeutic effect for AD treatment.

Keywords: Alzheimer’s disease; apoptosis; autophagy; mitochondrial dysfunction; neuroinflammation; oxidative stress; traditional Chinese medicine; β-amyloid.

Figure 1

Schematic diagram depicting the pathogenesis of AD. Aβ generated from its precursor APP processing via cleavage by β-secretase and γ-secretase. Aβ deposition would cause senile plaque and further tau phosphorylation and aggregation to form NFTs, which lead to the loss of neurons and synaptic dysfunction. In addition, Aβ deposition induce mitochondrial injury and trigger ER stress, causing neuronal cell death.

Figure 2

Schematic diagram of autophagy, neuroinflammation, oxidative stress, mitochondrial dysfunction and apoptotic in AD. Autophagy is positive in alleviating AD through promoting Aβ degradation, but hyperactive autophagy is harmful to neuron survival (A). The depositions of Aβ activates the astrocytes and microglia which would secrete oxidative species, such as nitric oxide, and pro-inflammatory cytokines (B). Cytokines on the cell surface and activate pro-apoptotic signaling cascades. Mitochondrial dysfunction cause mitochondria to produce elevated levels of reactive oxygen and nitrogen species (ROS and RNS). Enhancement of ROS and RNS aggravates mitochondrial dysfunction (C, D), finally causing release of the pro-apoptotic signaling protein, CytC. CytC contributes to formation of the apoptosome (D). These factors all cause death of neuronal populations and lead to neurodegenerative disease.

Figure 3

Mechanism in treating AD based on monomer and extract of TCM.