FIGURE 4 Therapeutic mechanism of Chinese herbal medicine on Alzheimer’s disease through cholinergic pathway
In the cholinergic pathway related to Alzheimer’s disease (AD), choline and acetyl-coenzyme A (AcCoA) are catalyzed by acetylcholine transferase (ChAT) to produce ACh, which is transported to the synaptic cleft. The activity and content of acetylcholinesterase (AChE) directly affect the effect of ACh. The activation of α7nAChR and mAChR increases the expression of amyloid precursor protein (APP) and reduces non-β amyloid peptides (Aβ) by increasing Aβ metabolism. In the early stage of AD, a low concentration of Aβ activates hippocampal astrocytes to protect nerves, but in the middle and late stages, it accumulates too much to form a vicious circle, and a large amount of Aβ is deposited in a feedback manner. Aβ and α7nAChR have high affinity and combine to form a complex, thereby blocking neurotransmitter transmission and signal transmission, causing nerve cell death. Both α7nAChR activation and M1mAChR activation down-regulate Glycogen synthase kinase-3β (GSK-3β) and reduce the hyperphosphorylation of tau protein, thereby reducing neurofibrillary tangles. Studies have found that Chinese herbal medicine increases the ACh level by increasing ChAT expression and inhibiting AChE. In addition, it activates α7nAChR, M1mAChR, and M3mAChR, inhibits neuroinflammation, reduces Aβ deposition, reduces nerve cell death, and reduces tau protein hyperphosphorylation, thereby achieving AD treatment.