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.