A review on traditional Chinese medicine natural products and acupuncture intervention for Alzheimer's disease based on the neuroinflammatory

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset and progressive development. It is clinically characterized by cognitive impairment, memory impairment and behavioral change. Chinese herbal medicine and acupuncture are important components of traditional Chinese medicine (TCM), and are commonly used in clinical treatment of AD. This paper systematically summarizes the research progress of traditional Chinese medicine natural products and acupuncture treatment of AD, which combined with existing clinical and preclinical evidence, based on a comprehensive review of neuroinflammation, and discusses the efficacy and potential mechanisms of traditional Chinese medicine natural products and acupuncture treatment of AD. Resveratrol, curcumin, kaempferol and other Chinese herbal medicine components can significantly inhibit the neuroinflammation of AD in vivo and in vitro, and are candidates for the treatment of AD. Acupuncture can alleviate the memory and cognitive impairment of AD by improving neuroinflammation, synaptic plasticity, nerve cell apoptosis and reducing the production and aggregation of amyloid β protein (Aβ) in the brain. It has the characteristics of early, safe, effective and benign bidirectional adjustment. The purpose of this paper is to provide a basis for improving the clinical strategies of TCM for the treatment of AD.

Keywords: Acupuncture; Alzheimer’s disease; Efficacy and mechanism; Neuroinflammation; Traditional Chinese medicine natural products.

Fig. 1

An overview of pathogenesis of AD. (1) In the amyloid-producing pathway, Aβ is produced by the abnormal cleavage of APP by β-secretase 1 (BACE1) and γ-secretase. First, BACE1 cleaved the APP to produce sAPP and C-99 fragments. The C-99 fragment was cleaved by γ-secretase to produce two AICD fragments and an insoluble Aβ fragment. (2) Under normal circumstances, tau can bind to tubulin and stabilize microtubules, playing an important role in maintaining cell polarization, axonal transport and promoting neuronal growth. When tau is over-phosphorylated, tau dissociates from microtubules and aggregates into helical filaments (PHFS), which further aggregates to form NFTs, destabilizing microtubules and ultimately leading to neurofibrillary degeneration. (3) ACh is synthesized by acetyl-CoA and choline and catalyzed by choline acetyltransferase. Acetylcholinesterase in the synaptic cleft terminates signaling by hydrolyzing ACh. (4) Aβ stimulates the activation of microglia and astrocytes and induces reactive gliosis and proinflammatory signaling cascades. Activated microglia and astrocytes reduced Aβ clearance. (5) ROS promote the course of AD mainly through macromolecular peroxidation, Aβ metal ion REDOX potential and mitochondrial dysfunction, and affect cellular homeostasis, free radical production and increase the production of Aβ and p-tau

Fig. 2

Potential mechanism of traditional Chinese medicine natural products in the treatment of AD. Different types of traditional Chinese medicine monomer compounds play different roles in the process of AD. Epigallocatechin gallate (EGCG), Curcumin (CUR), Oleuropein (OLE), Resveratrol (RSV), Icariin (ICA), Ginsenoside Rg1(Rg1) and Naringenin(NAR) could inhibit the aggregation of Aβ, and resveratrol could prevent the phosphorylation of tau and reduce the level of p-tau. EGCG and RSV inhibited cholinesterase activity. kaempferol(KAF), RSV,CUR,QUE, NAR, Baicalein(BAL), Luteolin(LUT), Verbascoside(VER) inhibited neuroinflammation, Quercetin(QUE),RSV, EGCG reduce oxidative damage and other different pathways play a multi-level, multi-pathway, multi-target drug effect to prevent and control AD

Fig. 3

Potential mechanism of acupuncture in the treatment of AD. Acupuncture stimulation of different acupoints can play a role by inhibition production and aggregation of Aβ fibers, inhibit tau hyperphosphorylation, modulate the neurotransmitter release, inhibiting neuroinflammation, reducing oxidative damage and so on