Table 3 Potential mechanisms of acupuncture ingredients for AD

1

MA

GV20, GV26, DU29

Two rotations per second for 30 s at each point

senescence-accelerated mouse prone 8 (SAMP8)

-

Iimproved spatial learning and memory ability, the level of glucose metabolism in the brain, and the content of Aβ amyloid in the cortex

[231]

2

EA

GV29, IL20

1.5 mA, 15 Hz

Aβ1-42-induced AD rat model

PI3K/AKT/GSK-3β

Rescue the cognitive deficits of Aβ1-42-induced AD rats by improving synaptic plasticity, neuro-apoptosis and neuro-inflammation through enhancing PI3K/AKT/GSK-3β signaling pathway

[189]

3

MA

CV17, CV12, CV6, ST36, SP10

Moderate reinforcing-reducing manipulation for 210 s

SAMP8

bFGF, EGF, BDNF

Regulate the cytokine levels associated with survival, pro liferation, and differentiation of NSCs in hippocampal mi croenvironment, to promote the repair of damaged cells, resulting in improved cognitive performance in mice

[232]

4

MA

GV24, GB13

The twisting was performed at a range of 90–180° and a rate of 100–150 times/min

Aβ1-40-induced AD rat model

-

Altering cerebral glucose metabolism (CGM), regulating the distribution of neurotransmitters and enhancing synaptic plasticity

[167]

5

MA

HT7

Twisted/rotated at a frequency of 120–150 times per min for 3 min

IBO-induced AD rat model

-

Improve CGM

[233]

6

MA

CV17, CV12, CV6, ST36, SP10

The needles inserted at each location were stimulated for 30 s and the total treatment time was 210 s

SAMP8

SOD, GSH-Px; superoxide anion, protein carbonyl; Hsp84 and Hsp86 mRNA and protein

Delay brain ageing in SAMP8 mice by reducing oxidative protein damage and promoting Hsp84 and Hsp86 expression

[180]

7

MA

DU20, LI4, BL13, BL20, BL23, ST36, SP6

Acupuncture treatment for 20 min per day

APP/PS1 double-transgenic mice

IL-10, LPS

Regulated the Aβ and tau protein concentration as well as the levels of IL-10 and LPS

[234]

8

EA

LI20,EX-HN3

Current

intensity: 1–3 mA, voltage: 1–3 V,80–100 Hz

AD rat model

SOD, GSH-Px

Increase learning-memory ability, decrease MDA content, and increase SOD and GSH-Px activities in the hippocampus

[68]

9

MA

RN17,RN12,RN4,SP10,ST36

Slowly rotated for 30 s every 5 min and lasted for 15 min

SAMP8

PI3K/PDK1/nPKC/Rac 1

Downregulating PI3K/PDK1/nPKC/Rac 1 signaling pathway

[160]

10

MA

CV17, CV12, CV6, ST36, SP10

Each acupuncture point was needled for 30 s, and each non-acupuncture point was needled for 105 s, in order that the total duration of stimulation was 210 s in each group

SAMP8

-

Upregulation of G protein activity and stabilisation of the cellular signal

[235]

11

EA

GV24, GB13

0.3 mA, 2 Hz, 15 min

Aβ-induced AD rat model (5xFAD)

AKT-MAPK1-MTORC1

Inhibited glial cell activation in the prefrontal cortex and hippocampus of 5xFAD, activated TFEB via inhibiting the AKT-MAPK1-MTORC1 pathway, thus promoting ALP in the brains

[143]

12

MA

DU24, GB13

Twisting frequency of 80 ± 5/min, a twisting amplitude of 180° ± 5°, and a sustainable stimulation for 2 min, with 1 min rest; this was repeated for 15 min in total

Aβ1-40-induced AD rat model

neurotransmitter acetylcholine

Related to the role of Zhisanzhen in increasing chAT and Ache activity, decreasing oxidative stress and inhibiting neuronal apoptosis

[236]

13

EA

GV24, GB13

30 Hz, 1.0 mA, 30 min

Aβ1-40-induced AD rat model

-

Decreasing the levels of Aβ, p-tau (s396) and p-tau (s404) in the brain

[165]

14

EA

KI3

15 min, 1 mA, 2 Hz

5xFAD mice model

-

ameliorates cognitive impairment via inhibition of synaptic degeneration and neuroinflammation

[130]

15

MA

ST36

Twirling reinforcing manipulation

CMi rats

NF-κB-p53

Inhibited activation of NF-κB and its downstream target gene p53

[237]

16

MA

CV17, CV12, CV6, ST36, SP10

Rate of twice a second for 30 s at each point

SAMP8

-

Reduced neuron loss in hippocampal regions CA3 and DG

[238]

17

MA

CV17, CV12, CV6, ST36, SP10

Twirling reinforcing manipulation

SAMP8

-

Improve the cognitive impairment by increasing TPI activity, thus correcting the abnormal glycolysis metabolism and maintaining the brain homeostasis and internal environment

[239]

18

EA

GV20, BL23

20 min, 2 Hz,2 mA

Aβ1-40-induced AD rat model

PPAR-γ;

p-p38MAPK

activation of PPAR-γ and inhibition of p-p38MAPK expression

[240]

19

MA

ST36

The twisting was performed within the range of 90–180° at a rate of 60–90 times/min

AD rat model

-

Increase blood perfusion and glycol metabolism in certain brain areas

[241]

20

EA

GV20,GV26,GV29

20 min, 2 Hz,1 mA

APP/PS1 mice

-

Enhancing glucose metabolism and inhibiting inflammation-mediated Aβ deposition

[242]

21

EA

GV20, KI1

30 min, 2/15 Hz,1 mA

Aβ1-42-induced AD rat model

NOX2

Alleviation of neuronal injury and inhibition of NOX2-related oxidative stress

[181]

22

EA

GV20,GV26,GV29

2 Hz,1 mA

SAMP8

AQP4

Reduce Aβ accumulation

[169]

23

EA

GV20,GV29

2 Hz,0.1 mA

SAMP8

TREM2

Upregulate TREM2 expression in the hippocampus

[243]

24

EA

GV20, BL23

20 Hz,2 mA

Aβ1-40-induced AD rat model

LC3II/LC3I ratios, Beclin-1

Reduces neuronal apoptosis, enhances degradation of Aβ, and improves learning/memory

[244]

25

EA

DU24, DU20

30 min, 1/20 Hz,1 mA

APP/PS1 mice

Regulate microglial polarization and decrease Aβ plaque

[245]

26

EA

DU24, DU20

30 min, 2/20 Hz,1 mA

5xFAD mice

MS/VDB-DG cholinergic neural circuit

Improve the early pattern separation impairment by activating the MS/VDB-DG cholinergic neural circuit

[246]

27

EA

DU20, BL23

15 min, 2 Hz,2 mA

APP/PS1 mice

-

Improve the ability of learning, memory and spatial exploration, and reduce the deposition of SPs in brain of AD model mice, and reduce the expressions of APP and BACE1, increase the expression of IDE protein

[247]

28

EA

GV20, GV29

2 Hz,0.1 mA

SAMP8

IL-1β, IL-6, TNF-α

inhibit the peripheral and central nerve system inflammatory response by balancing the gut microbiota

[188]

29

MA

GV20, GV29

Each needle was rotated bidirectionally within 90° at a speed of 180°/s

SAMP8

-

Increase in CBF in the prefrontal lobe and hippocampu

[248]

30

EA

GV20, BL23

20 min, 2/3/50 Hz,1 mA

Aβ1-42-induced AD rat model

GSK-3β

Inhibition of GSK-3β activity

[176]

31

EA

GV29, LI20

10 min, 15 Hz,1.5 mA

SAMP8

p38MAPK

Inhibited the phosphorylation of p38MAPK and the excessive activation of microglia (MG) in the hippocampus

[67]