Table 3 Anti-AD effects and underlying mechanisms after berberine treatment of included studies

He et al. [17]

1. Mitigated cognitive impairment of AD mice.

2. Inhibited phosphorylation of Tau.

3. Limited lipid peroxidation.

4. Lowered the levels of IL-1b and TNF-a.

5. Lowered the levels of both GFAP and CD45.

Anti-inflammatory, suppressed NF-kB signaling pathway, anti-oxidative stress and anti-apoptosis.

Chen et al. [18]

1. Inhibited the inflammation mediator release and insulin resistance in the mPFC of diabetic rats.2. Ameliorated cognitive impairment and accelerates the reinforcement of the information.

3. Decreased the expressions of amyloid precursor protein and BACE-1, and the production of oligomeric Aβ42.

Inhibits the PI3K/Akt/mTOR and MAPK signaling pathway, as well as two novel isoforms PKCη and PKCε and the translocation of NF-κB

Anti-inflammatory. Anti-amyloid.

Huang et al. [19]

1. Ameliorated cognitive deficits, improved spatial learning capacity and memory retention in 3 × Tg-AD mice model2. Reduced the production of Aβ and BACE1 protein level in primary hippocampal neurons and the brains of 3 × Tg-AD mice

Anti-amyloid, enhancing autophagy through the class III PI3K/beclin-1 pathway. Anti-apoptosis.

Oliveira et al. [20]

1. Prevented the memory loss, anxiogenic behavior

2. Reduced escape latency in ICV-STZ rats

3. Reduced the number of dead cells in both the hippocampus and cerebral cortex in STZ rat.

4. Decreased AChE activity in both the hippocampus and cerebral cortex of ICV-STZ rat.

ChE inhibition.

Patil et al. [21]

1. Improved ethanol-induced memory impairment.

2. Lowered oxidative stress and ChE activity in ethanol treated rats.

Anti-oxidant and ChE inhibition.

Haghani et al. [22]

1. Prevented the impairing impacts of Aβ on the learning, memory and electrophysiological properties of the CA1 pyramidal neurons.

2. Improved the memory performance.

3. Restored the Aβ-induced impairments in the firing frequency, half-width and rebound action potential.

Phenomenon research.

Zhan et al. [23]

1. Rescued D-galactose-induced memory impairment the mRNA and protein levels of Arc/Arg3.12. Reversed the synaptic deficits induced by D-galactose.

Phenomenon research.

Gao et al. [24]

1. Relieved pilocarpine-induced convulsions in rats.

2. Reduced the degree of oxidative stress in the hippocampus.3. Attenuated memory impairment.

4. alleviated neuronal degeneration in hippocampal CA1 region in SE rats.

Anti-oxidant.

Moghaddam et al. [25]

1. Ameliorated learning and memory impairment.2. Restored PS amplitude and fEPSP and ameliorated learning and memory impairment and attenuated apoptosis of pyramidal neurons in the CA1 area.

Anti-apoptosis.

Durairajan et al. [15]

1. Lower Aβ levels, alleviated cognitive deficits and amyloid neuropathology, reduce gliosis.

2. Reduced the Aβ and CTFs, probably by downregulating the phosphorylation of APP and of CTFs via the activation of the PI3K/Akt/GSK3 pathway.

3. Reduced the cognitive impairment

4. Decreased Aβ plaques of all 3 size subsets (25, 25–50, and > 50 μm).

5. Reduced vascular amyloids as well as parenchymal amyloids

6. Reducing ThioS-positive vascular amyloids.

7. 45% reduction in microgliosis and a 54% decrease in astrocytosis

Anti-amyloid, activation of the PI3K/Akt/GSK3 pathway

Lee et al. [26]

1. Improved memory impairment and reduced the escape latency.2. Alleviated memory-associated decreases and restored brain-derived neurotrophic factor and cAMP-response element-binding protein mRNA expression in the hippocampus.3. Decreases the expression of proinflammatory cytokines mRNA in the hippocampus.

Anti-inflammatory.

Bhutada et al. [27]

1. Improved cognitive performance.

2. Lowered hyperglycemia, oxidative stress, and ChE activity in diabetic rats.

Anti-oxidant. ChE inhibition.

Lim et al. [28]

1. Increased neuronal cells immunoreactive to calbindin in the hippocampus and entorhinal cortex area.

2. Hippocampal cells were increased in the pyramidal layer of CA1 region and dentate gyrus

Phenomenon research.

Zhu et al. [29]

Ameliorates the spatial memory impairment.

Phenomenon research.

Peng et al. [30]

Improved SCO-induced amnesia

Phenomenon research.