Background
Method
Literature search
Inclusion/exclusion criteria and screening
Inclusion criteria
Exclusion criteria
Data extraction and quality assessment
Data extraction
Results
Study | Animal Models | Administration(dosage, time and route) | Evaluation methods of the treatment effectiveness test |
---|---|---|---|
He et al. [17] | Thirty 120-day APP/PS1 mice (male, 30) | 0, 50 and 100 mg/kg-berberine (n = 10 for each group), intragastric administration for 14 days. | MWM, WB analysis, immunohistochemistry |
Chen et al. [18] | Aged 4–5 weeks Wistar rats weighting about 200 g memory-impairment diabetic Wistar Rats model (male) | DM group (diabetes mellitus), berberine group (187.75 mg/kg/d) and Met group (Metformin, 184 mg/kg/d), orally administration for 2 weeks. | Fear Condition, PET, WB analysis, immunochemistry |
Huang et al. [19] | 4-month 3 × Tg-AD (male,18;female,18) | 0, 50 and 100 mg/kg berberine (n = 12 for each group), orally administration for 4 months. | MWM, platform recognition, HVS water maze, Aβ1–42: Elisa, WB analysis, Immunofluorescence staining, histological analysis |
Oliveira et al. [20] | 300–350 g ICV-STZ induce sporadic Alzheimer’s-like dementia Wistar rats model (male, 60) | Control (CTR), berberine 50 mg/kg, berberine 100 mg/kg, streptozotocin, streptozotocin plus berberine 50 mg/kg, and streptozotocin plus berberine 100 mg/kg, orally administration for 21 days. | MWM, Elevated plus maze task, LDH: Labtest kit, AChE activity |
Patil et al. [21] | 200–250 g memory-impairment Wistar rats model induced by ethanol (male,12) | 25, 50 and 100 mg/kg berberine, vitamin C (100 mg/kg), and vehicle (1 mL/kg), DDW control rats(double distilled water), orally administration (chronic treatment: once a day for 45 days before training; acute treatment: once a day for 5 days during training). | MWM, Memory consolidation test, Elevated plus maze test, ChE activity |
Haghani et al. [22] | 200–250 g 60–65 days Aβ infused Wistar rats model (male, 32) | Sham(normal saline), berberine(50 mg/kg), Aβ(normal saline)and Aβ + berberine(berberine 50 mg/kg) (n = 8 rats in each group), intraperitoneal administration daily for 13 days. | MWM, Passive avoidance test, |
Zhan et al. [23] | 180–220 g, 10–12 weeks D-galactose-induced memory impairment Wistar rats (male) | Berberine (100 mg/kg per day), orally administration for 7 weeks. | MWM, WB analysis, RT-PCR |
Gao et al. [24] | 200–250 g (Pilo)-induced epilepsy Sprague Dawley rats (male,104) | 1) control group (n = 12), saline; 2) berberine 100 mg/kg group (n = 12); 3) Pilo group (n = 20); 4) Pilo + berberine 25 mg/kg group (n = 20); 5) Pilo + berberine 50 mg/ kg group (n = 20); 6) Pilo + berberine 100 mg/ kg group (n = 20). Orally administration daily for 7 days before Pilo injection. | MWM, GSH level: sectrophotometrical |
Moghaddam et al. [25] | (STZ)-diabetic Wistar rats (male,50) | Control, berberine-treated control (100 mg/kg;), diabetic, and berberine-treated diabetics (50 and 100 mg/kg respectively). | Y-maze, Single-trial passive avoidance test, Electrophysiological experiments |
Durairajan et al. [15] | TgCRND8 mice | Berberine (25 mg/kg per day), berberine (100 mg/kg per day), orally administeration | MWM, ELISA, Immunohistochemistry, WB analyses |
Lee et al. [26] | 260–280 g SCO-induced memory deficits SD rats (male) | SAL group, PA group, SCO-induced and saline-treated group, SCO + berberine20 mg/kg group,SCO + PA100 group, SCO-induced plus 200 mg/kg PA-treated group, and the SCO-induced plus 0.2 mg/kg TA-treated group. Intraperitoneally administration once a day for 14 days. | MWM, Hidden platform trial, Probe trial, immunohistochemical, ELISA, |
Bhutada et al. [27] | Memory-impairment diabetic Wistar rats (male) | 1.berberine (25, 50, 100 mg/kg), vitamin C (100 mg/kg), metformin (500 mg/kg), or vehicle (1 mL/kg) twice daily for 30 days. Orally administration 2.berberine (25, 50, 100 mg/kg), vitamin C (100 mg/kg), metformin (500 mg/kg), vehicle (1 mL/kg), twice daily during training trials for next 5 days. Orally administration | MWM, Memory consolidation test, Open field test |
Lim et al. [28] | Ibotenic acid-induced memory deficient Sprague Dawley rat model (male) | IBO model(saline), IBO model(berberine), saline injected sham group(berberine), daily Intraperitoneally administration for a week. | immunohistochemistry |
Zhu et al. [29] | injected A-beta (1–40) (5 microgram) AD rat model | Berberine chloride (50 mg/kg), Orally administration once daily for 14 days. | MWM, immunohistochemistry, PCR |
Peng et al. [30] | 200–250 g SCOP-induced amnesia Sprague-Dawley rats (male) | Berberine (0.1 and 0.5 g/kg) orally daily for 7-day or 14-day. | Passive avoidance response task, Motor activity measurements |
Methodological quality
Study | A | B | C | D | E | F | Total |
---|---|---|---|---|---|---|---|
He et al. [20] | √ | √ | √ | √ | √ | 5 | |
Chen et al. [27] | √ | √ | √ | √ | 4 | ||
Huang et al. [21] | √ | √ | √ | √ | √ | 5 | |
Oliveira et al. [19] | √ | √ | √ | √ | √ | 5 | |
Patil et al. [17] | √ | √ | √ | √ | 4 | ||
Haghani et al. [31] | √ | √ | √ | √ | √ | 5 | |
Zhan et al. [32] | √ | √ | √ | √ | 4 | ||
Gao et al. [22] | √ | √ | √ | √ | √ | 5 | |
Moghaddam et al. [23] | √ | √ | √ | √ | 4 | ||
Durairajan et al. [15] | √ | √ | √ | √ | √ | 5 | |
Lee et al. [33] | √ | √ | √ | 3 | |||
Bhutada et al. [34] | √ | √ | √ | 3 | |||
Lim et al. [24] | √ | √ | √ | √ | 4 | ||
Zhu et al. [25] | √ | √ | √ | √ | 4 | ||
Peng et al. [28] | √ | √ | √ | √ | 4 |
Anti-Alzheimer’s disease mechanisms of berberine
Study | Anti-AD effects | Neuroprotection mechanism |
---|---|---|
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. |