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Table 1 Basic information of included studies

From: Neuroprotective effects of berberine in animal models of Alzheimer’s disease: a systematic review of pre-clinical studies


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.


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

  1. MWM, Morris water maze; WB analysis, Western Blot analysis; PET, Positron-Emission Tomography; RT-PCR, Reverse Transcription Polymerase Chain Reaction; AchE, Acethyl-cholinesterase; ICV-STZ, Intracerebroventricular streptozotocin; GSH, glutathione; Pilo, pilocarpine;