Neuroprotective effect of berberine chloride on cognitive impairment and hippocampal damage in experimental model of vascular dementia

Abstract

Objectives: The major objective of the present study was to investigate the potential neuroprotective effect of berberine chloride on vascular dementia. Berberine, as an ancient medicine in China and India, is the main active component derived from the Berberis sp. Several studies have revealed the beneficial effects of berberine in various neurodegenerative disorders.

Materials and methods: To induce vascular dementia, chronic bilateral common carotid artery occlusion was performed on male Wistar rats. After surgery, the rats were treated daily by oral administration of berberine chloride (50 mg/kg) for two months. The cognition function of treated rats, were evaluated by Morris Water Maze (MWM) test. In addition, Nissl and TUNEL staining were chosen to assess neuronal damage within the hippocampal CA1 area.

Results: It was obvious that chronic cerebral hypoperfusion (CCH), caused cognitive impairment and neuronal damages within CA1 hippocampal subregion. Berberine chloride was able to prevent cognitive deficits, (P<0.05) and reversed CCH-induced hippocampal neuronal loss and apoptosis, (P<0.05).

Conclusion: Berberine chloride may be considered as a potential treatment for cognitive deficits and neuronal injury caused by CCH in the hippocampal CA1 area.

Keywords: Apoptosis; Berberine; Hippocampus; Memory; Vascular dementia.

Figure 1

Escape latency in morris water maze test (mean±SE, n=8) in the different groups. Statistical analysis was performed using two-way analysis of variance (ANOVA) with repeated measures followed by the bonferronipost test. **P<0.01 vs. SH group. #P<0.05 vs. CCH group (Ctr= Control, SH=Sham, CCH= Chronic Cerebral Hypoperfusion, BBR= Berberine)

Figure 2

Traveled distance in Morris water maze test (mean±SE, n=8) in the different groups. Statistical analysis was performed using two-way analysis of variance (ANOVA) with repeated measures followed by the bonferroni post test.*P<0.05 vs. SH group. #P<0.05 vs. CCH group. (Ctr= Control, SH=Sham, CCH= Chronic Cerebral Hypoperfusion, BBR= Berberine)

Figure 3

Time spent in target quadarant in Morris water maze test (mean±SE, n=8) in the different groups. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by the tukeypost test. **P<0.01 vs. sham SH group. #P<0.05 vs. CCH group (Ctr= Control, SH=Sham, CCH= Chronic Cerebral Hypoperfusion, BBR= Berberine)

Figure 4

TUNEL staining of hippocampal CA1 region. A: control group (Ctr), B: Sham (SH) group, C: Chronic Cerebral Hypoperfusion (CCH) group, D: Berberine (BBR) group and E: CCH + BBR group. Black arrows indicate intact cells and red arrows indicate apoptotic cells (magnification ×400)

Figure 5

The percentage of apoptotic to total cells (Apoptotic index) (mean±SE, n=4) in the hippocampal CA1 subfield in the different groups. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by the tukey post test. ***P<0.001 and *P<0.05 vs. SH group. ^#P<0.05 vs. CCH group. (Ctr= Control, SH=Sham, CCH= Chronic Cerebral Hypoperfusion, BBR= Berberine)

Figure 6

Nissl staining of hippocampal CA1 region. A: control group (Ctr), B: Sham (SH) group, C: Chronic Cerebral Hypoperfusion (CCH) group, D: Berberine (BBR) group, E: CCH+BBR group. Black arrows indicate intact cells and red arrows indicate necrotic cells (magnification ×400)

Figure 7

Neuronal density (mean±SE, n=4) in the hippocampal CA1 subfield in the different groups. Statistical analysis was performed using one-way analysis of variance (ANOVA) followed by the tukey post test. **P<0.01 vs. SH group. ^#P<0.05 vs. CCH group (Ctr= Control, SH=Sham, CCH= Chronic Cerebral Hypoperfusion, BBR= Berberine)