Background: Berberine (BBR) has neuroprotective effects on many brain diseases, including
Alzheimer’s disease (AD). Amyloid -beta (Aβ) senile plaque is the most classical pathological
hallmarks of AD. Aβ produces from a sequential cleavage by β-secretase (beta-site amyloid precursor
protein cleaving enzyme 1, BACE1) and γ -secretase. The aim of our work was to investigate
whether the neuroprotective effects of BBR on AD is related to inhibiting Aβ pathology.
Method: The cognitive function of mice was assessed by the Morris water maze (MWM) test.
The Aβ levels were determined by enzyme linked immunosorbent assay; the expression of APP,
sAPPα, ADAM10 and ADAM17, sAPPβ and BACE1 was detected by Western blotting; and the activity
of γ -secretase complex (NCT, PS1, Aph-1α and Pen-2) was determined by Western blotting and
Results: BBR improved learning and memory deficits of APP/PS1 mice. BBR decreased Aβ levels in
the hippocampus of APP/PS1 mice. BACE1 and sAPP -β levels in the BBR-treated groups were significantly
reduced in the hippocampus of AD mice. BBR markedly decreased the expression of PS1,
Aph-1α and Pen-2, but had no effect on NCT. The levels of sAPPα, ADAM10 and ADAM17 in the
hippocampus of BBR-treated mice significantly increased, compared with the control ones (P<0.05).
Conclusion: BBR inhibits the activity of β/γ-secretases, enhances α-secretases, and lowers the Aβ level
in the hippocampus of AD mice, and improves Alzheimer’s-like cognitive impairment.