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Background  Berberine (BER), the major alkaloidal component of  Rhizoma coptidis , has multiple pharmacological effects including inhibition of acetylcholinesterase, reduction of cholesterol and glucose levels, anti-inflammatory, neuroprotective and neurotrophic effects. It has also been demonstrated that BER can reduce the production of beta-amyloid 40/42 , which plays a critical and primary role in the pathogenesis of Alzheimer's disease. However, the mechanism by which it accomplishes this remains unclear.    Results  Here, we report that BER could not only significantly decrease the production of beta-amyloid 40/42  and the expression of beta-secretase (BACE), but was also able to activate the extracellular signal-regulated kinase1/2 (ERK1/2) pathway in a dose- and time-dependent manner in HEK293 cells stably transfected with APP695 containing the Swedish mutation. We also find that U0126, an antagonist of the ERK1/2 pathway, could abolish (1) the activation activity of BER on the ERK1/2 pathway and (2) the inhibition activity of BER on the production of beta-amyloid 40/42  and the expression of BACE.    Conclusion  Our data indicate that BER decreases the production of beta-amyloid 40/42  by inhibiting the expression of BACE via activation of the ERK1/2 pathway.

Decrease in the production of beta-amyloid by berberine inhibition of the expression of beta-secretase in HEK293 cells