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

Ying Ma,Fujun Wu,Feiqi Zhu,Zhong Pei,Guangjian Liu,Zhong Li,Yong'An Sun

doi:10.1186/1471-2202-12-125

Abstract

BackgroundBerberine (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-amyloid40/42, which plays a critical and primary role in the pathogenesis of Alzheimer's disease. However, the mechanism by which it accomplishes this remains unclear.ResultsHere, we report that BER could not only significantly decrease the production of beta-amyloid40/42 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-amyloid40/42 and the expression of BACE.ConclusionOur data indicate that BER decreases the production of beta-amyloid40/42 by inhibiting the expression of BACE via activation of the ERK1/2 pathway.

Highlights

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
BER and U0126 showed no significant effects on the release of Lactate dehydrogenase (LDH) in the culture medium (P > 0.05) (Figure 1D, E and 1F), but 3% H2O2 significantly increased the release of LDH in the culture medium (P < 0.01)
Effects of BER and U0126 on the production of Ab40/42 We assayed the treatments on the extracellular Ab40/42 levels in the medium cultured from HEK293 cells by sandwich enzyme-linked immunosorbent assay (ELISA)

Summary

Introduction

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 been demonstrated that BER can reduce the production of beta-amyloid40/42, which plays a critical and primary role in the pathogenesis of Alzheimer’s disease. Some nonsteroidal anti-inflammatory drugs (NSAIDs), including sulindac sulfide, S-ibuprofen, R-ibuprofen and indomethacin, have been shown to inhibit the production of Ab40/42 by inhibiting the expression of BACE and the activity of g-secretase via activating peroxisome proliferator-activated receptor g (PPAR g) and inhibiting Rho-Rho associated kinase (Rho-ROCK) pathway [5,6]. Some statins, including sinvastatin, rosuvastatin, and lovastatin, the cholesterol-lowering drugs, have been found to reduce levels of Ab40/42 by promoting the expression of a-secretase and inhibiting BACE activity [7,8,9]

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