Decrease in the production of beta-amyloid by berberine inhibition of the expression of beta-secretase in HEK293 cells
1 Neurology department of the affiliated Yuebei people's hospital, Shantou University Medical College. Shaoguan city, Guangdong Province, 512026, China
2 Neurology department of Taihe hospital, the affiliated hospital of Hubei University of Medicine. Shiyan city, Hubei Province, 442000, China
3 College of life Sciences Anhui Agricultural University, Hefei, Anhui, 230036, China
4 Cardiology department of the affiliated Yuebei people's hospital, Shantou University Medical College. Shaoguan city, Guangdong Province, 512026, China
5 Neurology department of the first affiliated hospital, Sun Yat-Sen University, Guangzhou city, Guangdong Province, 510080, China
6 Neurology department of Peking University first hospital, Beijing, 100034, China
BMC Neuroscience 2011, 12:125 doi:10.1186/1471-2202-12-125Published: 12 December 2011
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-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.
Here, 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.
Our data indicate that BER decreases the production of beta-amyloid40/42 by inhibiting the expression of BACE via activation of the ERK1/2 pathway.