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

BMC Neuroscience

Zhong Pei¹  Yong'an Sun⁵  Zhong Li¹  Guangjian Liu⁴  Ying Ma²  Fujun Wu³  Feiqi Zhu⁴ 

[1] Neurology department of the first affiliated hospital, Sun Yat-Sen University, Guangzhou city, Guangdong Province, 510080, China;Cardiology department of the affiliated Yuebei people's hospital, Shantou University Medical College. Shaoguan city, Guangdong Province, 512026, China;College of life Sciences Anhui Agricultural University, Hefei, Anhui, 230036, China;Neurology department of Taihe hospital, the affiliated hospital of Hubei University of Medicine. Shiyan city, Hubei Province, 442000, China;Neurology department of Peking University first hospital, Beijing, 100034, China

关键词: extracellular signal-regulated kinase1/2;    beta-secretase;    beta-amyloid_40/42;    berberine;    Alzheimer's disease;   

Others  :  1170861
DOI  :  10.1186/1471-2202-12-125

 received in 2011-10-20, accepted in 2011-12-12,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Zhu et al; licensee BioMed Central Ltd.

【 图 表 】

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