title: Decrease in the production of β-amyloid by berberine inhibition of the expression of β-secretase in HEK293 cells.
abstract: 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-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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Neurology Department of the Affiliated Yuebei People's Hospital, Shantou University Medical College, Shaoguan city, Guangdong Province, 512026, China. zfqzsu2004@yahoo.com.cn
authors.forename: Feiqi
authors.initials: F
authors.lastname: Zhu
authors.forename: Fujun
authors.initials: F
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Ma
authors.forename: Guangjian
authors.initials: G
authors.lastname: Liu
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.forename: Yong'an
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhong
authors.initials: Z
authors.lastname: Pei
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors / Q000235:genetics; D001599:Berberine / Q000494:pharmacology*; D002070:Butadienes / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology; D009570:Nitriles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002070:Butadienes; D018696:Neuroprotective Agents; D009570:Nitriles; D010446:Peptide Fragments; C113580:U 0126; C075222:amyloid beta-protein (1-42); D001599:Berberine; D053829:Amyloid Precursor Protein Secretases