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

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.

Berberine for prevention of dementia associated with diabetes and its comorbidities: A systematic review

“…Mechanistically, berberine reduced oxidative stress in the brain by increasing the levels of antioxidants, including glutathione, glutathione peroxidase and superoxide dismutase (SOD) [28,35,37], reduced AChE expression levels [28] and AChE activity at as low as 0.44-6 µmol/L half maximal inhibitory concentration [30,33,36,41] and uncompetitively inhibited indoleamine 2,3-dioxygenase [32], the first rate-limiting enzyme of kynurenine pathway, thereby potentially reducing the accumulation of neurotoxic metabolites involved in AD pathogenesis [146][147][148]. Berberine reduced Aβ generation in Swedish mutant amyloid precursor (APP)-expressing cells [31] and suppressed the Aβ-induced inflammatory response in microglia [42]. In addition, berberine reduced hyperphosphorylation of tau and APP [29,39], possibly through inactivation of GSK3β via Akt signaling [29].…”

Berberine: Pathways to protect neurons

“…Classical or widely acknowledged pathways such as the survival and apoptosis pathways (Simoes, Frozza, Hoppe, Menezes, & Salbego, ) have already proved to be involved in vitro or in vivo model of brain ischemia and reperfusion. Others such as p53/cyclin D1 (Chai et al, ), SPHK1/S1P signaling pathway (Luo et al, ), and ERK1/2 pathway (Zhu et al, ) are shown to serve as an integral part of neuroprotection in different animal models when preconditioned with BBR.…”

Berberine Inhibits the Release of Glutamate in Nerve Terminals from Rat Cerebral Cortex

“…Berberine has been confirmed to penetrate the blood-brain barrier [46] and possess neuroprotective activity both in animal and cell culture models of neurotoxicity such as ischaemia and Alzheimer's disease [5], [6], [7], [8], [47]. The exact mechanism responsible for the neuroprotective effect of berberine remains to be further clarified.…”