Role of berberine in Alzheimer's disease

Abstract

Berberine, an important protoberberine isoquinoline alkaloid, has several pharmacological activities, including antimicrobial, glucose- and cholesterol-lowering, antitumoral, and immunomodulatory properties. Substantial studies suggest that berberine may be beneficial to Alzheimer's disease (AD) by limiting the pathogenesis of extracellular amyloid plaques and intracellular neurofibrillary tangles. Increasing evidence has indicated that berberine exerts a protective role in atherosclerosis related to lipid- and glucose-lowering properties, implicating that berberine has the potential to inhibit these risk factors for AD. This review also attempts to discuss the pharmacological basis through which berberine may retard oxidative stress and neuroinflammation to exhibit its protective role in AD. Accordingly, berberine might be considered a potential therapeutic approach to prevent or delay the process of AD. However, more detailed investigations along with a safety assessment of berberine are warranted to clarify the role of berberine in limiting these risk factors and AD-related pathologies.

Keywords: amyloid; berberine; neuroinflammation; oxidative stress; risk factors; tau.

Figure 1

Possible mechanisms by which berberine modifies metabolism of APP. Notes: In the amyloidogenic pathway, cleavage of APP by β-secretase generates soluble N-terminal fragment (sAPPβ) and C-terminal fragment (C99). C99 can be cleaved by γ-secretase to yield the APP intracellular domain (AICD) and Aβ. In the nonamyloidogenic pathway, α-secretase cleaves APP, generating a soluble fragment of APP (sAPPα) and C-terminal fragment (α-CTF), which is further cleaved by γ-secretase releasing the p3 peptide and AICD. BBR could decrease β-secretase and γ-secretase and inhibit the process of amyloidogenic pathway, lowering the Aβ release and the formation of amyloid plaques. The role of BBR in α-secretase remains unclear in the nonamyloidogenic pathway. ? Represent that the mechanism is unclear. Abbreviations: BBR, berberine; Aβ, beta-amyloid; AICD, APP intracellular domain; APP, amyloid precursor protein; sAPP, soluble APP.