In silico, In vitro, and In vivo Evaluation of the Anti-alzheimer’s Activity of Berberine

Louise   T.   Theunis; Junie   B.   Billones; Chung-Der      Hsiao; Oliver   B.   Villaflores; Agnes   L.   Llamasares-Castillo

doi:10.2174/0115734080306283240719110244

Abstract

Background: Alzheimer’s disease (AD), a progressive neurodegenerative disease for which there is no effective cure is among the leading causes of death worldwide.

Objectives: To investigate the potential anti-AD activity of berberine (BBR).

Methods: In silico assessment included molecular docking and ADMET prediction. BBR’s in vitro inhibitory activity of the target selected from docking results was assessed via colorimetric inhibitor screening assay. BBR’s LC₅₀ in adult zebrafish was determined via an Acute Toxicity Study. ZnCl₂ concentration for AD induction was determined via toxicity study and T-maze test. Finally, zebrafish were treated with ZnCl₂ alone or simultaneously with either BBR or donepezil and assessed via the inhibitory avoidance task, followed by ELISA of AD-related biomarker levels in brain tissue.

Results: The in silico assessment showed BBR’s desirable drug properties and binding affinity on selected AD-related targets, which was the greatest docking score with AChE. The in vitro IC₅₀ on AChE was 3.45 μM. The LC₅₀ in adult zebrafish was calculated at 366 ppm. In the T-maze test, ZnCl₂ at 2.5 ppm caused the greatest cognitive impairment accompanied by moderate freezing. In the inhibitory avoidance test, fish treated with either 100 ppm BBR or 2.5 ppm donepezil had significantly better performance than ZnCl₂-treated fish. ZnCl₂-treated zebrafish brain tissue had the highest Aβ levels and AChE activity of all groups, but these were significantly lower in donepeziland BBR-treated fish. ZnCl₂- and donepezil-treated fish had similar TNF-α levels, whereas BBR treatment significantly lowered them close to those of untreated fish.

Conclusion: BBR showed anti-amyloidogenic, anti-AChE, and anti-inflammatory effects, which support its potential use in AD therapy.

Keywords: Acetylcholinesterase inhibition, Alzheimer’s disease, berberine, inhibitory avoidance, tumor necrosis factor-alpha inhibition, zebrafish, beta-amyloid, autodock vina.

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DOI https://dx.doi.org/10.2174/0115734080306283240719110244	Print ISSN 1573-4080
Publisher Name Bentham Science Publisher	Online ISSN 1875-6662

Current Enzyme Inhibition

In silico, In vitro, and In vivo Evaluation of the Anti-alzheimer’s Activity of Berberine

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