In vitro evaluation of the protective effects of plant extracts against amyloid-beta peptide-induced toxicity in human neuroblastoma SH-SY5Y cells

PLoS One. 2019 Feb 14;14(2):e0212089. doi: 10.1371/journal.pone.0212089. eCollection 2019.

Abstract

Alzheimer's disease (AD) is the most common form of dementia and has no cure. Therapeutic strategies focusing on the reduction of oxidative stress, modulation of amyloid-beta (Aβ) toxicity and inhibition of tau protein hyperphosphorylation are warranted to avoid the development and progression of AD. The aim of this study was to screen the crude extracts (CEs) and ethyl-acetate fractions (EAFs) of Guazuma ulmifolia, Limonium brasiliense, Paullinia cupana, Poincianella pluviosa, Stryphnodendron adstringens and Trichilia catigua using preliminary in vitro bioassays (acetylcholinesterase inhibition, antioxidant activity and total polyphenol content) to select extracts/fractions and assess their protective effects against Aβ25-35 toxicity in SH-SY5Y cells. The effect of the EAF of S. adstringens on mitochondrial membrane potential, lipid peroxidation, superoxide production and mRNA expression of 10 genes related to AD was also evaluated and the electropherogram fingerprints of EAFs were established by capillary electrophoresis. Chemometric tools were used to correlate the in vitro activities of the samples with their potential to be evaluated against AD and to divide extracts/fractions into four clusters. Pretreatment with the EAFs grouped in cluster 1 (S. adstringens, P. pluviosa and L. brasiliense) protected SH-SY5Y cells from Aβ25-35-induced toxicity. The EAF of S. adstringens at 15.62 μg/mL was able completely to inhibit the mitochondrial depolarization (69%), superoxide production (49%) and Aβ25-35-induced lipid peroxidation (35%). With respect to mRNA expression, the EAF of S. adstringens also prevented the MAPT mRNA overexpression (expression ratio of 2.387x) induced by Aβ25-35, which may be related to tau protein hyperphosphorylation. This is the first time that the neuroprotective effects of these fractions have been demonstrated and that the electropherogram fingerprints for the EAFs of G. ulmifolia, L. brasiliense, P. cupana, P. pluviosa and S. adstringens have been established. The study expands knowledge of the in vitro protective effects and quality control of the evaluated fractions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Amyloid beta-Peptides / toxicity*
  • Antioxidants / pharmacology*
  • Cell Line, Tumor
  • Cholinesterase Inhibitors / pharmacology*
  • Cytoprotection / drug effects
  • Gene Expression Regulation / drug effects
  • Humans
  • Lipid Peroxidation / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Neuroblastoma / pathology*
  • Neuroprotective Agents / pharmacology*
  • Plant Extracts / pharmacology*
  • Polyphenols / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Cholinesterase Inhibitors
  • Neuroprotective Agents
  • Plant Extracts
  • Polyphenols
  • RNA, Messenger
  • Reactive Oxygen Species
  • Acetylcholinesterase

Grants and funding

The authors are grateful to Brazilian agencies Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES - www.capes.gov.br), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq - www.cnpq.br), Financiadora de Estudos e Projetos (FINEP - www.finep.gov.br), Complexo de Centrais de Apoio à Pesquisa (COMCAP/UEM - www.comcap.uem.br), Fundação Araucária (www.fappr.pr.gov.br), and Instituto Nacional de Ciência e Tecnologia para Inovação Farmacêutica (INCT_if - http://inct.cnpq.br/web/inct-if) for their financial support and fellowships awarded to A. L. Sereia, M. T. de Oliveira, A. Baranoski, F. M. Ribeiro, R. G. Isolani, D. C. Medeiros, and D. Chierrito. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.