Centella asiatica Attenuates Amyloid-β-Induced Oxidative Stress and Mitochondrial Dysfunction

Nora E. Gray, Harini Sampath, Jonathan A. Zweig, Joseph F. Quinn, Amala Soumyanath

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Background: We previously showed that a water extract of the medicinal plant Centella asiatica (CAW) attenuates amyloid-β (Aβ)-induced cognitive deficits in vivo, and prevents Aβ-induced cytotoxicity in vitro. Yet the neuroprotective mechanism of CAW is unknown. Objective: The goal of this study was to identify biochemical pathways altered by CAW using in vitro models of Aβ toxicity. Methods: The effects of CAW on aberrations in antioxidant response, calcium homeostasis, and mitochondrial function induced by Aβ were evaluated in MC65 and SH-SY5Y neuroblastoma cells. Results: CAW decreased intracellular reactive oxygen species and calcium levels elevated in response to Aβ, and induced the expression of antioxidant response genes in both cell lines. In SH-SY5Y cells, CAW increased basal and maximal oxygen consumption without altering spare capacity, and attenuated Aβ-induced decreases in mitochondrial respiration. CAW also prevented Aβ-induced decreases in ATP and induced the expression of mitochondrial genes and proteins in both cell types. Caffeoylquinic acids from CAW were shown to have a similar effect on antioxidant and mitochondrial gene expression in neuroblastoma cells. Primary rat hippocampal neurons treated with CAW also showed an increase in mitochondrial and antioxidant gene expression. Conclusions: These data suggest an effect of CAW on mitochondrial biogenesis, which in conjunction with activation of antioxidant response genes and normalizing calcium homeostasis, likely contributes to its neuroprotective action against Aβ toxicity.

Original languageEnglish (US)
Pages (from-to)933-946
Number of pages14
JournalJournal of Alzheimer's Disease
Volume45
Issue number3
DOIs
StatePublished - Jan 1 2015

Keywords

  • Amyloid-β toxicity
  • Centella asiatica
  • calcium homeostasis
  • mitochondrial dysfunction
  • neuroprotection
  • reactive oxygen species

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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