title: Centella asiatica Attenuates Amyloid-β-Induced Oxidative Stress and Mitochondrial Dysfunction.
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.
authors: Department of Neurology, Oregon Health and Science University, Portland, OR, USA.
authors: Nora E
authors: NE
authors: Gray
authors: Oregon Institute of Occupational Health Science, Oregon Health and Science University, Portland, OR, USA.
authors: Harini
authors: H
authors: Sampath
authors: Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR, USA.
authors: Jonathan A
authors: JA
authors: Zweig
authors: Department of Neurology, Oregon Health and Science University, Portland, OR, USA Department of Neurology and Parkinson's Disease Research Education and Clinical Care Center (PADRECC), Portland Veterans Affairs Medical Center, Portland, OR, USA.
authors: Joseph F
authors: JF
authors: Quinn
authors: Department of Neurology, Oregon Health and Science University, Portland, OR, USA.
authors: Amala
authors: A
authors: Soumyanath
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D028041:Centella / Q000737:chemistry; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D010446:Peptide Fragments / Q000633:toxicity*; D010936:Plant Extracts; D013997:Time Factors; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; C526146:Centella asiatica extract; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010936:Plant Extracts; D014315:Triterpenes; C074636:amyloid beta-protein (25-35); D000255:Adenosine Triphosphate; D002118:Calcium
keywords: Amyloid-β toxicity; Centella asiatica; calcium homeostasis; mitochondrial dysfunction; neuroprotection; reactive oxygen species
references: Cytotechnology. 2011 Mar;63(2):191-200
references: 21424281
references: Neurol Sci. 2013 Aug;34(8):1403-9
references: 23224641
references: J Food Sci. 2011 Mar;76(2):C250-6
references: 21535743
references: PLoS One. 2013;8(9):e74203
references: 24069280
references: J Neurochem. 2013 Apr;125(2):303-13
references: 23383735
references: Pharmacol Res. 2007 Dec;56(6):493-502
references: 17977008
references: Arch Neurol. 2003 Aug;60(8):1119-22
references: 12925369
references: Neurosci Lett. 2001 Feb 2;298(2):135-8
references: 11163296
references: Clin Exp Pharmacol Physiol. 2003 May-Jun;30(5-6):336-42
references: 12859423
references: J Asian Nat Prod Res. 2013 Sep;15(9):1013-22
references: 23909924
references: Am J Physiol Cell Physiol. 2007 Jan;292(1):C125-36
references: 16971499
references: Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18670-5
references: 20937894
references: J Neurosci. 2003 Mar 15;23(6):2212-7
references: 12657680
references: Neuromolecular Med. 2004;5(2):147-62
references: 15075441
references: J Submicrosc Cytol. 1985 Jul;17(3):459-64
references: 2991550
references: Neurodegener Dis. 2008;5(3-4):157-9
references: 18322377
references: Recent Pat Endocr Metab Immune Drug Discov. 2011 Jan;5(1):33-49
references: 22074576
references: J Neurosci. 2011 Nov 2;31(44):15703-15
references: 22049413
references: Pharmacol Biochem Behav. 2003 Feb;74(3):579-85
references: 12543222
references: Science. 1990 Oct 12;250(4978):279-82
references: 2218531
references: Am J Physiol Cell Physiol. 2004 Oct;287(4):C817-33
references: 15355853
references: J Neural Transm (Vienna). 2004 Mar;111(3):427-39
references: 14991463
references: Mol Chem Neuropathol. 1996 Oct-Dec;29(2-3):153-68
references: 8971693
references: Pharm Biol. 2013 Jan;51(1):30-5
references: 23134284
references: Exp Gerontol. 2012 Nov;47(11):878-86
references: 22824543
references: Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):486-91
references: 24297907
references: Hum Mol Genet. 2011 Jul 1;20(13):2495-509
references: 21459773
references: Cell Mol Neurobiol. 2014 Mar;34(2):227-34
references: 24263411
references: Mech Ageing Dev. 1996 Feb 24;86(2):105-14
references: 8852931
references: Mol Neurobiol. 2012 Aug;46(1):186-93
references: 22833458
references: Curr Alzheimer Res. 2013 May 1;10(4):390-405
references: 23545067
references: Free Radic Biol Med. 2011 Dec 1;51(11):2007-17
references: 21945098
references: Ann N Y Acad Sci. 2005 Nov;1056:474-85
references: 16387710
references: Cell Mol Neurobiol. 2009 Sep;29(6-7):1063-71
references: 19350381
references: Nat Prod Commun. 2012 Jul;7(7):841-3
references: 22908561
references: Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3270-4
references: 8159737
references: J Alzheimers Dis. 2014;40(2):359-73
references: 24448790
references: J Ethnopharmacol. 2008 Mar 5;116(2):325-32
references: 18191355
references: CNS Neurol Disord Drug Targets. 2012 Nov 1;11(7):926-32
references: 22998137
references: Biomed Pharmacother. 2004 Jan;58(1):39-46
references: 14739060
references: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14670-5
references: 19667196
references: Naunyn Schmiedebergs Arch Pharmacol. 2014 Jan;387(1):75-85
references: 24071813
references: Environ Toxicol Pharmacol. 2011 Sep;32(2):146-54
references: 21843793
references: Int J Alzheimers Dis. 2012;2012:381974
references: 22506133
references: J Neurosci. 2010 Feb 17;30(7):2636-49
references: 20164348
references: Neurotoxicology. 2008 Nov;29(6):948-57
references: 18930762
references: Nat Protoc. 2006;1(5):2406-15
references: 17406484
references: J Agric Food Chem. 2012 Sep 26;60(38):9631-41
references: 22946519
references: J Neurosci. 2001 May 1;21(9):3017-23
references: 11312286
references: J Alzheimers Dis. 2010;20 Suppl 2:S609-31
references: 20463406