Araucaria angustifolia (Bertol.) Kuntze has neuroprotective action through mitochondrial modulation in dopaminergic SH-SY5Y cells

Mol Biol Rep. 2019 Dec;46(6):6013-6025. doi: 10.1007/s11033-019-05037-6. Epub 2019 Aug 26.

Abstract

Brain disorders (BD) including neuropsychiatric and neurodegenerative diseases, are often associated with impairments in mitochondrial function and oxidative damage that can lead to neuronal injury. The mitochondrial complex I enzyme is one of the main sites of ROS generation and is implicated in many BD pathophysiologies. Despite advances in therapeutics for BD management, conventional pharmacotherapy still cannot efficiently control neuronal redox imbalance and mitochondrial dysfunction. Araucaria angustifolia is one of the main pine species in South America and presents a notable therapeutic history in folk medicine. A. angustifolia extract (AAE), obtained from the natural waste named bracts, is rich in flavonoids; molecules able to regulate cell redox metabolism. We examined the effects of AAE on rotenone-induced mitochondrial complex I dysfunction in human dopaminergic SH-SY5Y cells. AAE restored complex I assembly and activity mainly through overexpression of NDUFS7 protein and NDUFV2 gene levels. These findings were accompanied by a reduction in the generation of neuronal reactive oxygen species and lipid peroxidation. Our data demonstrates, for the first time, that AAE exerts in vitro neuroprotective effects, thus making it an interesting source for future drug development in BD-associated mitochondrial dysfunctions.

Keywords: Araucaria angustifolia; Complex I; Polyphenols; Redox imbalance; Rotenone.

MeSH terms

  • Apoptosis / drug effects
  • Araucaria / genetics
  • Araucaria / metabolism*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Electron Transport Complex I / drug effects*
  • Humans
  • Lipid Peroxidation / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / metabolism
  • Neurons / metabolism
  • Neuroprotection
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Rotenone / pharmacology
  • Seeds / metabolism*
  • South America

Substances

  • Neuroprotective Agents
  • Plant Extracts
  • Reactive Oxygen Species
  • Rotenone
  • Electron Transport Complex I