Baicalein protects PC12 cells from Aβ25-35-induced cytotoxicity via inhibition of apoptosis and metabolic disorders

Life Sci. 2020 May 1:248:117471. doi: 10.1016/j.lfs.2020.117471. Epub 2020 Feb 26.

Abstract

Aims: This study aimed to explore the protective effects and possible mechanisms of baicalein on Aβ25-35-induced toxicity.

Main methods: Thioflavin-T (Th-T) dye was used to determine the effects of baicalein on Aβ25-35 aggregation in vitro. PC12 cells were stimulated with Aβ25-35, then the effects of baicalein on apoptosis, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), mitochondrial respiratory complex I, reactive oxygen species (ROS) and nitric oxide (NO) levels were determined. Moreover, LC-MS metabolomics approach was used to detect metabolic changes induced by baicalein in Aβ25-35-injured PC12 cells.

Key findings: The results showed that baicalein could inhibit the aggregation of Aβ25-35 in vitro. Furthermore, pretreatment with baicalein significantly prevented Aβ25-35-induced cell apoptosis, as manifested by increasing the levels of MMP, ATP and mitochondrial respiratory complex I, decreasing the contents of ROS and NO. LC-MS metabolomics revealed that baicalein can regulate 5 metabolites, mainly involving two metabolic pathways, arginine and proline metabolism, nicotinate and nicotinamide metabolism.

Significance: Our study revealed that baicalein has a protective effect on Aβ25-35-induced neurotoxicity in PC12 cells, which may be related to inhibition of apoptosis and metabolic disorders.

Keywords: Apoptosis; Aβ(25)(–)(35); Baicalein; LC-MS metabolomics.

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Apoptosis / drug effects*
  • Arginine / metabolism
  • Electron Transport Complex I / metabolism
  • Flavanones / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Neuroprotective Agents / pharmacology*
  • Niacin / metabolism
  • Niacinamide / metabolism
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects
  • PC12 Cells
  • Peptide Fragments / antagonists & inhibitors*
  • Peptide Fragments / toxicity
  • Proline / metabolism
  • Protein Aggregates / drug effects
  • Rats
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism

Substances

  • Amyloid beta-Peptides
  • Flavanones
  • Neuroprotective Agents
  • Peptide Fragments
  • Protein Aggregates
  • Reactive Oxygen Species
  • amyloid beta-protein (25-35)
  • Niacinamide
  • Niacin
  • Nitric Oxide
  • baicalein
  • Adenosine Triphosphate
  • Arginine
  • Proline
  • Electron Transport Complex I