The Neuroprotective Potential of Seed Extract from the Indian Trumpet Tree Against Amyloid Beta-Induced Toxicity in SH-SY5Y Cells

Int J Mol Sci. 2025 Jun 29;26(13):6288. doi: 10.3390/ijms26136288.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with an unclear etiology. Multiple factors, including oxidative stress and the accumulation of amyloid beta (Aβ) protein in the brain, contribute to neuronal damage. This study investigated Aβ-induced oxidative stress and cellular damage in SH-SY5Y cells, as well as the neuroprotective potential of Indian trumpet tree seed extract (ITS). SH-SY5Y cells were co-treated with Aβ(25-35) (20 µM) and ITS extract at concentrations of 25 and 50 µg/mL. Cell viability, reactive oxygen species (ROS), malondialdehyde (MDA) levels, and the enzymatic activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were assessed. The expression levels of B-cell lymphoma 2 (Bcl-2) and caspase-3, along with the phosphorylation levels of protein kinase B (Akt), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and cAMP response element-binding protein (CREB), were also evaluated. ITS extract at concentrations of 25 and 50 µg/mL significantly improved SH-SY5Y cell viability following Aβ-induced damage; reduced ROS and MDA levels; and enhanced CAT, SOD, and GSH-Px activities. In addition to upregulating Bcl-2 expression, ITS downregulated caspase-3 expression and increased the phosphorylation of Akt, ERK1/2, and CREB. High-performance liquid chromatography (HPLC) analysis identified baicalin, baicalein, and chrysin as major phenolic compounds in ITS extract. In conclusion, ITS extract attenuated Aβ-induced oxidative stress, enhanced antioxidant defenses and cell viability, suppressed apoptotic signaling, and activated key neuroprotective pathways. These findings provide new insights into the neuroprotective potential of ITS extract; however, further in vivo studies are needed to validate its clinical applicability.

Keywords: Alzheimer’s disease; Indian trumpet tree; Oroxylum indicum (L.) seed; cAMP response element-binding protein; mitogen-activated protein kinases; neuroprotection; oxidative stress; plant extraction; protein kinase B.

MeSH terms

  • Amyloid beta-Peptides* / toxicity
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • Malondialdehyde / metabolism
  • Neuroprotective Agents* / chemistry
  • Neuroprotective Agents* / pharmacology
  • Oxidative Stress / drug effects
  • Plant Extracts* / chemistry
  • Plant Extracts* / pharmacology
  • Reactive Oxygen Species / metabolism
  • Seeds* / chemistry
  • Superoxide Dismutase / metabolism
  • Terminalia* / chemistry

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Plant Extracts
  • Reactive Oxygen Species
  • Malondialdehyde
  • Superoxide Dismutase
  • Antioxidants