Bacopa monnieri confers neuroprotection by influencing signaling pathways associated with interleukin 4, 13 and extracellular matrix organization in Alzheimer's disease: A proteomics-based perspective

Neurochem Int. 2024 Nov:180:105864. doi: 10.1016/j.neuint.2024.105864. Epub 2024 Sep 29.

Abstract

Alzheimer's disease, a prevalent neurodegenerative disorder in the elderly, is characterized by the accumulation of senile plaques and neurofibrillary tangles, triggering oxidative stress, neuroinflammation, and neuronal apoptosis. Current therapies focus on symptomatic treatment rather than targeting the underlying disease-modifying molecular mechanisms and are often associated with significant side effects. Bacopa monnieri, a traditional Indian herb with nootropic properties, has shown promise in neurological disorder treatment from ancient times. However, its mechanisms of action in Alzheimer's disease remain elusive. In this study, a cellular model for Alzheimer's disease was created by treating differentiated IMR-32 cells with beta-amyloid, 1-42 peptide (Aβ42). Additionally, a recovery model was established through co-treatment with Bacopa monnieri to explore its protective mechanism. Co-treatment with Bacopa monnieri extract recovered Aβ42 induced damage as evidenced by the decreased apoptosis and reduced reactive oxygen species production. Mass spectrometry-based quantitative proteomic analysis identified 21,674 peptides, corresponding to 3626 proteins from the Alzheimer's disease model. The proteins dysregulated by Aβ42 were implicated in cellular functions, such as negative regulation of cell proliferation and microtubule cytoskeleton organization. The enriched pathways include extracellular matrix organization and interleukin-4 and interleukin-13 signaling. Bacopa monnieri co-treatment showed remarkable restoration of Aβ42 altered proteins, including FOSL1, and TDO2. The protein-protein interaction network analysis of Bacopa monnieri restored proteins identified the hub gene involved in Alzheimer's disease. The findings from this study may open up new avenues for creating innovative therapeutic approaches for Alzheimer's disease.

Keywords: Alzheimer's disease; Neurodegenerative disease; Neurodegenerative diseases; Proteomics; Traditional medicine.

MeSH terms

  • Alzheimer Disease* / drug therapy
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides* / metabolism
  • Bacopa* / chemistry
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Humans
  • Interleukin-4 / metabolism
  • Interleukin-4 / pharmacology
  • Neuroprotection / drug effects
  • Neuroprotection / physiology
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Peptide Fragments / metabolism
  • Peptide Fragments / toxicity
  • Plant Extracts* / pharmacology
  • Plant Extracts* / therapeutic use
  • Proteomics* / methods
  • Signal Transduction* / drug effects

Substances

  • Plant Extracts
  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Interleukin-4
  • Peptide Fragments
  • amyloid beta-protein (1-42)