Sarcococca saligna ameliorated D-galactose induced neurodegeneration through repression of neurodegenerative and oxidative stress biomarkers

Metab Brain Dis. 2023 Feb;38(2):717-734. doi: 10.1007/s11011-022-01046-w. Epub 2022 Jul 26.

Abstract

Sarcococca saligna is a valuable source of bioactive secondary metabolites exhibiting antioxidant, anti-inflammatory and acetylcholinesterase inhibitory activities. The study was intended to explore the therapeutic pursuits of S. saligna in amelioration of cognitive and motor dysfunctions induced by D-galactose and linked mechanistic pathways. Alzheimer's disease model was prepared by administration of D-galactose subcutaneous injection100 mg/kg and it was treated with rivastigmine (100 mg/kg, orally) and plant extract for 42 days. Cognitive and motor functions were evaluated by behavioral tasks and oxidative stress biomarkers. Level of acetylcholinesterase, reduced level of glutathione, protein and nitrite level, and brain neurotransmitters were analyzed in brain homogenate. The level of apoptosis regulator Bcl-2, Caspases 3 and heat shock protein HSP-70 in brain homogenates were analyzed by ELISA and colorimetric method, respectively. AChE, IL-1β, TNF-α, IL-1α and β secretase expressions were analyzed by RT-PCR. S. saligna dose dependently suppressed the neurodegenerative effects of D-galactose induced behavioral and biochemical impairments through modulation of antioxidant enzymes and acetylcholinesterase inhibition. S. saligna markedly (P < 0.05) ameliorated the level of brain neurotransmitters, Bcl-2, HSP-70 and Caspases-3 level. S. saligna at 500-1000 mg/kg considerably recovered the mRNA expression of neurodegenerative and neuro-inflammatory biomarkers, also evident from histopathological analysis. These findings suggest that S. saligna could be applicable in cure of Alzheimer's disease.

Keywords: Acetylcholinesterase; Alzheimer’s disease; Cognitive and motor functions; Neurodegeneration; Sarcococca saligna.

MeSH terms

  • Acetylcholinesterase / metabolism
  • Alzheimer Disease* / metabolism
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Biomarkers / metabolism
  • Buxaceae*
  • Caspases / metabolism
  • Galactose / pharmacology
  • Maze Learning
  • Oxidative Stress
  • Proto-Oncogene Proteins c-bcl-2 / metabolism

Substances

  • Antioxidants
  • Acetylcholinesterase
  • Galactose
  • Proto-Oncogene Proteins c-bcl-2
  • Biomarkers
  • Caspases