Nelumbo nucifera leaves extract ameliorated scopolamine-induced cognition impairment via enhanced adult hippocampus neurogenesis

Environ Toxicol. 2024 May;39(5):3198-3210. doi: 10.1002/tox.24175. Epub 2024 Feb 14.

Abstract

In this presentation, we explored the molecular mechanisms of N. nucifera leaf water extracts (NLWEs) and polyphenol extract (NLPE) on scopolamine-induced cell apoptosis and cognition defects. The administration of NLWE and NLPE did not alter the body weight and serum biomarker rs and significantly ameliorated scopolamine-induced cognition impairment according to Y-maze test analysis. In mice, treatment with scopolamine disrupted normal histoarchitecture in the hippocampus, whereas the administration of NLWE and NLPE reversed the phenomenon. Western blot analysis revealed that scopolamine mitigated the expression of doublecortin (DCX), nestin, and NeuN, and cotreatment with NLWE or NLPE significantly recovered the expression of these proteins. NLWE and NLPE upregulated DCX and NeuN expression in the hippocampus region, as evidenced by immunohistochemical staining analysis of scopolamine-treated mice. NLWE and NLPE obviously elevated brain-derived neurotrophic factor (BDNF) and enhanced its downstream proteins activity. NLWE and NLPE attenuated scopolamine-induced apoptosis by reducing Bax and increased Bcl-2 expression. In addition, scopolamine also triggered apoptosis in human neuroblastoma SH-SY5Y cells whereas co-treatment with NLWE or quercetin-3-glucuronide (Q3G) reversed the phenomenon. NLWE or Q3G enhanced Bcl-2 and reduced Bax expression in the presence of scopolamine in SH-SY5Y cells. NLWE or Q3G recovered the inhibitory effects of scopolamine on neurogenesis and BDNF signals in SH-SY5Y cells. Overall, our results revealed that N. nucifera leaf extracts and Q3G promoted adult hippocampus neurogenesis and prevented apoptosis to mitigate scopolamine-induced cognition dysfunction through the regulation of BDNF signaling pathway.

Keywords: Nelumbo nucifera leaf extract; adult hippocampus neurogenesis; brain‐derived growth factor.

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cognition
  • Hippocampus / metabolism
  • Humans
  • Maze Learning
  • Mice
  • Nelumbo* / chemistry
  • Nelumbo* / metabolism
  • Neuroblastoma* / metabolism
  • Neurogenesis
  • Plant Extracts / chemistry
  • Scopolamine / metabolism
  • Scopolamine / pharmacology
  • bcl-2-Associated X Protein / metabolism

Substances

  • Scopolamine
  • Brain-Derived Neurotrophic Factor
  • bcl-2-Associated X Protein
  • Plant Extracts