The seed of Litchi chinensis fraction ameliorates hippocampal neuronal injury in an Aβ25-35-induced Alzheimer's disease rat model via the AKT/GSK-3β pathway

Pharm Biol. 2020 Dec;58(1):35-43. doi: 10.1080/13880209.2019.1697298.

Abstract

Context: The seed of Litchi chinensis Sonn., a famous traditional Chinese medicine, was recently reported to enhance cognitive function by inhibiting neuronal apoptosis in rats.Objective: We determined whether the seed of Litchi chinensis fraction (SLF) can ameliorate hippocampal neuronal injury via the AKT/GSK-3β pathway.Materials and methods: We established Alzheimer's disease (AD) model by infusing Aβ25-35 into the lateral ventricle of Sprague-Dawley (SD) rats and randomly divided into five groups (n = 10): sham, donepezil and SLF (120, 240 and 480 mg/kg/d). Rats were treated by intragastric administration for 28 consecutive days. Spatial learning and memory were evaluated with Morris water maze, while protein expression of AKT, GSK-3β and tau in the hippocampal neurons was measured by Western blotting and immunohistochemistry.Results: On the fifth day, escape latency of the AD model group was 45.78 ± 2.52 s and that of the sham operative group was 15.98 ± 2.32 s. SLF could improve cognitive functions by increasing the number of rats that crossed the platform (p < 0.01), and their platform quadrant dwell time (p < 0.05). The protein expression level of AKT was upregulated (p < 0.001), while that of GSK-3β and tau (p < 0.01) was remarkably downregulated in the hippocampal CA1 area.Discussion and conclusions: To our knowledge, the present study is the first to show that SLF may exert neuroprotective effect in AD rats via the AKT/GSK-3β signalling pathway, thereby serving as evidence for the potential utility of SLF as an effective drug against AD.

Keywords: AD; AKT; GSK-3β; Litchi chinensis seed fraction; beta-amyloid; botanical drug; cognitive function; neuroprotection; tau.

Publication types

  • Comparative Study

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Disease Models, Animal
  • Donepezil / pharmacology
  • Dose-Response Relationship, Drug
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Litchi / chemistry*
  • Male
  • Maze Learning / drug effects
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / isolation & purification
  • Neuroprotective Agents / pharmacology*
  • Peptide Fragments / toxicity
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Seeds

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Peptide Fragments
  • Plant Extracts
  • amyloid beta-protein (25-35)
  • Donepezil
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt

Grants and funding

This work was supported by Grants from the Science and Technology Planning Project of Sichuan Province of China under Grant numbers 2019YFSY0014, 2018JY0474, 2018JY0237 and 2019JDPT0010; Joint project of Luzhou Municipal People's Government and Southwest Medical University of China under Grant numbers 2018LZXNYD-ZK41, 2018LZXNYD-YL05 and 2019LZXNYDJ05; The National Natural Science Foundation of China under Grant numbers 81903829 and 81774013; Administration of Traditional Chinese Medicine of Sichuan Province of China under Grant numbers 2018QN070 and 2018JC013; Educational Commission of Sichuan Province of China under Grant numbers 18ZA0528 and 18TD0051; Health Commission of Sichuan Province of China under Grant number 18PJ019.