Ligustrazine Attenuates Hyperhomocysteinemia-induced Alzheimer-like Pathologies in Rats

Curr Med Sci. 2021 Jun;41(3):548-554. doi: 10.1007/s11596-021-2379-1. Epub 2021 Jun 25.

Abstract

Ligustrazine, an alkaloid extracted from the traditional Chinese herbal medicine Ligusticum Chuanxiong Hort, has been clinically applied to treat the cerebrovascular diseases. Hyperhomocysteinemia (Hhcy) is an independent risk factor for Alzheimer's disease (AD). Memory deficits can be caused by Hhcy via pathologies of AD-like tau and amyloid-β (Aβ) in the hippocampus. Here, we investigated whether homocysteine (Hcy) can induce AD-like pathologies and the effects of ligustrazine on these pathologies. The Hcy rat model was constructed by 14-day Hcy injection via vena caudalis, and rats were treated with daily intragastric administration of ligustrazine at the same time. We found that the pathologies of tau and Aβ were induced by Hcy in the hippocampus, while the Hcy-induced tau hyperphosphorylation and Aβ accumulation could be markedly attenuated by simultaneous ligustrazine treatment. Our data demonstrate that ligustrazine may be used as a promising neuroprotective agent to treat the Hcy-induced AD-like pathologies.

Keywords: Alzheimer’s disease; cognitive impairment; hyperhomocysteinemia; ligustrazine; phosphorylated tau.

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / etiology
  • Alzheimer Disease / genetics
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides
  • Animals
  • Brain / drug effects
  • Brain / pathology
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Humans
  • Hyperhomocysteinemia / complications
  • Hyperhomocysteinemia / drug therapy*
  • Hyperhomocysteinemia / genetics
  • Hyperhomocysteinemia / pathology
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology
  • Memory Disorders / genetics
  • Memory Disorders / pathology
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Phosphorylation / drug effects
  • Pyrazines / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Pyrazines
  • tetramethylpyrazine