Protective effect of caffeic acid against alzheimer's disease pathogenesis via modulating cerebral insulin signaling, β-Amyloid Accumulation, and Synaptic Plasticity in Hyperinsulinemic Rats

Wenchang Chang, Dawei Huang, Y. Martin Lo, Qinqiao Tee, Poling Kuo, James Swibea Wu, Wenchung Huang, Szuchuan Shen

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This study investigated the alleviative effect of caffeic acid (CA) on Alzheimer's disease (AD) pathogenesis and associated mechanisms in high-fat (HF) diet-induced hyperinsulinemic rats. The results of a Morris water maze indicated that, by administrating CA (30 mg/kg b.w./day) for 30 weeks, the memory and learning impairments in HF-induced hyperinsulinemic rats were significantly ameliorated. CA also enhanced superoxide dismutase and glutathione free radical scavenger activity in hyperinsulinemic rats. The Western blot data further confirmed that protein expressions of phosphorylated-glycogen synthase kinase 3β (GSK3β) were significantly increased, whereas the expression of phosphorylated-tau protein decreased in the hippocampus of rats administered with CA in comparison with the HF group. Moreover, the expression of amyloid precursor protein (APP) and β-site APP cleaving enzyme were attenuated, subsequently lowering the level of β-amyloid 1-42 (Aβ 1-42) in the hippocampus of CA-treated hyperinsulinemic rats. CA also significantly increased the expression of synaptic proteins in HF rats.

Original languageEnglish
Pages (from-to)7684-7693
Number of pages10
JournalJournal of Agricultural and Food Chemistry
Issue number27
Publication statusPublished - 2019 Jul 10



  • Alzheimer's disease
  • caffeic acid
  • cerebral carbohydrate metabolism
  • hyperinsulinemic

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

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