FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Protects against Oxidative Stress-Mediated Neuronal Cell Apoptosis and Scopolamine-Induced Cognitive Impairment by Activating Nrf2/HO-1 Signaling

Ting Wan, Zihao Wang, Yi Luo, Yifan Zhang, Wei He, Yu Mei, Jincheng Xue, Min Li, Huafeng Pan, Weirong Li, Qi Wang*, Yujie Huang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)

Abstract

Alzheimer's disease (AD) is an age-related neurodegenerative disorder with cognitive deficits, which is becoming markedly more common in the world. Currently, the exact cause of AD is still unclear, and no curative therapy is available for preventing or mitigating the disease progression. Caffeic acid phenethyl ester (CAPE), a natural phenolic compound derived from honeybee hive propolis, has been reported as a potential therapeutic agent against AD, while its application is limited due to the low water solubility and poor bioavailability. Here, caffeic acid phenethyl ester 4-O-glucoside (FA-97) is synthesized. We validate that FA-97 attenuates H2O2-induced apoptosis in SH-SY5Y and PC12 cells and suppresses H2O2-induced oxidative stress by inhibiting the ROS level, malondialdehyde (MDA) level, and protein carbonylation level, as well as induces cellular glutathione (GSH) and superoxide dismutase (SOD). Mechanistically, FA-97 promotes the nuclear translocation and transcriptional activity of Nrf2 associated with the upregulated expression of HO-1 and NQO-1. The prime importance of Nrf2 activation in the neuroprotective and antioxidant effects of FA-97 is verified by Nrf2 siRNA transfection. In addition, FA-97 prevents scopolamine- (SCOP-) induced learning and memory impairments in vivo via reducing neuronal apoptosis and protecting against cholinergic system dysfunction in the hippocampus and cortex. Moreover, the increased MDA level and low total antioxidant capacity in SCOP-treated mouse brains are reversed by FA-97, with the increased expression of HO-1, NQO-1, and nuclear Nrf2. In conclusion, FA-97 protects against oxidative stress-mediated neuronal cell apoptosis and SCOP-induced cognitive impairment by activating Nrf2/HO-1 signaling, which might be developed as a therapeutic drug for AD.

Original languageEnglish
Article number8239642
JournalOxidative Medicine and Cellular Longevity
Volume2019
DOIs
Publication statusPublished - 3 Dec 2019

Scopus Subject Areas

  • Biochemistry
  • Ageing
  • Cell Biology

Fingerprint

Dive into the research topics of 'FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Protects against Oxidative Stress-Mediated Neuronal Cell Apoptosis and Scopolamine-Induced Cognitive Impairment by Activating Nrf2/HO-1 Signaling'. Together they form a unique fingerprint.

Cite this