Caffeic Acid Phenethyl Ester (CAPE): Biosynthesis, Derivatives and Formulations with Neuroprotective Activities

Rebeca Pérez*, Viviana Burgos*, Víctor Marín*, Antoni Camins*, Jordi Olloquequi*, Iván González-Chavarría*, Henning Ulrich*, Ursula Wyneke*, Alejandro Luarte*, Leandro Ortiz*, Cristian Paz*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations


Neurodegenerative disorders are characterized by a progressive process of degeneration and neuronal death, where oxidative stress and neuroinflammation are key factors that contribute to the progression of these diseases. Therefore, two major pathways involved in these pathologies have been proposed as relevant therapeutic targets: The nuclear transcription factor erythroid 2 (Nrf2), which responds to oxidative stress with cytoprotecting activity; and the nuclear factor NF-κB pathway, which is highly related to the neuroinflammatory process by promoting cytokine expression. Caffeic acid phenethyl ester (CAPE) is a phenylpropanoid naturally found in propolis that shows important biological activities, including neuroprotective activity by modulating the Nrf2 and NF-κB pathways, promoting antioxidant enzyme expression and inhibition of proinflammatory cytokine expression. Its simple chemical structure has inspired the synthesis of many derivatives, with aliphatic and/or aromatic moieties, some of which have improved the biological properties. Moreover, new drug delivery systems increase the bioavailability of these compounds in vivo, allowing its transcytosis through the blood-brain barrier, thus protecting brain cells from the increased inflammatory status associated to neurodegenerative and psychiatric disorders. This review summarizes the biosynthesis and chemical synthesis of CAPE derivatives, their miscellaneous activities, and relevant studies (from 2010 to 2023), addressing their neuroprotective activity in vitro and in vivo.

Original languageEnglish
Article number1500
Pages (from-to)1-20
Number of pages20
Issue number8
StatePublished - Aug 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.


  • anti-inflammatory
  • antioxidant
  • caffeic acid phenethyl ester
  • CAPE derivatives
  • neuroprotection
  • NF-κB
  • Nrf2


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