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

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Neurodegenerative disorders involve progressive neuronal death driven by oxidative stress and neuroinflammation.
• Key therapeutic targets include the Nrf2 (antioxidant) and NF-κB (neuroinflammatory) pathways.
• Caffeic acid phenethyl ester (CAPE), found in propolis, exhibits neuroprotective effects by modulating Nrf2 and NF-κB.

Purpose of the Study:

• To review the biosynthesis, chemical synthesis, and diverse activities of CAPE derivatives.
• To summarize recent studies (2010-2023) on CAPE derivatives' neuroprotective potential.
• To highlight the role of CAPE derivatives in combating neuroinflammation and oxidative stress in neurological disorders.

Main Methods:

• Literature review of studies on CAPE derivatives from 2010 to 2023.
• Analysis of chemical synthesis strategies for CAPE derivatives.
• Evaluation of in vitro and in vivo studies demonstrating neuroprotective effects.

Main Results:

• CAPE derivatives, inspired by natural CAPE, show enhanced biological properties.
• These derivatives modulate both Nrf2 and NF-κB pathways, offering dual protection.
• Improved bioavailability and blood-brain barrier penetration of CAPE derivatives have been achieved through novel drug delivery systems.

Conclusions:

• CAPE derivatives represent a promising class of compounds for neuroprotection.
• Targeting Nrf2 and NF-κB pathways with CAPE derivatives offers a viable strategy for neurodegenerative and psychiatric disorders.
• Further research into CAPE derivatives and advanced delivery systems is warranted for clinical applications.