Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Therapeutic Potential of Caffeic Acid Phenethyl Ester (Cape) and Derivatives With Anti-inflammatory, Antioxidant, and Neuroprotective Activities

Rebeca Perez
,
Viviana Burgos
,
Víctor Marín
,
Antonio Camins
ORCID logo ,
Jordi Olloquequi.
,
Ivan Gonzalez-Chavarría
,
Henning Ulrich
ORCID logo ,
Ursula Wyneken
,
Leandro Ortiz
,
Cristian Paz
* ORCID logo
Version 1 : Received: 30 May 2023 / Approved: 31 May 2023 / Online: 31 May 2023 (05:32:19 CEST)

A peer-reviewed article of this Preprint also exists.

Pérez, R.; Burgos, V.; Marín, V.; Camins, A.; Olloquequi, J.; González-Chavarría, I.; Ulrich, H.; Wyneke, U.; Luarte, A.; Ortiz, L.; Paz, C. Caffeic Acid Phenethyl Ester (CAPE): Biosynthesis, Derivatives and Formulations with Neuroprotective Activities. Antioxidants 2023, 12, 1500. Pérez, R.; Burgos, V.; Marín, V.; Camins, A.; Olloquequi, J.; González-Chavarría, I.; Ulrich, H.; Wyneke, U.; Luarte, A.; Ortiz, L.; Paz, C. Caffeic Acid Phenethyl Ester (CAPE): Biosynthesis, Derivatives and Formulations with Neuroprotective Activities. Antioxidants 2023, 12, 1500.

Abstract

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-kB 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.

Keywords

caffeic acid phenethyl ester; CAPE derivatives; anti-inflammatory; NF-kB; antioxidant; Nrf2; neuroprotection

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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