| Title: |
Unraveling the Protective Role of Oleocanthal and Its Oxidation Product, Oleocanthalic Acid, against Neuroinflammation |
| Authors: |
Barbalace MC; Freschi M; Rinaldi I; Zallocco L; Malaguti M; Manera C; Ortore G; Zuccarini M; Ronci M; Cuffaro D; Macchia M; Hrelia S; Giusti L; Digiacomo M; Angeloni C |
| Contributors: |
Barbalace MC, Freschi M, Rinaldi I, Zallocco L, Malaguti M, Manera C, Ortore G, Zuccarini M, Ronci M, Cuffaro D, Macchia M, Hrelia S, Giusti L, Digiacomo M, Angeloni C |
| Publication Year: |
2024 |
| Collection: |
IRIS Università degli Studi di Bologna (CRIS - Current Research Information System) |
| Subject Terms: |
oleocanthal; oleocanthalic acid; neuroinflammation; BV-2 microglial cell; lipopolysaccharide; TLR4; ACOD1; gelsolin; 14-3-3 protein family; clathrin |
| Description: |
Neuroinflammation is a critical aspect of various neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. This study investigates the anti-neuroinflammatory properties of oleocanthal and its oxidation product, oleocanthalic acid, using the BV-2 cell line activated with lipopolysaccharide. Our findings revealed that oleocanthal significantly inhibited the production of pro-inflammatory cytokines and reduced the expression of inflammatory genes, counteracted oxidative stress induced by lipopolysaccharide, and increased cell phagocytic activity. Conversely, oleocanthalic acid was not able to counteract lipopolysaccharide-induced activation. The docking analysis revealed a plausible interaction of oleocanthal, with both CD14 and MD-2 leading to a potential interference with TLR4 signaling. Since our data show that oleocanthal only partially reduces the lipopolysaccharide-induced activation of NF-kB, its action as a TLR4 antagonist alone cannot explain its remarkable effect against neuroinflammation. Proteomic analysis revealed that oleocanthal counteracts the LPS modulation of 31 proteins, including significant targets such as gelsolin, clathrin, ACOD1, and four different isoforms of 14-3-3 protein, indicating new potential molecular targets of the compound. In conclusion, oleocanthal, but not oleocanthalic acid, mitigates neuroinflammation through multiple mechanisms, highlighting a pleiotropic action that is particularly important in the context of neurodegeneration. |
| Document Type: |
article in journal/newspaper |
| File Description: |
ELETTRONICO |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/39334733; info:eu-repo/semantics/altIdentifier/wos/WOS:001323719100001; volume:13; issue:9; firstpage:1; lastpage:31; numberofpages:31; journal:ANTIOXIDANTS; https://hdl.handle.net/11585/990877 |
| DOI: |
10.3390/antiox13091074 |
| Availability: |
https://hdl.handle.net/11585/990877; https://doi.org/10.3390/antiox13091074; https://www.mdpi.com/2076-3921/13/9/1074 |
| Rights: |
info:eu-repo/semantics/openAccess ; license:Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY) ; license uri:iris.PUB15 |
| Accession Number: |
edsbas.482ECDC9 |
| Database: |
BASE |