Treatment with the Olive Secoiridoid Oleacein Protects against the Intestinal Alterations Associated with EAE
Multiple sclerosis (MS) is a CNS inflammatory demyelinating disease. Recent investigations highlight the gut-brain axis as a communication network with crucial implications in neurological diseases. Thus, disrupted intestinal integrity allows the translocation of luminal molecules into systemic circ...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/5/4977 |
| _version_ | 1797615094748676096 |
|---|---|
| author | Beatriz Gutiérrez-Miranda Isabel Gallardo Eleni Melliou Isabel Cabero Yolanda Álvarez Marta Hernández Prokopios Magiatis Marita Hernández María Luisa Nieto |
| author_facet | Beatriz Gutiérrez-Miranda Isabel Gallardo Eleni Melliou Isabel Cabero Yolanda Álvarez Marta Hernández Prokopios Magiatis Marita Hernández María Luisa Nieto |
| author_sort | Beatriz Gutiérrez-Miranda |
| collection | DOAJ |
| description | Multiple sclerosis (MS) is a CNS inflammatory demyelinating disease. Recent investigations highlight the gut-brain axis as a communication network with crucial implications in neurological diseases. Thus, disrupted intestinal integrity allows the translocation of luminal molecules into systemic circulation, promoting systemic/brain immune-inflammatory responses. In both, MS and its preclinical model, the experimental autoimmune encephalomyelitis (EAE) gastrointestinal symptoms including “leaky gut” have been reported. Oleacein (OLE), a phenolic compound from extra virgin olive oil or olive leaves, harbors a wide range of therapeutic properties. Previously, we showed OLE effectiveness preventing motor defects and inflammatory damage of CNS tissues on EAE mice. The current studies examine its potential protective effects on intestinal barrier dysfunction using MOG<sub>35-55</sub>-induced EAE in C57BL/6 mice. OLE decreased EAE-induced inflammation and oxidative stress in the intestine, preventing tissue injury and permeability alterations. OLE protected from EAE-induced superoxide anion and accumulation of protein and lipid oxidation products in colon, also enhancing its antioxidant capacity. These effects were accompanied by reduced colonic IL-1β and TNFα levels in OLE-treated EAE mice, whereas the immunoregulatory cytokines IL-25 and IL-33 remained unchanged. Moreover, OLE protected the mucin-containing goblet cells in colon and the serum levels of iFABP and sCD14, markers that reflect loss of intestinal epithelial barrier integrity and low-grade systemic inflammation, were significantly reduced. These effects on intestinal permeability did not draw significant differences on the abundance and diversity of gut microbiota. However, OLE induced an EAE-independent raise in the abundance of <i>Akkermansiaceae</i> family. Consistently, using Caco-2 cells as an in vitro model, we confirmed that OLE protected against intestinal barrier dysfunction induced by harmful mediators present in both EAE and MS. This study proves that the protective effect of OLE in EAE also involves normalizing the gut alterations associated to the disease. |
| first_indexed | 2024-03-11T07:21:38Z |
| format | Article |
| id | doaj.art-81bbc17dc73b41a9a9691bb0ccc11006 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T07:21:38Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-81bbc17dc73b41a9a9691bb0ccc110062023-11-17T07:56:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01245497710.3390/ijms24054977Treatment with the Olive Secoiridoid Oleacein Protects against the Intestinal Alterations Associated with EAEBeatriz Gutiérrez-Miranda0Isabel Gallardo1Eleni Melliou2Isabel Cabero3Yolanda Álvarez4Marta Hernández5Prokopios Magiatis6Marita Hernández7María Luisa Nieto8Instituto de Biomedicina y Genética Molecular de Valladolid (IBGM-CSIC/UVa), 47003 Valladolid, SpainInstituto de Biomedicina y Genética Molecular de Valladolid (IBGM-CSIC/UVa), 47003 Valladolid, SpainLaboratory of Pharmacognosy and Natural Products Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, GreeceInstituto de Biomedicina y Genética Molecular de Valladolid (IBGM-CSIC/UVa), 47003 Valladolid, SpainInstituto de Biomedicina y Genética Molecular de Valladolid (IBGM-CSIC/UVa), 47003 Valladolid, SpainLaboratorio de Biología Molecular y Microbiología, Instituto Tecnológico Agrario de Castilla y León (ITACyL), 47071 Valladolid, SpainLaboratory of Pharmacognosy and Natural Products Chemistry, Department of Pharmacy, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, GreeceInstituto de Biomedicina y Genética Molecular de Valladolid (IBGM-CSIC/UVa), 47003 Valladolid, SpainInstituto de Biomedicina y Genética Molecular de Valladolid (IBGM-CSIC/UVa), 47003 Valladolid, SpainMultiple sclerosis (MS) is a CNS inflammatory demyelinating disease. Recent investigations highlight the gut-brain axis as a communication network with crucial implications in neurological diseases. Thus, disrupted intestinal integrity allows the translocation of luminal molecules into systemic circulation, promoting systemic/brain immune-inflammatory responses. In both, MS and its preclinical model, the experimental autoimmune encephalomyelitis (EAE) gastrointestinal symptoms including “leaky gut” have been reported. Oleacein (OLE), a phenolic compound from extra virgin olive oil or olive leaves, harbors a wide range of therapeutic properties. Previously, we showed OLE effectiveness preventing motor defects and inflammatory damage of CNS tissues on EAE mice. The current studies examine its potential protective effects on intestinal barrier dysfunction using MOG<sub>35-55</sub>-induced EAE in C57BL/6 mice. OLE decreased EAE-induced inflammation and oxidative stress in the intestine, preventing tissue injury and permeability alterations. OLE protected from EAE-induced superoxide anion and accumulation of protein and lipid oxidation products in colon, also enhancing its antioxidant capacity. These effects were accompanied by reduced colonic IL-1β and TNFα levels in OLE-treated EAE mice, whereas the immunoregulatory cytokines IL-25 and IL-33 remained unchanged. Moreover, OLE protected the mucin-containing goblet cells in colon and the serum levels of iFABP and sCD14, markers that reflect loss of intestinal epithelial barrier integrity and low-grade systemic inflammation, were significantly reduced. These effects on intestinal permeability did not draw significant differences on the abundance and diversity of gut microbiota. However, OLE induced an EAE-independent raise in the abundance of <i>Akkermansiaceae</i> family. Consistently, using Caco-2 cells as an in vitro model, we confirmed that OLE protected against intestinal barrier dysfunction induced by harmful mediators present in both EAE and MS. This study proves that the protective effect of OLE in EAE also involves normalizing the gut alterations associated to the disease.https://www.mdpi.com/1422-0067/24/5/4977multiple sclerosisEAEoleaceinintestinal permeabilityinflammation |
| spellingShingle | Beatriz Gutiérrez-Miranda Isabel Gallardo Eleni Melliou Isabel Cabero Yolanda Álvarez Marta Hernández Prokopios Magiatis Marita Hernández María Luisa Nieto Treatment with the Olive Secoiridoid Oleacein Protects against the Intestinal Alterations Associated with EAE International Journal of Molecular Sciences multiple sclerosis EAE oleacein intestinal permeability inflammation |
| title | Treatment with the Olive Secoiridoid Oleacein Protects against the Intestinal Alterations Associated with EAE |
| title_full | Treatment with the Olive Secoiridoid Oleacein Protects against the Intestinal Alterations Associated with EAE |
| title_fullStr | Treatment with the Olive Secoiridoid Oleacein Protects against the Intestinal Alterations Associated with EAE |
| title_full_unstemmed | Treatment with the Olive Secoiridoid Oleacein Protects against the Intestinal Alterations Associated with EAE |
| title_short | Treatment with the Olive Secoiridoid Oleacein Protects against the Intestinal Alterations Associated with EAE |
| title_sort | treatment with the olive secoiridoid oleacein protects against the intestinal alterations associated with eae |
| topic | multiple sclerosis EAE oleacein intestinal permeability inflammation |
| url | https://www.mdpi.com/1422-0067/24/5/4977 |
| work_keys_str_mv | AT beatrizgutierrezmiranda treatmentwiththeolivesecoiridoidoleaceinprotectsagainsttheintestinalalterationsassociatedwitheae AT isabelgallardo treatmentwiththeolivesecoiridoidoleaceinprotectsagainsttheintestinalalterationsassociatedwitheae AT elenimelliou treatmentwiththeolivesecoiridoidoleaceinprotectsagainsttheintestinalalterationsassociatedwitheae AT isabelcabero treatmentwiththeolivesecoiridoidoleaceinprotectsagainsttheintestinalalterationsassociatedwitheae AT yolandaalvarez treatmentwiththeolivesecoiridoidoleaceinprotectsagainsttheintestinalalterationsassociatedwitheae AT martahernandez treatmentwiththeolivesecoiridoidoleaceinprotectsagainsttheintestinalalterationsassociatedwitheae AT prokopiosmagiatis treatmentwiththeolivesecoiridoidoleaceinprotectsagainsttheintestinalalterationsassociatedwitheae AT maritahernandez treatmentwiththeolivesecoiridoidoleaceinprotectsagainsttheintestinalalterationsassociatedwitheae AT marialuisanieto treatmentwiththeolivesecoiridoidoleaceinprotectsagainsttheintestinalalterationsassociatedwitheae |