(−)-Methyl-Oleocanthal, a New Oleocanthal Metabolite Reduces LPS-Induced Inflammatory and Oxidative Response: Molecular Signaling Pathways and Histones Epigenetic Modulation
The antioxidant and anti-inflammatory responses of (−)-methyl-oleocanthal (met-OLE), a new metabolite of the extra virgin olive oil (EVOO) phenolic oleocanthal (OLE), were explored in lipopolysaccharide (LPS)-induced murine peritoneal macrophages. Possible signaling pathways and epigenetic modulatio...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/1/56 |
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| author | Tatiana Montoya Catalina Alarcón-de-la-Lastra María Luisa Castejón Juan Ortega-Vidal Joaquín Altarejos Marina Sánchez-Hidalgo |
| author_facet | Tatiana Montoya Catalina Alarcón-de-la-Lastra María Luisa Castejón Juan Ortega-Vidal Joaquín Altarejos Marina Sánchez-Hidalgo |
| author_sort | Tatiana Montoya |
| collection | DOAJ |
| description | The antioxidant and anti-inflammatory responses of (−)-methyl-oleocanthal (met-OLE), a new metabolite of the extra virgin olive oil (EVOO) phenolic oleocanthal (OLE), were explored in lipopolysaccharide (LPS)-induced murine peritoneal macrophages. Possible signaling pathways and epigenetic modulation of histones were studied. Met-OLE inhibited LPS-induced intracellular reactive oxygen species (ROS) and nitrite (NO) production and decreased the overexpression of the pro-inflammatory enzymes COX-2, mPGES-1 and iNOS in murine macrophages. In addition, met-OLE was able to significantly decrease the activation of p38, JNK, and ERK mitogen-activated protein kinases (MAPKs) and blocked canonical and non-canonical inflammasome signaling pathways. On the contrary, met-OLE upregulated haem oxigenase 1 (HO-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) expression in treated cells. Finally, met-OLE pretreated spleen cells counteracted LPS induction, preventing H3K18 acetylation or H3K9 and H3K27 demethylation. Overall, these results provide novel mechanistic insights into the beneficial effects of met-OLE regarding the regulation of the immune–inflammatory response through epigenetic changes in histone markers. This revealing evidence suggests that the methylated metabolite of OLE may contribute significantly to the beneficial effects that are associated with the secoiridoid-related compound and the usual consumption of EVOO. |
| first_indexed | 2024-03-10T03:01:19Z |
| format | Article |
| id | doaj.art-f7dafd3493e247e59181d1ed02fe8a87 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T03:01:19Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-f7dafd3493e247e59181d1ed02fe8a872023-11-23T12:46:36ZengMDPI AGAntioxidants2076-39212021-12-011115610.3390/antiox11010056(−)-Methyl-Oleocanthal, a New Oleocanthal Metabolite Reduces LPS-Induced Inflammatory and Oxidative Response: Molecular Signaling Pathways and Histones Epigenetic ModulationTatiana Montoya0Catalina Alarcón-de-la-Lastra1María Luisa Castejón2Juan Ortega-Vidal3Joaquín Altarejos4Marina Sánchez-Hidalgo5Department of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, SpainDepartment of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, SpainDepartment of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, SpainDepartment of Inorganic and Organic Chemistry, Faculty of Experimental Sciences, Campus de Excelencia Internacional Agroalimentario (ceiA3), University of Jaén, 23071 Jaén, SpainDepartment of Inorganic and Organic Chemistry, Faculty of Experimental Sciences, Campus de Excelencia Internacional Agroalimentario (ceiA3), University of Jaén, 23071 Jaén, SpainDepartment of Pharmacology, Faculty of Pharmacy, Universidad de Sevilla, 41012 Sevilla, SpainThe antioxidant and anti-inflammatory responses of (−)-methyl-oleocanthal (met-OLE), a new metabolite of the extra virgin olive oil (EVOO) phenolic oleocanthal (OLE), were explored in lipopolysaccharide (LPS)-induced murine peritoneal macrophages. Possible signaling pathways and epigenetic modulation of histones were studied. Met-OLE inhibited LPS-induced intracellular reactive oxygen species (ROS) and nitrite (NO) production and decreased the overexpression of the pro-inflammatory enzymes COX-2, mPGES-1 and iNOS in murine macrophages. In addition, met-OLE was able to significantly decrease the activation of p38, JNK, and ERK mitogen-activated protein kinases (MAPKs) and blocked canonical and non-canonical inflammasome signaling pathways. On the contrary, met-OLE upregulated haem oxigenase 1 (HO-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf-2) expression in treated cells. Finally, met-OLE pretreated spleen cells counteracted LPS induction, preventing H3K18 acetylation or H3K9 and H3K27 demethylation. Overall, these results provide novel mechanistic insights into the beneficial effects of met-OLE regarding the regulation of the immune–inflammatory response through epigenetic changes in histone markers. This revealing evidence suggests that the methylated metabolite of OLE may contribute significantly to the beneficial effects that are associated with the secoiridoid-related compound and the usual consumption of EVOO.https://www.mdpi.com/2076-3921/11/1/56antioxidanthistonesinflammationmacrophagesmetabolitemethylation |
| spellingShingle | Tatiana Montoya Catalina Alarcón-de-la-Lastra María Luisa Castejón Juan Ortega-Vidal Joaquín Altarejos Marina Sánchez-Hidalgo (−)-Methyl-Oleocanthal, a New Oleocanthal Metabolite Reduces LPS-Induced Inflammatory and Oxidative Response: Molecular Signaling Pathways and Histones Epigenetic Modulation Antioxidants antioxidant histones inflammation macrophages metabolite methylation |
| title | (−)-Methyl-Oleocanthal, a New Oleocanthal Metabolite Reduces LPS-Induced Inflammatory and Oxidative Response: Molecular Signaling Pathways and Histones Epigenetic Modulation |
| title_full | (−)-Methyl-Oleocanthal, a New Oleocanthal Metabolite Reduces LPS-Induced Inflammatory and Oxidative Response: Molecular Signaling Pathways and Histones Epigenetic Modulation |
| title_fullStr | (−)-Methyl-Oleocanthal, a New Oleocanthal Metabolite Reduces LPS-Induced Inflammatory and Oxidative Response: Molecular Signaling Pathways and Histones Epigenetic Modulation |
| title_full_unstemmed | (−)-Methyl-Oleocanthal, a New Oleocanthal Metabolite Reduces LPS-Induced Inflammatory and Oxidative Response: Molecular Signaling Pathways and Histones Epigenetic Modulation |
| title_short | (−)-Methyl-Oleocanthal, a New Oleocanthal Metabolite Reduces LPS-Induced Inflammatory and Oxidative Response: Molecular Signaling Pathways and Histones Epigenetic Modulation |
| title_sort | methyl oleocanthal a new oleocanthal metabolite reduces lps induced inflammatory and oxidative response molecular signaling pathways and histones epigenetic modulation |
| topic | antioxidant histones inflammation macrophages metabolite methylation |
| url | https://www.mdpi.com/2076-3921/11/1/56 |
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