Oleacein and Foam Cell Formation in Human Monocyte-Derived Macrophages: A Potential Strategy against Early and Advanced Atherosclerotic Lesions
Background: Oleacein is a secoiridoid group polyphenol found mostly in <i>Olea europea</i> L. and <i>Ligustrum vulgare</i> L. (Oleaceae). The aim of the present study was to investigate a potential role of oleacein in prevention of the foam cell formation. Materials and Metho...
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MDPI AG
2020-04-01
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| author | Agnieszka Filipek Tomasz P. Mikołajczyk Tomasz J. Guzik Marek Naruszewicz |
| author_facet | Agnieszka Filipek Tomasz P. Mikołajczyk Tomasz J. Guzik Marek Naruszewicz |
| author_sort | Agnieszka Filipek |
| collection | DOAJ |
| description | Background: Oleacein is a secoiridoid group polyphenol found mostly in <i>Olea europea</i> L. and <i>Ligustrum vulgare</i> L. (Oleaceae). The aim of the present study was to investigate a potential role of oleacein in prevention of the foam cell formation. Materials and Methods: Oleacein was isolated from <i>Ligustrum vulgare</i> leaves. Human monocyte-derived macrophages were obtained from monocytes cultured with Granulocyte-macrophage colony-stimulating factor (GM-CSF). Then, cells were incubated with 20 μM or 50 μM of oleacein and with oxidized low-density lipoprotein (oxLDL) (50 μg/mL). Visualization of lipid deposition within macrophages was carried out using Oil-Red-O. Expression of CD36, Scavenger receptor A1 (SRA1) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) was determined by Reverse transcription polymerase chain reaction (RT-PCR) and by flow cytometry. Apoptosis was determined by flow cytometry using Annexin V assay. STAT3 and Acyl-coenzyme A: cholesterol acyltransferase type 1 (ACAT1) levels were determined by ELISA. P-STAT3, P-JAK1, P-JAK2 expressions were determined by Western blot (WB). Results: Oleacein in dose-dependent manner significantly reduced lipid deposits in macrophages as well as their expression of selected scavenger receptors. The highest decrease of expression was found for CD36 and SRA1 receptors, from above 20% to more than 75% compared to oxLDL and the lowest for LOX-1 receptor, from approx. 8% to approx. 25% compared to oxLDL-stimulated macrophages. Oleacein significantly reduced (2.5-fold) early apoptosis of oxLDL-stimulated macrophages. Moreover, oleacein significantly increased the protein expression of JAK/STAT3 pathway and had no effect on ACAT1 level. Conclusions: Our study demonstrates, for the first time, that oleacein inhibits foam cell formation in human monocyte-derived macrophages and thus can be a valuable tool in the prevention of early and advanced atherosclerotic lesions. |
| first_indexed | 2024-03-10T20:33:40Z |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T20:33:40Z |
| publishDate | 2020-04-01 |
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| spelling | doaj.art-25f8666313f846bb98041d075e58f98a2023-11-19T21:08:55ZengMDPI AGPharmaceuticals1424-82472020-04-011346410.3390/ph13040064Oleacein and Foam Cell Formation in Human Monocyte-Derived Macrophages: A Potential Strategy against Early and Advanced Atherosclerotic LesionsAgnieszka Filipek0Tomasz P. Mikołajczyk1Tomasz J. Guzik2Marek Naruszewicz3Department of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, PolandInstitute of Infection, Immunity and Inflammation, University of Glasgow, Sir Graeme Davies Building 120 University Place, Glasgow G12 8TA, UKDepartment of Internal and Agricultural Medicine, Jagiellonian University Medical College, 31-007 Krakow, PolandDepartment of Pharmacognosy and Molecular Basis of Phytotherapy, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, PolandBackground: Oleacein is a secoiridoid group polyphenol found mostly in <i>Olea europea</i> L. and <i>Ligustrum vulgare</i> L. (Oleaceae). The aim of the present study was to investigate a potential role of oleacein in prevention of the foam cell formation. Materials and Methods: Oleacein was isolated from <i>Ligustrum vulgare</i> leaves. Human monocyte-derived macrophages were obtained from monocytes cultured with Granulocyte-macrophage colony-stimulating factor (GM-CSF). Then, cells were incubated with 20 μM or 50 μM of oleacein and with oxidized low-density lipoprotein (oxLDL) (50 μg/mL). Visualization of lipid deposition within macrophages was carried out using Oil-Red-O. Expression of CD36, Scavenger receptor A1 (SRA1) and Lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) was determined by Reverse transcription polymerase chain reaction (RT-PCR) and by flow cytometry. Apoptosis was determined by flow cytometry using Annexin V assay. STAT3 and Acyl-coenzyme A: cholesterol acyltransferase type 1 (ACAT1) levels were determined by ELISA. P-STAT3, P-JAK1, P-JAK2 expressions were determined by Western blot (WB). Results: Oleacein in dose-dependent manner significantly reduced lipid deposits in macrophages as well as their expression of selected scavenger receptors. The highest decrease of expression was found for CD36 and SRA1 receptors, from above 20% to more than 75% compared to oxLDL and the lowest for LOX-1 receptor, from approx. 8% to approx. 25% compared to oxLDL-stimulated macrophages. Oleacein significantly reduced (2.5-fold) early apoptosis of oxLDL-stimulated macrophages. Moreover, oleacein significantly increased the protein expression of JAK/STAT3 pathway and had no effect on ACAT1 level. Conclusions: Our study demonstrates, for the first time, that oleacein inhibits foam cell formation in human monocyte-derived macrophages and thus can be a valuable tool in the prevention of early and advanced atherosclerotic lesions.https://www.mdpi.com/1424-8247/13/4/64oleaceinhuman monocyte-derived macrophages (hMDMs)foam cell formationscavenger receptors (SR)JAK/STAT3 pathwayatherosclerosis |
| spellingShingle | Agnieszka Filipek Tomasz P. Mikołajczyk Tomasz J. Guzik Marek Naruszewicz Oleacein and Foam Cell Formation in Human Monocyte-Derived Macrophages: A Potential Strategy against Early and Advanced Atherosclerotic Lesions Pharmaceuticals oleacein human monocyte-derived macrophages (hMDMs) foam cell formation scavenger receptors (SR) JAK/STAT3 pathway atherosclerosis |
| title | Oleacein and Foam Cell Formation in Human Monocyte-Derived Macrophages: A Potential Strategy against Early and Advanced Atherosclerotic Lesions |
| title_full | Oleacein and Foam Cell Formation in Human Monocyte-Derived Macrophages: A Potential Strategy against Early and Advanced Atherosclerotic Lesions |
| title_fullStr | Oleacein and Foam Cell Formation in Human Monocyte-Derived Macrophages: A Potential Strategy against Early and Advanced Atherosclerotic Lesions |
| title_full_unstemmed | Oleacein and Foam Cell Formation in Human Monocyte-Derived Macrophages: A Potential Strategy against Early and Advanced Atherosclerotic Lesions |
| title_short | Oleacein and Foam Cell Formation in Human Monocyte-Derived Macrophages: A Potential Strategy against Early and Advanced Atherosclerotic Lesions |
| title_sort | oleacein and foam cell formation in human monocyte derived macrophages a potential strategy against early and advanced atherosclerotic lesions |
| topic | oleacein human monocyte-derived macrophages (hMDMs) foam cell formation scavenger receptors (SR) JAK/STAT3 pathway atherosclerosis |
| url | https://www.mdpi.com/1424-8247/13/4/64 |
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