Microarray Expression Profile of Myricetin-Treated THP-1 Macrophages Exhibits Alterations in Atherosclerosis-Related Regulator Molecules and LXR/RXR Pathway
Atherosclerosis is a chronic inflammation characterized by macrophage infiltration, lipid deposition, and arterial wall thickening. Prevention of atherosclerosis by nutraceuticals is gaining attention. Myricetin, a dietary flavonol, is claimed to possess anti-atherosclerosis properties. We studied m...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/1/278 |
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| author | Etimad Huwait Rehab Almassabi Sanaa Almowallad Salma Saddeek Sajjad Karim Gauthaman Kalamegam Zeenat Mirza |
| author_facet | Etimad Huwait Rehab Almassabi Sanaa Almowallad Salma Saddeek Sajjad Karim Gauthaman Kalamegam Zeenat Mirza |
| author_sort | Etimad Huwait |
| collection | DOAJ |
| description | Atherosclerosis is a chronic inflammation characterized by macrophage infiltration, lipid deposition, and arterial wall thickening. Prevention of atherosclerosis by nutraceuticals is gaining attention. Myricetin, a dietary flavonol, is claimed to possess anti-atherosclerosis properties. We studied myricetin’s effect on the atherosclerosis-associated molecular mechanism. Cytotoxicity and proliferation testing to check the viability of myricetin-treated THP-1 macrophages and monocyte migration study in the presence and absence of myricetin was performed. The whole transcriptome analysis was conducted using the Affymetrix microarray platform. The Partek genomics suite for detecting differentially expressed genes (DEGs) and ingenuity pathway analysis was used to identify canonical pathways. Cytotoxicity assays exhibited no significant toxicity in THP-1 macrophages treated with different myricetin concentrations (10–200 μM). Genome-wide expression profiling revealed 58 DEGs (53 upregulated and 5 downregulated) in myricetin-treated THP-1 macrophages. Pathway analysis revealed inhibition of LXR/RXR activation and angiogenesis inhibition by thrombospondin-1 and activated phagocytosis in myricetin-treated THP-1 macrophages. The cytotoxicity assay shows myricetin as a safe phytochemical. In vitro and in silico pathway studies on THP-1 macrophages showed that they can inhibit THP-1 monocyte migration and alter the cholesterol efflux mediated via LXR/RXR signaling. Therefore, myricetin could help in the prevention of cell infiltration in atherosclerotic plaque with reduced risk of stroke or brain damage. |
| first_indexed | 2024-03-11T09:59:59Z |
| format | Article |
| id | doaj.art-9652fcdae6a24419aec6db1a7466503f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:59:59Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9652fcdae6a24419aec6db1a7466503f2023-11-16T15:31:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0124127810.3390/ijms24010278Microarray Expression Profile of Myricetin-Treated THP-1 Macrophages Exhibits Alterations in Atherosclerosis-Related Regulator Molecules and LXR/RXR PathwayEtimad Huwait0Rehab Almassabi1Sanaa Almowallad2Salma Saddeek3Sajjad Karim4Gauthaman Kalamegam5Zeenat Mirza6Biochemistry Department, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi ArabiaBiochemistry Department, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi ArabiaBiochemistry Department, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi ArabiaBiochemistry Department, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi ArabiaCenter for Transdisciplinary Research, Department of Pharmacology, Saveetha Institute of Medical and Technical Sciences, Saveetha Dental College and Hospital, Chennai 600077, IndiaDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi ArabiaAtherosclerosis is a chronic inflammation characterized by macrophage infiltration, lipid deposition, and arterial wall thickening. Prevention of atherosclerosis by nutraceuticals is gaining attention. Myricetin, a dietary flavonol, is claimed to possess anti-atherosclerosis properties. We studied myricetin’s effect on the atherosclerosis-associated molecular mechanism. Cytotoxicity and proliferation testing to check the viability of myricetin-treated THP-1 macrophages and monocyte migration study in the presence and absence of myricetin was performed. The whole transcriptome analysis was conducted using the Affymetrix microarray platform. The Partek genomics suite for detecting differentially expressed genes (DEGs) and ingenuity pathway analysis was used to identify canonical pathways. Cytotoxicity assays exhibited no significant toxicity in THP-1 macrophages treated with different myricetin concentrations (10–200 μM). Genome-wide expression profiling revealed 58 DEGs (53 upregulated and 5 downregulated) in myricetin-treated THP-1 macrophages. Pathway analysis revealed inhibition of LXR/RXR activation and angiogenesis inhibition by thrombospondin-1 and activated phagocytosis in myricetin-treated THP-1 macrophages. The cytotoxicity assay shows myricetin as a safe phytochemical. In vitro and in silico pathway studies on THP-1 macrophages showed that they can inhibit THP-1 monocyte migration and alter the cholesterol efflux mediated via LXR/RXR signaling. Therefore, myricetin could help in the prevention of cell infiltration in atherosclerotic plaque with reduced risk of stroke or brain damage.https://www.mdpi.com/1422-0067/24/1/278atherosclerosisgene expressionmicroarraymyricetinLXR/RXR signaling pathwayscavenger receptors |
| spellingShingle | Etimad Huwait Rehab Almassabi Sanaa Almowallad Salma Saddeek Sajjad Karim Gauthaman Kalamegam Zeenat Mirza Microarray Expression Profile of Myricetin-Treated THP-1 Macrophages Exhibits Alterations in Atherosclerosis-Related Regulator Molecules and LXR/RXR Pathway International Journal of Molecular Sciences atherosclerosis gene expression microarray myricetin LXR/RXR signaling pathway scavenger receptors |
| title | Microarray Expression Profile of Myricetin-Treated THP-1 Macrophages Exhibits Alterations in Atherosclerosis-Related Regulator Molecules and LXR/RXR Pathway |
| title_full | Microarray Expression Profile of Myricetin-Treated THP-1 Macrophages Exhibits Alterations in Atherosclerosis-Related Regulator Molecules and LXR/RXR Pathway |
| title_fullStr | Microarray Expression Profile of Myricetin-Treated THP-1 Macrophages Exhibits Alterations in Atherosclerosis-Related Regulator Molecules and LXR/RXR Pathway |
| title_full_unstemmed | Microarray Expression Profile of Myricetin-Treated THP-1 Macrophages Exhibits Alterations in Atherosclerosis-Related Regulator Molecules and LXR/RXR Pathway |
| title_short | Microarray Expression Profile of Myricetin-Treated THP-1 Macrophages Exhibits Alterations in Atherosclerosis-Related Regulator Molecules and LXR/RXR Pathway |
| title_sort | microarray expression profile of myricetin treated thp 1 macrophages exhibits alterations in atherosclerosis related regulator molecules and lxr rxr pathway |
| topic | atherosclerosis gene expression microarray myricetin LXR/RXR signaling pathway scavenger receptors |
| url | https://www.mdpi.com/1422-0067/24/1/278 |
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