Grapefruit Flavonoid Naringenin Regulates the Expression of LXRα in THP-1 Macrophages by Modulating AMP-Activated Protein Kinase

Sáenz, Javier; Santa-María, Consuelo; Reyes-Quiróz, María Edith; Geniz, Isabel; Jiménez, Juan; Sobrino, Francisco; Álba, Gonzalo

doi:10.1021/acs.molpharmaceut.7b00797

Cited by 25 publications

(24 citation statements)

References 56 publications

(117 reference statements)

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“…The flavonoids naringenin, 339 quercetin, 358 and vitexin 359 increased ABCA1 / Abca1 mRNA 339 , 359 and ABCA1 protein levels 339 , 360 , 358 by induction of LXRA/ Lxra mRNA 358 , 359 and LXR-α protein. 339 , 360 The effect of naringenin and the standard ABCA1 / Abca1 inducer TO901317 were additive. Naringenin was shown to be dependent on the cAMP-activated protein kinase (AMPK) regulation ( AMPK ), as well as SREBP1C regulation.…”

Section: Part I: Status Quomentioning

confidence: 97%

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

Pahnke

Bascuñana

Brackhan

et al. 2021

Free Neuropathology

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Adenosine-triphosphate-(ATP)-binding cassette (ABC) transport proteins are ubiquitously present membrane-bound efflux pumps that distribute endo- and xenobiotics across intra- and intercellular barriers. Discovered over 40 years ago, ABC transporters have been identified as key players in various human diseases, such as multidrug-resistant cancer and atherosclerosis, but also neurodegenerative diseases, such as Alzheimer’s disease (AD). Most prominent and well-studied are ABCB1, ABCC1, and ABCG2, not only due to their contribution to the multidrug resistance (MDR) phenotype in cancer, but also due to their contribution to AD. However, our understanding of other ABC transporters is limited, and most of the 49 human ABC transporters have been largely neglected as potential targets for novel small-molecule drugs. This is especially true for the ABCA subfamily, which contains several members known to play a role in AD initiation and progression. This review provides up-to-date information on the proposed functional background and pathological role of ABCA transporters in AD. We also provide an overview of small-molecules shown to interact with ABCA transporters as well as potential in silico , in vitro , and in vivo methodologies to gain novel templates for the development of innovative ABC transporter-targeting diagnostics and therapeutics.

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Section: Part I: Status Quomentioning

confidence: 97%

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

Pahnke

Bascuñana

Brackhan

et al. 2021

Free Neuropathology

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“…Naringenin upregulated LXRα at mRNA and protein levels and its target genes in an AMPK dependent manner in THP1 macrophages (Kemmerer, Wittig, Richter, Brüne, & Namgaladze, 2016;Saenz et al, 2017).…”

Section: Naringeninmentioning

confidence: 98%

“…Naringenin is found in oranges and grapefruits and is one of the major citrus flavanones (Saenz et al, 2017). Preclinical studies showed that naringenin increased the levels of HDL and LPL in Wistar rats, which were fed with ethanol alone, and can efficiently prevent the accumulation of plasma lipids and lipoproteins (Jayachitra & Nalini, 2012).…”

Section: Naringeninmentioning

confidence: 99%

Effects of phytochemicals on macrophage cholesterol efflux capacity: Impact on atherosclerosis

Soltani

Boozari

Cicero

et al. 2021

Phytotherapy Research

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High‐density lipoprotein cholesterol (HDL) is the major promoter of reverse cholesterol transport and efflux of excess cellular cholesterol. The functions of HDL, such as cholesterol efflux, are associated with cardiovascular disease rather than HDL levels. We have reviewed the evidence base on the major classes of phytochemicals, including polyphenols, alkaloids, carotenoids, phytosterols, and fatty acids, and their effects on macrophage cholesterol efflux and its major pathways. Phytochemicals show the potential to improve the efficiency of each of these pathways. The findings are mainly in preclinical studies, and more clinical research is warranted in this area to develop novel clinical applications.

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“…Real-time RT-PCR was performed with a Quanti-Fast SYBR Green PCR kit, using a StepOnePlus Real-time PCR machine (Applied Biosystems, Foster City, CA, United States). Primers for the following target genes ICAM-1 and MCP-1 were obtained from a previously published report : ABCA-1 (Moss, 2018), CD36, SR-A (Xu et al, 2006), and LXR-α (Saenz et al, 2018), and the housekeeping gene glyceraldehyde-3phosphate dehydrogenase (GAPDH) was obtained from the work of . Primer details are listed in Table 1.…”

Section: Real-time Quantitative Reverse Transcription-polymerase Chain Reactionmentioning

confidence: 99%

Antiatherogenic Effects of Quercetin in the THP-1 Macrophage Model In Vitro, With Insights Into Its Signaling Mechanisms Using In Silico Analysis

et al. 2021

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Background: Atherosclerosis (AS), a major risk factor for stroke and brain tissue destruction, is an inflammatory disease of the blood vessels, and the underlying pathology is inflammation mediated by various chemokines and cytokines. Quercetin, a natural flavonol, is reported to have both anti-inflammatory and antioxidant properties. As such, in the present study, we evaluated the antiatherogenic effects of quercetin in a human THP-1 cell line in vitro and also the signaling mechanisms using in silico analysis.Materials and Methods: THP-1 macrophages exposed to different concentrations of quercetin (5–100 μM for 24 h) were tested for cytotoxicity. Real-time gene expression assay for intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) was carried out following treatment with quercetin at 15 and 30 μM for 24 h either in the absence or presence of interferon (IFN-γ) for 3 h to induce inflammation. Monocyte migration and cholesterol efflux were also assessed.Results: Quercetin did not exert any cytotoxic effects on THP-1 cells at the various concentrations tested. The gene expression assay showed a significant decrease in ICAM-1 (by 3.05 and 2.70) and MCP-1 (by 22.71 and 27.03), respectively. Quercetin at 15 µM decreased THP-1 monocyte migration by 33% compared to the MCP-1-treated cells. It also increased cholesterol efflux significantly by1.64-fold and 1.60-fold either alone or in combination with IFN-γ, respectively. Ingenuity Pathway Analysis of the molecular interactions of quercetin identified canonical pathways directly related to lipid uptake and cholesterol efflux. Furthermore, CD36, SR-A, and LXR-α also demonstrated significant increases by 72.16-, 149.10-, and 29.68-fold, respectively.Conclusion: Our results from both in vitro and in silico studies identified that quercetin inhibited the THP-1 monocyte migration, MCP-1, and ICAM-1 and increased cholesterol efflux probably mediated via the LXR/RXR signaling pathway. Therefore, quercetin will help prevent cell infiltration in atherosclerotic plaques and reduce the risk of stroke or brain destruction.

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Grapefruit Flavonoid Naringenin Regulates the Expression of LXRα in THP-1 Macrophages by Modulating AMP-Activated Protein Kinase

Cited by 25 publications

References 56 publications

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

Effects of phytochemicals on macrophage cholesterol efflux capacity: Impact on atherosclerosis

Antiatherogenic Effects of Quercetin in the THP-1 Macrophage Model In Vitro, With Insights Into Its Signaling Mechanisms Using In Silico Analysis

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