Nutritionally relevant concentrations of resveratrol and hydroxytyrosol mitigate oxidative burst of human granulocytes and monocytes and the production of pro-inflammatory mediators in LPS-stimulated RAW 264.7 macrophages

Bigagli, Elisabetta; Cinci, Lorenzo; Paccosi, Sara; Parenti, Astrid; D’Ambrosio, Mario; Luceri, Cristina

doi:10.1016/j.intimp.2016.12.012

Cited by 97 publications

(75 citation statements)

References 56 publications

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“…They showed that only RSV and hydroxytyrosol (at 10 µM) decreased miR-146a, which is known to target Nrf2 responsible for inhibiting pro-inflammatory mediators. In addition, the authors showed that Nrf2 was increased by RSV and hydroxytyrosol after in vitro stimulation of murine macrophages with LPS [148]. Lançon et al reported that of 26 miRNAs were increased (miR-21 and miR-27b) in prevalence by RSV in mouse C2C12 skeletal myoblasts, while other 20 miRNAs (miR-20b and miR-133, a muscle-specific miRNA known to target genes involved in myoblast differentiation) were downregulated [149,150].…”

Section: Stilbenesmentioning

confidence: 98%

“…These data suggest the potential modulation of miR-663 levels to stimulate the anti-inflammatory effects of RSV in metabolic disorders associated with elevated levels of miR-155. Since many in vitro experiments use high concentrations of phenolic compounds and do not reproduce their physiological in vivo plasma levels, Bigagli et al incubated RAW264.7 macrophages with corresponding plasma physiological concentrations of RSV, hydroxytyrosol and oleuropein [148]. They showed that only RSV and hydroxytyrosol (at 10 µM) decreased miR-146a, which is known to target Nrf2 responsible for inhibiting pro-inflammatory mediators.…”

Section: Stilbenesmentioning

confidence: 99%

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Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

et al. 2020

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Atherosclerosis is the main process behind cardiovascular diseases (CVD), maladies which continue to be responsible for up to 70% of death worldwide. Despite the ongoing development of new and potent drugs, their incomplete efficacy, partial intolerance and numerous side effects make the search for new alternatives worthwhile. The focus of the scientific world turned to the potential of natural active compounds to prevent and treat CVD. Essential for effective prevention or treatment based on phytochemicals is to know their mechanisms of action according to their bioavailability and dosage. The present review is focused on the latest data about phenolic compounds and aims to collect and correlate the reliable existing knowledge concerning their molecular mechanisms of action to counteract important risk factors that contribute to the initiation and development of atherosclerosis: dyslipidemia, and oxidative and inflammatory-stress. The selection of phenolic compounds was made to prove their multiple benefic effects and endorse them as CVD remedies, complementary to allopathic drugs. The review also highlights some aspects that still need clear scientific explanations and draws up some new molecular approaches to validate phenolic compounds for CVD complementary therapy in the near future.In the last decade the scientific researchers turned their attention to phytochemicals, as effective, safe and low-cost natural bioactive compounds for CVD treatment.Dyslipidemia consists of increased blood concentrations of total cholesterol (TC), low density lipoproteins-cholesterol (LDL-C) and/or triglycerides (TG), and decreased high density lipoproteins-cholesterol (HDL-C) [6]. The lipid metabolism is complex and the candidate mechanisms that could generate dyslipidemia include: (i) excessive dietary lipid absorption in the small intestine; (ii) packing of exogenous lipids with cholesterol and fatty acids produced de novo in the liver and their secretion as very low density lipoproteins (VLDL); (iii) hydrolysis of TG from VLDL by lipases and their conversion into LDL, which are taken up by the peripheral tissues through LDL receptor (LDL-R) and scavenger receptors; (iv) diminished production of HDL by the liver and small intestine, thereby decreasing reverse cholesterol transport (RCT) from the peripheral tissues to the liver; (v) lowered excess cholesterol excretion from the liver into gallbladder or to the intestinal lumen through the ATP-binding cassette G5 and G8 transporters (ABCG5/G8) that facilitate trans-intestinal cholesterol efflux (TICE). Dyslipidemia is associated with the accumulation of LDL in the sub-endothelium of the artery wall. At this site, LDL undergoes oxidative modifications (oxLDL) that trigger inflammatory responses, and is taken up by the monocyte-derived macrophages infiltrated in the sub-endothelium which thus become lipid-loaded foam cells, the hallmark of atheroma development [7]. Until now, the most effective lipid-lowering treatment for hyperlipidemic patients was the statin therapy. But recen...

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Section: Stilbenesmentioning

confidence: 98%

Section: Stilbenesmentioning

confidence: 99%

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

et al. 2020

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“…The anti-inflammatory activity of HT has been previously tested on macrophage cell lines, with the TLR-4 ligand lipopolysaccharide (LPS) as a stimulating agent, and proved that HT diminished the secretion of cytokines induced by LPS, including IL-1α, IL-1β, IL-6, IL-12, and TNF-α, as well as chemokines, such as C-X-C motif chemokine 10 (CXCL10/IP-10) and monocyte chemoattractant protein 1 (MCP-1/CCL2), through a mechanism non-dependent on the NF-κB signaling pathway [17][18][19]. Another recent study has proved that HT in LPS-treated RAW264.7 cells modulates oxidative stress by the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2) [20]. However, to our knowledge, the effect of HT has never been tested in microglia, the leading actors driving the brain immune response under disease conditions.…”

Section: Introductionmentioning

confidence: 99%

Hydroxytyrosol Decreases LPS- and α-Synuclein-Induced Microglial Activation In Vitro

et al. 2019

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I.M.A.-B.); rodriguez@us.es (J.A.R.-G.); jlvenero@us.es (J.L.V.); depablos@us.es (R.M.d.P.)Abstract: Neuroinflammation is a common feature shared by neurodegenerative disorders, such as Parkinson's disease (PD), and seems to play a key role in their development and progression. Microglia cells, the principal orchestrators of neuroinflammation, can be polarized in different phenotypes, which means they are able to have anti-inflammatory, pro-inflammatory, or neurodegenerative effects. Increasing evidence supports that the traditional Mediterranean dietary pattern is related to the reduction of cognitive decline in neurodegenerative diseases. A considerable intake of plant foods, fish, and extra virgin olive oil (EVOO), as well as a moderate consumption of red wine, all characteristic of the Mediterranean diet (MD), are behind these effects. These foods are especially rich in polyphenols, being the most relevant in the MD hydroxytyrosol (HT) and their derivatives present in EVOO, which have demonstrated a wide array of biological activities. Here, we demonstrate that HT is able to reduce the inflammation induced by two different stimuli: lipopolysaccharide and α-synuclein. We also study the possible molecular mechanisms involved in the anti-inflammatory effect of HT, including the study of nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and inflammasome. Our data support the use of HT to prevent the inflammation associated with PD and shed light into the relationship between MD and this neurological disorder.

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“…Oleuropein is also a radical scavenger and a LDL oxidation blocker [7]. We have recently reported that the anti-inflammatory effects of hydroxytyrosol were detected at pharmacologically relevant concentrations and involved decreased nitric oxide (NO) and PGE2 production and NRF2 and miR-146a modulation [8]. Recent studies have also indicated that the beneficial effects of the phenolic compounds from extra-virgin olive oil (EVOO) may be related to their impact on the genome, since they modify the expression of genes involved in many cellular processes and in particular oxidative stress, inflammation, DNA repair, and metabolism pathways [3, 9].…”

Section: Introductionmentioning

confidence: 99%

Dietary Extra-Virgin Olive Oil Polyphenols Do Not Attenuate Colon Inflammation in Transgenic HLAB-27 Rats but Exert Hypocholesterolemic Effects through the Modulation of HMGCR and PPAR-α Gene Expression in the Liver

Bigagli¹,

Toti²,

Lodovici³

et al. 2018

Lifestyle Genomics

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Background: Human studies have demonstrated that olive oil phenolic compounds reduce inflammatory markers associated with chronic diseases. Objectives: To explore the anti-inflammatory effects of extra-virgin olive oil polyphenols in an experimental model of inflammatory bowel disease (IBD). Methods: HLA-B27 transgenic rats were fed an AIN-76 diet containing 10% corn oil (CO) or extra-virgin olive oil with high (EVOO) or low phenolic content (ROO) for 3 months. Wild-type rats (WT) were fed the CO diet. Results: CO-fed HLA-B27 animals developed intestinal inflammation characterized by diarrhea, increased myeloperoxidase activity, and mucosal injury. None of these parameters were influenced by EVOO. Gene expression profiling indicated that proinflammatory pathways were upregulated in the colon mucosa of CO-fed HLA-B27 rats compared to WT, and this was further confirmed by RT-PCR for the iNOS, TNFα, and IL1β genes. EVOO significantly reduced TNFα gene expression in the colon mucosa and decreased total cholesterol blood levels compared to CO HLA-B27 rats (89.43 ± 3.66 vs. 111.5 ± 8.10 mg/dL, p < 0.05). This latter effect with EVOO was associated with reduced HMGCR and increased PPAR-α hepatic gene expression, compared to ROO. Conclusion: These data indicate that olive oil polyphenols do not control colon inflammation in HLA-B27 transgenic rats but exert a positive effect on blood lipids by reducing total cholesterol levels. This preliminary result suggests the need to explore the efficacy of EVOO rich in polyphenols as a complementary strategy for managing hypercholesterolemia and to potentially limit statin-associated myotoxicity.

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Nutritionally relevant concentrations of resveratrol and hydroxytyrosol mitigate oxidative burst of human granulocytes and monocytes and the production of pro-inflammatory mediators in LPS-stimulated RAW 264.7 macrophages

Cited by 97 publications

References 56 publications

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

Phenolic Compounds Exerting Lipid-Regulatory, Anti-Inflammatory and Epigenetic Effects as Complementary Treatments in Cardiovascular Diseases

Hydroxytyrosol Decreases LPS- and α-Synuclein-Induced Microglial Activation In Vitro

Dietary Extra-Virgin Olive Oil Polyphenols Do Not Attenuate Colon Inflammation in Transgenic HLAB-27 Rats but Exert Hypocholesterolemic Effects through the Modulation of HMGCR and PPAR-α Gene Expression in the Liver

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