Phenolic Compounds Characteristic of the Mediterranean Diet in Mitigating Microglia-Mediated Neuroinflammation

Abstract

Neuroinflammation is a pathological feature of quite a number of Central Nervous System diseases such as Alzheimer and Parkinson’s disease among others. The hallmark of brain neuroinflammation is the activation of microglia, which are the immune resident cells in the brain and represents the first line of defense when injury or disease occur. Microglial activated cells can adopt different phenotypes to carry out its diverse functions. Thus, the shift into pro-inflammatory/neurotoxic or anti-inflammatory/neuroprotective phenotypes, depending of the brain environment, has totally changed the understanding of microglia in neurodegenerative disease. For this reason, novel therapeutic strategies which aim to modify the microglia polarization are being developed. Additionally, the understanding of how nutrition may influence the prevention and/or treatment of neurodegenerative diseases has grown greatly in recent years. The protective role of Mediterranean diet (MD) in preventing neurodegenerative diseases has been reported in a number of studies. The Mediterranean dietary pattern includes as distinctive features the moderate intake of red wine and extra virgin olive oil, both of them rich in polyphenolic compounds, such as resveratrol, oleuropein and hydroxytyrosol and their derivatives, which have demonstrated anti-inflammatory effects on microglia on in vitro studies. This review summarizes our understanding of the role of dietary phenolic compounds characteristic of the MD in mitigating microglia-mediated neuroinflammation, including explanation regarding their bioavailability, metabolism and blood–brain barrier.

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

“…Previous studies have shown the antioxidant and anti-inflammatory properties of HT in several models of human diseases, such as rheumatoid arthritis, hepatic and intestinal inflammation, diabetes, glioma, and osteoarthritis, among others [34]. In vitro studies have also revealed the anti-inflammatory effects of HT in monocytes/macrophages and point out some of its possible mechanism of action [17][18][19]. However, the possible anti-inflammatory properties of HT in microglia, the main immune cells in the CNS, have remained unexplored.…”

“…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].…”

Hydroxytyrosol stimulates neurogenesis in aged dentate gyrus by enhancing stem and progenitor cell proliferation and neuron survival

“…[23][24][25][26] In fact, HTyr reduces oxidative stress in brain slices undergoing such stress, that is, lipid peroxidation, peroxynitrite formation, and production of inflammatory mediators (prostaglandin E2 and interleukin 1beta) 27 ; similarly, HTyr protects in vitro from oxidative stress, by rescuing either PC12 cells or SH-SY5Y neuroblastoma cells from 6-hydroxydopamine-induced damage, from L-DOPA toxicity or preventing hydrogen peroxide-induced death. [28][29][30] Moreover, HTyr is able to cross the blood-brain barrier 31,32 and its treatment in a mouse model of Alzheimer's disease (TgCRND8 mice) caused a significant reduction of the amyloid-β plaque number in hippocampal areas. 33 However, despite the extensive literature about the modulation of adult neurogenesis by several phenolic compounds (34,35, for review), little is known about the potential role of HTyr in this process in vivo.…”

Natural Compounds and Autophagy: Allies Against Neurodegeneration

“…Chronic neurodegenerative diseases are untreatable and few approved synthetic drugs reduced adverse symptoms but not cure them. In this discouraging scenario, oral supplementation with vegetal bioactive derivatives or the Mediterranean diet are promising to postpone the irreversible progression of AD, PD, ALS, FTD (Vauzour et al, 2017;Hornedo-Ortega et al, 2018;Pohl and Lin, 2018;Fernandez-Sanz et al, 2019).…”