Byline: Ruth. Hornedo-Ortega, Ana. Espinosa-Oliva
Neuroinflammation in neurodegenerative diseases: Inflammatory processes play a critical role in neurodegenerative diseases, such as Parkinson's disease (PD). Thus, neuroinflammation is involved in the progression and development of these diseases, becoming an important pathological hallmark. Microglial cells, the 'macrophages' from central nervous system, are the initiating cells of the innate immune response against different stimuli in the brain. Even though they have a major role in brain homeostasis maintenance, their uncontrolled activation results in the secretion of pro-inflammatory cytokines and production of reactive oxygen species (ROS), leading to neuronal damage and death. Microglial cells present different phenotypes, ranging from pro-inflammatory/neurotoxic to anti-inflammatory/neuroprotective phenotype, depending on the stimulants involved (Shen et al., 2018). For this reason, novel therapeutic strategies are being addressed in order to shift the microglia polarization. Among them it is worth mentioning the search for dietary bioactive compounds, which may prevent or delay the progression of neuroinflammation and, in consequence, reduce the neuronal damage caused by microglia overactivation.
Mediterranean diet (MD) as a source of anti-inflammatory bioactive compounds. The case of hydroxytyrosol (HT): Supporting evidence has associated the adherence to MD with a significant decrease in the risk of developing PD. Actually, a recent systematic review based on 32 cohort studies concluded that MD has positive effects on cognitive health linking this effect to the high consumption of fruits, vegetables and virgin olive oil, characteristic of this diet pattern (Chen et al., 2019). All of these food sources are rich in polyphenolic compounds, a family of naturally occurring bioactive compounds (more than 8000) with proven overwhelming biological properties. Among them, it is worth mentioning 3,4-dihydroxyphenylethanol, also known as HT. HT, one of the major compounds present in the phenolic fraction of virgin olive oil (together with tyrosol and their secoiridoids derivatives), is considered nowadays a potent bioactive molecule for several reasons. Its concentration is high in virgin olive oil and olives, but significant quantities can be also found in beverages such as wine and beer. Moreover, HT is originated from the hydrolysis of olive oil secoiridoids, such as oleuropein. Indeed, after absorption of oleuropein in the gastrointestinal tract, its hydrolysis and metabolic transformation gives rise to HT. In addition, HT can be formed endogenously in humans from dopamine metabolism through the reduction of 3,4-dihydroxyphenylacetaldehyde to HT (Hashimoto et al., 2004). Thus, circulating HT not only depends on the dietary uptake but also on this endogenous formation. In this sense, higher HT plasma concentration should be expected in comparison with other polyphenols. Moreover, HT is able to cross the blood brain barrier (Serra et al., 2012), an important requirement if we want to use it as a neuroprotective agent.
First evidences of the potential role of HT as an anti-inflammatory agent in brain: Very recently, in vivo and in vitro studies carried out by us and other authors have firstly demonstrated that HT could be used as anti-inflammatory agent to combat diseases such as PD, modulating microglial response (Gallardo-Fernández et al., 2019; Zhang et...