Hydroxytyrosol and Cytoprotection: A Projection for Clinical Interventions

Abstract

Hydroxytyrosol (HT) ((3,4-Dihydroxyphenyl)ethanol) is a polyphenol mainly present in extra virgin olive oil (EVOO) but also in red wine. It has a potent antioxidant effect related to hydrogen donation, and the ability to improve radical stability. The phenolic content of olive oil varies between 100 and 600 mg/kg, due to multiple factors (place of cultivation, climate, variety of the olive and level of ripening at the time of harvest), with HT and its derivatives providing half of that content. When consumed, EVOO’s phenolic compounds are hydrolyzed in the stomach and intestine, increasing levels of free HT which is then absorbed in the small intestine, forming phase II metabolites. It has been demonstrated that HT consumption is safe even at high doses, and that is not genotoxic or mutagenic in vitro. The beneficial effects of HT have been studied in humans, as well as cellular and animal models, mostly in relation to consumption of EVOO. Many properties, besides its antioxidant capacity, have been attributed to this polyphenol. The aim of this review was to assess the main properties of HT for human health with emphasis on those related to the possible prevention and/or treatment of non-communicable diseases.

Docosahexaenoic acid and hydroxytyrosol co‐administration fully prevents liver steatosis and related parameters in mice subjected to high‐fat diet: A molecular approach

“…Data presented using mice fed a HFD for 12 weeks show significant decreases ( p < .05) in NF‐κB up‐regulation and NF‐κB‐dependent target expression of pro‐inflammatory genes by HT (Figure ). Considering that ROS activate NF‐κB, which in turn triggers the expression of inflammasome NLRP3 components, cytokines, chemokines and adhesion molecules, inhibition of NF‐κB signaling by HT, in association with its potent antioxidant capacity, supports the anti‐inflammatory effects of HT. Together, data reported indicate that DHA and HT co‐administration suppresses HFD‐induced liver pro‐inflammatory state by down‐regulation of NF‐κB signaling (Figure ), which is associated with the enhancement the antioxidant capacity of the liver over control values (Figure ) and supported by the significant inverse correlation established between NF‐κB DNA binding and that of Nrf2 ( r = −.90; p < .001).…”

“…The latter finding is associated with decreased liver FFA influx and increased FAO that may contribute to diminish hepatic TG and VLDL synthesis . Second, the protective effects of HT in liver injury models are primarily related to its polyphenolic structure, which confers its free‐radical scavenging and metal chelating properties, therefore lowering free‐radical levels and oxidative stress status (Figure ), with the concomitant increase the antioxidant potential of the liver (Figure 5). Consequently, HT may favor FAO over de novo lipogenesis through maintenance of the basal level of n‐ 3 LCPUFAs that supports PPAR‐α (Figure ) over SREBP‐1c (Figure ) functioning.…”

“…66 The antiinflammatory effect exerted by DHA is characterized by being more effective than that of arachidonic acid (C20:4n-6; AA) 65 and opposite to that of palmitic acid. 64 In addition to DHA, HT is known to exert beneficial effects related to the metabolic syndrome and its complications by diminishing oxidative stress and inflammation, as demonstrated in different biological models using several inflammation inducers, 52,53 including rats subjected to HFD for 5 weeks. 67 Data presented using mice fed a HFD for 12 weeks show significant decreases (p < .05) in NF-κB up-regulation and NF-κB-dependent target expression of pro-inflammatory genes by HT ( Figure 6).…”

“…Hepatic NF-κB DNA binding (a) and NF-κB mRNA levels (b), and tumor necrosis factor α (TNF-α) mRNA levels in liver (c) and in serum (d), interleukin 6 (IL-6) mRNA levels in liver (e) and in serum (f) and IL-1β mRNA levels in liver (g) and in serum (h). For group definition, data expression and significance design see legend to Figure 1 expression of inflammasome NLRP3 components, cytokines, chemokines and adhesion molecules, 68 inhibition of NF-κB signaling by HT, in association with its potent antioxidant capacity, 52,53 supports the anti-inflammatory effects of HT. Together, data reported indicate that DHA and HT co-administration suppresses HFD-induced liver pro-inflammatory state by down-regulation of NF-κB signaling ( Figure 6), which is associated with the enhancement the antioxidant capacity of the liver over control values ( Figure 5) and supported by the significant inverse correlation established between NF-κB DNA binding and that of Nrf2 (r = −.90; p < .001).…”

Hydroxytyrosol prevents dermal papilla cells inflammation under oxidative stress by inducing autophagy

“…Clinical research have already shown that the Mediterranean diet may reduce the risk of alopecia thereby reducing the percentage of telogen and the proportion of miniaturized anagen hair . Hydroxytyrosol (HT), as a powerful antioxidant and major phenol in olive oil, presents a variety of pharmacological effects, such as antioxidant, anti‐inflammatory, and improvement of autophagy in both the pharmaceutical and cosmetic applications . It has also been shown the HT antiapoptotic effect against UVB stress in a human keratinocytes model confirming its beneficial properties and a possible application in the sun skin protection .…”