Unsaturated Fatty Alcohol Derivatives of Olive Oil Phenolic Compounds with Potential Low-Density Lipoprotein (LDL) Antioxidant and Antiobesity Properties

Abstract

A new route for the synthesis of fatty alcohol derivatives of hydroxytyrosol and other olive oil phenolic compounds was developed to allow the preparation of unsaturated derivatives. The biological activity of synthesized compounds was evaluated. Most of the compounds presented a significant antioxidant activity on low-density lipoprotein (LDL) particles. The activity of the tested products was significantly influenced by the number and position of unsaturations as well as modifications on the polar head of the synthesized compounds. Some of them presented modulation of food intake in rats and, due to their molecular similarity with CB(1) endogenous ligands, the endocannabinoid system and PPAR-α were also evaluated as potential targets. The pharmacodynamics could not be totally explained by CB(1) and PPAR-α receptor interactions because only two of the four compounds with biological activity showed a CB(1) activity and all of them presented low PPAR-α affinity, not justifying its whole in vivo activity. The hydroxytyrosol linoleylether (7) increased LDL resistance to oxidation with a capacity similar to that of hydroxytyrosol and was the most active in vivo compound with a hypophagic effect comparable to that of oleoylethanolamine. We consider that this compound could be a good lead compound for future drug development in obesity treatments.

Sensibility of male rats fertility against olive oil, Nigella sativa oil and pomegranate extract

“…Recently, it has been reported that OO phenols are strong antioxidants that have biological activities which may account for the observed beneficial influences of the Mediterranean diet [26] .…”

“…Virgin OO contains many phenolic compounds including oleuropein and hydroxytyrosol which are thought to be the principal components conferring the characteristic taste and stability of OO [26] . The results of the present study could be explained by what was observed by Kano et al [27] , who reported that dietary supplementation with oleuropein could alter the hormonal level of those associated with protein anabolism by increasing urinary noradrenaline and testicular testosterone hormone levels and decreasing plasma corticosterone level in rats.…”

Health effects of olive oil polyphenols: Recent advances and possibilities for the use of health claims

“…Drira reported that both hydroxytyrosol (100 and 150 μM) and oleuropein (200 and 300 μM) inhibited adipocyte differentiation by inhibiting the mitotic clonal expansion and by downregulating adipogenesis‐related genes . In animal models, some unsaturated fatty alcohol derivatives of hydroxytyrosol, particularly hydroxytyrosol linoleylether (5 mg/kg), showed a hypophagic effect comparable to that of oleoylethanolamine, despite a lower affinity for the cannabinoid CB1 receptor and the PPAR‐α receptor .…”

Obesity as a Condition Determined by Food Addiction: Should Brain Endocannabinoid System Alterations Be the Cause and Its Modulation the Solution?

“…The same molecule was effective in reducing voluntary ethanol intake in mice, suggesting it may be a good candidate to treat food addiction [192]. Other drugs act on both PPARα and CB1 receptors to exert their anti-obesogenic activity, as is the case for Compound7 [193] and OLHHA [194]. For certain, the most numerous classes are made up of drugs acting both on CB1 and CB2 receptors.…”