期刊
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
卷 4, 期 1, 页码 179-192出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsptsci.0c00166
关键词
oleocanthal; pharmacokinetics; biological fluids; glycine derivative; oleoglycine; tyrosol acetate
资金
- National Institute of Neurological Disorders and Stroke (NIH/NINDS) [R21NS101506]
- Louisiana Board of Regents [LEQSF (2017-20-RD-B-07)]
- World Olive Center for Health
This study demonstrates the spontaneous reaction of (-)-oleocanthal with amino acids, with a high preferential reactivity to glycine, resulting in the formation of two products: oleoglycine, an unusual glycine derivative with a tetrahydropyridinium skeleton, and tyrosol acetate. Extensive research was conducted to validate the reactivity of oleocanthal, followed by pharmacokinetic studies in mice and cell culture transport studies to assess the ability of the formed derivatives to cross physiological barriers like the blood-brain barrier. This novel finding provides a new perspective on the bioactivities of oleocanthal in humans.
Since the first discovery of its ibuprofen-like anti-inflammatory activity in 2005, the olive phenolic (-)-oleocanthal gained great scientific interest and popularity due to its reported health benefits. (-)-Oleocanthal is a monophenolic secoiridoid exclusively occurring in extra-virgin olive oil (EVOO). While several groups have investigated oleocanthal pharmacokinetics (PK) and disposition, none was able to detect oleocanthal in biological fluids or identify its PK profile that is essential for translational research studies. Besides, oleocanthal could not be detected following its addition to any fluid containing amino acids or proteins such as plasma or culture media, which could be attributed to its unique structure with two highly reactive aldehyde groups. Here, we demonstrate that oleocanthal spontaneously reacts with amino acids, with high preferential reactivity to glycine compared to other amino acids or proteins, affording two products: an unusual glycine derivative with a tetrahydropyridinium skeleton that is named oleoglycine, and our collective data supported the plausible formation of tyrosol acetate as the second product. Extensive studies were performed to validate and confirm oleocanthal reactivity, which were followed by PK disposition studies in mice, as well as cell culture transport studies to determine the ability of the formed derivatives to cross physiological barriers such as the blood-brain barrier. To the best of our knowledge, we are showing for the first time that (-)-oleocanthal is biochemically transformed to novel products in amino acids/glycine-containing fluids, which were successfully monitored in vitro and in vivo, creating a completely new perspective to understand the well-documented bioactivities of oleocanthal in humans.
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