Oleocanthal is a secoiridoid found in olive oil, which lately gained great scientific interest due to its important pharmacological spectrum and biological properties. However, limited data exist on the metabolic fate of oleocanthal in vivo, a commonly underestimated aspect in natural products research. Especially, its pharmacokinetic (PK) characteristics have never been described so far. Thus, in the current study, a mouse-based protocol was designed, and oleocanthal was administered intraperitoneally in a standard dose of 5 mg/kg. In order to determine the PK parameters of oleocanthal or its metabolites, plasma samples were collected at 10 time points. Extraction and analysis protocols were developed and applied for the recovery and detection of oleocanthal in plasma, as well as the identification of its metabolites, using LC-HRMS/MS. Oleocanthal was not detected, proving the short lifetime of the compound in vivo, and 13 metabolites were identified. Among them, oleocanthalic acid and tyrosol sulfate were proposed as oleocanthal’s biomarkers, in vivo. This is the first report associating oleocanthalic acid with oleocanthal administration in vivo, while its PK parameters, Tmax (T0) and Cmax (926 μg/mL), were also determined. The current study enlightens bioavailability and metabolism aspects of oleocanthal and suggests the association of specific metabolites with the biological effects attributed to oleocanthal administration. More studies are needed to give better insights into the metabolism and the mechanism of action of secoiridoids as well as to respond to identification challenges related to secoiridoid in vivo setups.

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油橄榄的药代动力学和代谢研究

油橄榄素是在橄榄油中发现的环烯醚萜类化合物，由于其重要的药理学谱和生物学特性，最近引起了极大的科学兴趣。然而，关于油橄榄在体内的代谢命运的数据有限，这是天然产物研究中通常被低估的一个方面。特别是，其药代动力学（PK）特性迄今为止从未被描述过。因此，在本研究中，设计了基于小鼠的方案，并以 5 mg/kg 的标准剂量腹腔内施用油橄榄。为了确定油橄榄或其代谢物的 PK 参数，在 10 个时间点采集血浆样本。开发了提取和分析方案，并使用 LC-HRMS/MS 来回收和检测血浆中的油棘醛，以及鉴定其代谢物。未检测到油橄榄醛，证明该化合物在体内的寿命较短，并鉴定出 13 种代谢物。其中，油棘酸和硫酸酪醇被提议作为油棘醛的体内生物标志物。这是第一份将油棘脂酸与油棘脂体内给药相关联的报告，同时还测定了其 PK 参数 Tmax (T0) 和 Cmax (926 μg/mL)。目前的研究揭示了油橄榄的生物利用度和代谢方面，并表明特定代谢物与油橄榄施用的生物效应之间的关联。需要更多的研究来更好地了解环烯醚萜的代谢和作用机制，并应对与环烯醚萜体内设置相关的鉴定挑战。