Cardioprotective potential of oleuropein, hydroxytyrosol, oleocanthal and their combination: Unravelling complementary effects on acute myocardial infarction and metabolic syndrome.

羟基酪醇 油尿苷 心肌梗塞 代谢组学 药理学 医学 化学 生物 生物信息学 心脏病学 生物化学 多酚 抗氧化剂
作者
Andriana Christodoulou,Panagiota Nikolaou,Lydia Symeonidi,K Katogiannis,L. Pechlivani,Θεοδώρα Νίκου,Aimilia Varela,Christina Chania,Stelios Zerikiotis,Panagiotis Efentakis,Dimitrios Vlachodimitropoulos,Nikolaos Katsoulas,Anna Agapaki,Costantinos Dimitriou,Maria Tsoumani,Nikolaos Kostomitsopoulos,Constantinos H. Davos,Alexios Léandros Skaltsounis,Alexandros D. Tselepis,Maria Halabalaki,Ioulia Tseti,Efstathios K. Iliodromitis,Ignatios Ikonomidis,Ana S. Fernandes
出处
期刊:Redox biology [Elsevier]
卷期号:76: 103311-103311
标识
DOI:10.1016/j.redox.2024.103311
摘要

Clinical studies have previously established the role of olive products in cardiovascular disease (CVD) prevention, whilst the identification of the responsible constituents for the beneficial effects is still pending. We sought to assess and compare the cardioprotective potential of oleuropein (OL), hydroxytyrosol (HT), oleocanthal (OC) and oleanolic Acid (OA), regarding Ischemia/Reperfusion Injury (IRI) and CVD risk factors alleviation. The scope of the study was to design a potent and safe combinatorial therapy for high-cardiovascular-risk patients on a bench-to-bedside approach. We evaluated the IRI-limiting potential of 6-weeks treatment with OL, HT, OC or OA at nutritional doses, in healthy and metabolic syndrome (MS)-burdened mice. Three combinatorial regimens were designed and the mixture with preponderant benefits (OL-HT-OC, Combo 2), including infarct sparing and antiglycemic potency, compared to the isolated compounds, was further investigated for its anti-atherosclerotic effects. In vivo experiments revealed that the combination regimen of Combo 2 presented the most favorable effects in limiting infarct size and hyperglycemia, which was selected to be further investigated in the clinical setting in Chronic Coronary Artery Syndrome (CCAS) patients. Cardiac function, inflammation markers and oxidative stress were assessed at baseline and after 4 weeks of treatment with the OL-HT-OC supplement in the clinical study. We found that OL, OC and OA significantly reduced infarct size in vivo compared to Controls. OL exhibited antihyperglycemic properties and OA attenuated hypercholesterolemia. OL-HT-OA, OL-HT-OC and OL-HT-OC-OA combination regimens were cardioprotective, whereas only OL-HT-OC mitigated hyperglycemia. Combo 2 cardioprotection was attributed to apoptosis suppression, enhanced antioxidant effects and upregulation of antioxidant enzymes. Additionally, it reduced atherosclerotic plaque extent in vivo. OL-HT-OC supplement ameliorated cardiac, vascular and endothelial function in the small-scale clinical study. Conclusively, OL-HT-OC combination therapy exerts potent cardioprotective, antihyperglycemic and anti-atherosclerotic properties in vivo, with remarkable and clinically translatable cardiovascular benefits in high-risk patients.

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