Olea europaea L. fruit is a peculiar vegetal matrix containing high levels of fatty acids (98–99% of the total weight of extra-virgin olive oil, EVOO) and low quantities (1–2%) of phenolics, phytosterols, tocopherols, and squalene. Among these minor components, phenolics are relevant molecules for human health. This review is focused on their beneficial activity, in particular of hydroxytyrosol (HT), oleuropein (OLE), oleocanthal (OLC), and lignans found in EVOO, olive oil by-products and leaves. Specifically, the cardioprotective properties of the Mediterranean diet (MD) related to olive oil consumption, and the biological activities of polyphenols recovered from olive oil by-products and leaves were described. Recent European projects such as EPIC (European Prospective Investigation into Cancer and Nutrition) and EPICOR (long-term follow-up of antithrombotic management patterns in acute coronary syndrome patients) have demonstrated the functional and preventive activities of EVOO showing the relation both between cancer and nutrition and between consumption of EVOO, vegetables, and fruit and the incidence of coronary heart disease. The data reported in this review demonstrate that EVOO, one of the pillars of the MD, is the main product of Olea europaea L. fruits; leaves and by-products are secondary but precious products from which bioactive compounds can be recovered by green technologies and reused for food, agronomic, nutraceutical, and biomedical applications according to the circular economy strategy.

Growing scientific literature data suggest that the intake of natural bioactive compounds plays a critical role in preventing or reducing the occurrence of human chronic non-communicable diseases (NCDs). Oleuropein, the main phenolic component of Olea europaea L., has attracted scientific attention for its several health beneficial properties such as antioxidant, anti-inflammatory, cardio- and neuro-protective, and anti-cancer. This article is a narrative review focused on the current literature concerning the effect of oleuropein in NCDs, such as neuro- and cardiovascular diseases, diabetes mellitus, chronic kidney diseases, and cancer, by its putative antioxidant and anti-inflammatory activity, but also for its other peculiar actions such as an autophagy inducer and amyloid fibril growth inhibitor and, finally, for its anti-cancer effect. Despite the increasing number of published studies, looking at the beneficial effects of oleuropein, there is limited clinical evidence focused on the benefits of this polyphenol as a nutraceutical product in humans, and many problems are still to be resolved about its bioavailability, bioaccessibility, and dosage. Thus, future clinical randomized trials are needed to establish the relation between the beneficial effects and the mechanisms of action occurring in the human body in response to the intake of oleuropein.

This review reports in detail the cellular and molecular mechanisms which regulate the bone remodeling process in relation to oxidative stress (OS), inflammatory factors, and estrogen deficiency. OS is considered an important pathogenic factor of osteoporosis, inducing osteocyte apoptosis and varying levels of specific factors, such as receptor activator κB ligand (RANKL), sclerostin, and, according to recent evidence, fibroblast growth factor 23, with consequent impairment of bone remodeling and high bone resorption. Bone loss increases the risk of fragility fractures, and the most commonly used treatments are antiresorptive drugs, followed by anabolic drugs or those with a double effect. In addition, recent data show that natural antioxidants contained in the diet are efficient in preventing and reducing the negative effects of OS on bone remodeling and osteocytes through the involvement of sirtuin type 1 enzyme. Indeed, osteocytes and some of their molecular factors are considered potential biological targets on which antioxidants can act to prevent and reduce bone loss, as well as to promote bone anabolic and regenerative processes by restoring physiological bone remodeling. Several data suggest including antioxidants in novel therapeutic approaches to develop better management strategies for the prevention and treatment of osteoporosis and OS-related bone diseases. In particular, anthocyanins, as well as resveratrol, lycopene, oleuropein, some vitamins, and thiol antioxidants, could have protective and therapeutic anti-osteoporotic effects.

Oleuropein aglycone induces autophagy via the AMPK/mTOR signalling pathway: a mechanistic insight

Aims: Oxidative stress and mitochondrial dysfunction participate together in the development of heart failure (HF). mRNA levels of monoamine oxidase-A (MAO-A), a mitochondrial enzyme that produces hydrogen peroxide (H ₂ O ₂ ), increase in several models of cardiomyopathies. Therefore, we hypothesized that an increase in cardiac MAO-A could cause oxidative stress and mitochondrial damage, leading to cardiac dysfunction. In the present study, we evaluated the consequences of cardiac MAO-A augmentation on chronic oxidative damage, cardiomyocyte survival, and heart function, and identified the intracellular pathways involved. Results: We generated transgenic (Tg) mice with cardiac-specific MAO-A overexpression. Tg mice displayed cardiac MAO-A activity levels similar to those found in HF and aging. As expected, Tg mice showed a significant decrease in the cardiac amounts of the MAO-A substrates serotonin and norepinephrine. This was associated with enhanced H ₂ O ₂ generation in situ and mitochondrial DNA oxidation. As a consequence, MAO-A Tg mice demonstrated progressive loss of cardiomyocytes by necrosis and ventricular failure, which were prevented by chronic treatment with the MAO-A inhibitor clorgyline and the antioxidant N-acetyl-cystein. Interestingly, Tg hearts exhibited p53 accumulation and downregulation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a master regulator of mitochondrial function. This was concomitant with cardiac mitochondrial ultrastructural defects and ATP depletion. In vitro , MAO-A adenovirus transduction of neonatal cardiomyocytes mimicked the results in MAO-A Tg mice, triggering oxidative stress-dependent p53 activation, leading to PGC-1α downregulation, mitochondrial impairment, and cardiomyocyte necrosis. Innovation and Conclusion: We provide the first evidence that MAO-A upregulation in the heart causes oxidative mitochondrial damage, p53-dependent repression of PGC-1α, cardiomyocyte necrosis, and chronic ventricular dysfunction. Antioxid. Redox Signal. 18, 5–18.