Research paperMediterranean products as promising source of multi-target agents in the treatment of metabolic syndrome
Graphical abstract
Introduction
Metabolic syndrome (MetS) describes a collection of metabolic abnormalities that are associated with visceral adiposity. This condition is diagnosed by the simultaneous occurrence of at least 3 of these 5 factors: abdominal obesity, atherogenic dyslipidaemia associated with low-density lipoprotein (LDL) and/or high-density lipoprotein (HDL), elevated triglycerides (TG), hypertension, atherosclerotic cardiovascular diseases (CVDs) and fasting plasma glucose of at least 100 mg/dl [1]. Disease patterns associated with MetS can be chronic, debilitating, and lethal. MetS is clearly a multifactorial pathology, in which several pathways are involved in the metabolic disorder. Although the multi-factorial nature is evident, nowadays available drugs individually act on each aspect of the disease. The identification of common pathways as drug targets surely could be useful to figure out molecules with multi-target profile, able to interact with them to contrast the disorder.
In recent decades, the paradigm of "one drug, one activity, one disease" has dominated the drug discovery process in Western Medicine. However, this idea has been changed through the discovery of multi-target bioactive compounds, in which the same drug can simultaneously exert its effects through interactions with multiple targets, by opening new areas for research. In particular, a wide variety of molecules derived from natural products have been evaluated for their multiple biological effects, such as analgesic, anti-proliferative, anti-inflammatory, anti-bacterial and anti-oxidant effects, among others [2].
This review highlights some of the recent findings regarding different multi-target natural bioactive compounds, with particular attention to the products that characterize the Mediterranean diet (MedDiet). Indeed, emerging evidence underlines the protective effect exerted by the MedDiet on the different factors of MetS [3]. In particular, the anti-oxidant and anti-inflammatory properties of MedDiet food such as olive oil, nuts, vegetables and wine, have been widely documented and their beneficial properties seem to be connected to their phytochemical components. In this review, we presented a brief background on the isolated natural compounds extracted from Mediterranean products, their structures, their multi-target activities and their postulated mechanism of action. Our aim is to highlight the principal evidence linking the effectiveness of the MedDiet in preventing or delaying the physiopathological components accountable for MetS onset. Therefore, the main bioactive compounds contained in typical MedDiet foods are examined, by focusing on their activity in the regulation of mechanisms involved in key MetS features, such as insulin resistance (IR), endothelial dysfunctions, inflammatory response, oxidative stress and dyslipidaemia.
Section snippets
Polypharmacology as innovative approach
The observation that several drugs explicate their pharmacological effect through the interaction with multiple targets is shifting the drug discovery paradigm from the one target–one drug model to a more effective multiple-target approach, a phenomenon called polypharmacology. In this context, the development of selective molecules acting specifically on a single molecular target, according to the paradigm ‘single keys for specific locks’, has been overcome and is moving towards the
Mediterranean area products
The MedDiet is a dietary pattern followed by people living in the Mediterranean Sea basin and it was firstly described by Keys in 1960s [7]. It is characterized by three important features: (a) daily consumption of non-refined cereals and products (e.g., whole grain bread, whole grain pasta, and brown rice), fresh fruits, vegetables, nuts, low-fat dairy products, and olive oil as principal source of lipids; (b) moderate intake of wine (especially red wine); (c) regular physical activity.
Olive
The olive tree (Olea Europea L.) is a subtropical species typical of the Mediterranean basin. It concerns an evergreen tree, with narrow silvery leaves and small white flowers [11]. At the begging, the cultivation of olive tree involved the eastern Mediterranean and subsequently, it was expanded in Southern Europe and North Africa [11]. The olive fruit is a drupe, oval shape and consists mainly in two parts: pulp and seed. From the pulp is extracted at least 98% of olive oil [12]. The
General overview of the main molecular targets
In the light of the multi-target properties of the bioactive compounds of MetDiet involved in the prevention and treatment of the MetS, in Table 5, we summarize the main molecular targets and biologically mechanisms responsible for their protective effects.
Conclusion
The MetS is a pathological state identified by the coexistence of different dysmetabolic events including T2DM, obesity, hypertension, dyslipidaemia and cardiovascular complications, thus representing one of the major health risks of the modern age. In fact, even the MetS initially have appeared in the Western world, due to the diffusion of the Western lifestyle across the globe, now it has developed into a now worldwide problem. Once diagnosed, it is crucial to intervene promptly through the
Author contributions
The manuscript was written through the contributions of all authors. All authors have given approval to the final version of the manuscript.
Donatella Bagetta, Annalisa Maruca and Antonio Lupia contributed equally.
Founding source
The authors acknowledge the PRIN 2017 research project “Novel anticancer agents endowed with multi-targeting mechanism of action” [Project n. 201744BN5T].
Declaration of competing interest
The authors declare no conflicts of interest.
Acknowledgements
We thank the European Cooperation in Science and Technology (COST Action) [CA15135; multi-target paradigm for innovative ligand identification in the drug discovery process] for the support.
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These authors contributed equally.