*Review* **Selected Plant-Derived Polyphenols as Potential Therapeutic Agents for Peripheral Artery Disease: Molecular Mechanisms, Efficacy and Safety**

**Guglielmina Froldi \* and Eugenio Ragazzi**

Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35131 Padova, Italy **\*** Correspondence: g.froldi@unipd.it

**Abstract:** Vascular diseases, such as peripheral artery disease (PAD), are associated with diabetes mellitus and a higher risk of cardiovascular disease and even death. Surgical revascularization and pharmacological treatments (mainly antiplatelet, lipid-lowering drugs, and antidiabetic agents) have some effectiveness, but the response and efficacy of therapy are overly dependent on the patient's conditions. Thus, the demand for new cures exists. In this regard, new studies on natural polyphenols that act on key points involved in the pathogenesis of vascular diseases and, thus, on PAD are of great urgency. The purpose of this review is to take into account the mechanisms that lead to endothelium dysfunction, such as the glycoxidation process and the production of advanced glycation endproducts (AGEs) that result in protein misfolding, and to suggest plant-derived polyphenols that could be useful in PAD. Thus, five polyphenols are considered, baicalein, curcumin, mangiferin, quercetin and resveratrol, reviewing the literature in PubMed. The key molecular mechanisms and preclinical and clinical studies of each selected compound are examined. Furthermore, the safety profiles of the polyphenols are outlined, together with the unwanted effects reported in humans, also by searching the WHO database (VigiBase).

**Keywords:** baicalein; curcumin; mangiferin; quercetin; resveratrol; diabetes mellitus; endothelial dysfunction; peripheral artery disease; polyphenols; cardiovascular diseases
