**1. Introduction**

Non-communicable diseases, such as cardiovascular diseases, are continuously monitored and investigated for prevalence, pathophysiology, outcome and prevention [1]; however, the impact of peripheral artery disease (PAD) is not adequately considered. Atherosclerotic occlusive disease of the lower extremities affects approximately 10% of people in their 60s and 70s, and approximately 20% of individuals over the age of 80 years [2,3]. Patients with diabetes mellitus (DM), those who smoke, the elderly and those affected by cardiovascular diseases are mainly at risk of encountering PAD [2,4]. A calculator to predict the lifetime risk of PAD is available online [5].

There is convincing evidence to support the fact that the primary pathophysiology of PAD is triggered by the obstruction of atherosclerotic plaques of the lower extremities causing a consequent decrease in blood flow (ankle brachial index, ABI ≤ 0.9) [6]. Leg pain during exercise due to poor blood flow (intermittent claudication) is a major symptom of PAD; in fact, increasing blood supply to the compromised limb after surgical revascularization can improve symptoms and hemodynamic parameters in the patients [7]. Primarily, antiplatelet therapy is recommended to reduce cardiovascular complications in PAD, whereas β-adrenergic inhibitors should be used with caution, if clinically indicated [8]. Other agents used in patients with PAD are standard lipid-lowering therapies, mainly the administration of statins [8]. In general, several therapeutic agents can improve endothelial vasodilator function and insulin resistance: pioglitazone, metformin, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II-receptor antagonists

**Citation:** Froldi, G.; Ragazzi, E. Selected Plant-Derived Polyphenols as Potential Therapeutic Agents for Peripheral Artery Disease: Molecular Mechanisms, Efficacy and Safety. *Molecules* **2022**, *27*, 7110. https:// doi.org/10.3390/molecules27207110

Academic Editor: Nour Eddine Es-Safi

Received: 30 September 2022 Accepted: 18 October 2022 Published: 21 October 2022

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(AT1-receptor blockers) [8]. Additionally, various vasoactive drugs could be used to treat symptoms, such as improving walking distances [2]. Furthermore, propionyl-L-carnitine has been suggested to alleviate PAD symptoms through a metabolic pathway, thus improving exercise performance [9–11]. In addition, gene therapy using encoding genes of various types of growth factors is at the beginning stage [12].

Although these approaches have some success, the demand for other types of remedies remains unmet, and, for this reason, a large quantity of food supplements are commercially proposed, often without scientific evidence, to decrease PAD symptoms.
