Naturally Occurring H₂S-Donors in Vascular Diseases

Hydrogen sulfide (H₂S) is an endogenous gasotransmitter able to exert a pivotal role in different organs and systems, strongly influencing cardiovascular health. It is an endowed antioxidant, a vasorelaxant, and has cardioprotective properties, thanks to the activation of different classes of potassium channels and the interaction with several pathways including those involving sirtuins, nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor kappa B (NF-κB), and nitric oxide (NO) production. Alterations in the homeostasis of H₂S represent an etiopathogenetic factor in the onset and progression of cardiovascular diseases, such as hypertension, atherosclerosis, and vascular diabetic complications, highlighting the therapeutic potential of exogeneous H₂S-donors in H₂S-poor diseases. Several natural H₂S-donor compounds, or their precursors, derive from plants belonging to the Alliaceae (e.g., garlic and onion), Brassicaceae (e.g., broccoli and rocket salad), or Moringaceae (e.g., moringa) families. Preclinical studies demonstrated the antioxidant, vasoprotective, and anti-hypertensive properties of both plant extracts and isolated polysulfides or isothiocyanates (ITCs). In fact, polysulfides and ITCs are able to exert vascular effects superimposable to those induced by H₂S. Preclinical and clinical studies successfully demonstrated that garlic extracts decrease systolic and diastolic blood pressure and contrast endothelial dysfunction and atherosclerosis. Similarly, preclinical studies highlighted the anti-inflammatory, anti-hypertensive, and vasoprotective properties of ITCs. However, clinical studies only demonstrated the improvement of the lipid profile in healthy patients, with no effects on systolic or diastolic blood pressure. Taken together, these findings suggest that natural H₂S-donors could restore H₂S homeostasis, therefore preventing and/or contrasting cardiovascular diseases.