Alkaloids as Vasodilator Agents: A Review

Abstract

The pathophysiology of hypertension is often associated with endothelial dysfunction and the impairment of endothelium-dependent vasodilation mechanisms, as well as alterations in vascular smooth muscle (VSM) tone. Natural products, particularly alkaloids, have received increased attention in the search for new vasodilator agents. This review aims to summarize the noteworthy results from ex-vivo and in-vitro studies that explored the vasodilatory effects of some selected alkaloids (Berberine, Sinomenine, (S)-Reticuline, Neferine, Nuciferine, Villocarine A, 8-Oxo-9-Dihydromakonakine, Harmaline, Harman, and Capsaicin) and the underlying mechanisms implicated. The results obtained from the literature revealed that these selected alkaloids exhibited vasodilation in various vascular models, including mesenteric, carotid, and coronary arteries, thoracic aorta, and cultured HUCECs and VSMCs. Furthermore, most of these alkaloids induced vasodilation through endothelium- dependent and endothelium-independent mechanisms, which were primarily mediated by activating eNOS/NO/sGC/cGMP pathway, opening various potassium (K⁺) channels, or modulating calcium (Ca2⁺) channels. Additionally, several alkaloids exerted vasodilatory effects through multiple mechanism pathways. Moreover, different alkaloids demonstrated the ability to protect endothelial function by reducing oxidative stress, endoplasmic reticulum and inflammation. In conclusion, this class of secondary metabolites holds interesting therapeutic potential in the prevention and treatment of cardiovascular diseases (CVD), particularly hypertension.

Keywords: Vasodilator agents; alkaloids; calcium (Ca2+) channels; eNOS/NO/sGC/cGMP pathway; hypertension; potassium (K+) channels; vascular endothelium; vascular smooth muscle.