Preventive and inhibitory effects of Salacia on sustained contraction of vascular smooth muscle cells and characterization of the active compounds

Sustained contraction of vascular smooth muscles can abruptly restrict blood flow, leading to ischemia. While mild, prolonged contractions may cause dizziness and migraines, severe vasoconstriction (vasospasm) can result in cerebral or myocardial infarction and may be fatal. Sphingosylphosphorylcholine (SPC) is a known inducer of pathological sustained contraction that occurs independently of Ca²⁺-dependent mechanisms. Although lipid-soluble dietary compounds have been reported to inhibit SPC-induced contractions, their clinical utility is limited by poor suitability for aqueous formulations and a tendency to accumulate in membranes and adipose tissue. In this study, we sought to identify water-soluble compounds that selectively inhibit pathological sustained contraction without impairing Ca²⁺-dependent vascular contraction. We focused on <i>Salacia</i>, a medicinal plant extensively studied for its metabolic effects, but whose vascular actions remain poorly characterized. Extracts from both aboveground (stems and trunks) and belowground (roots) parts of <i>Salacia</i>, applied either before or during SPC exposure, significantly inhibited SPC-induced sustained contraction. The active compounds were identified as 3,4-dihydroxybenzoic acid (3,4-DHBA), <i>trans</i>-3-, <i>trans</i>-4-, and <i>trans</i>-5-caffeoylquinic acids (CQAs), <i>ortho</i>-hydroxybenzoic acid (<i>o</i>-HBA), and <i>para</i>-HBA (<i>p</i>-HBA). Inhibitory potency followed the order 3,4-DHBA ≈ CQA > HBA. Notably, 3,4-DHBA and CQAs readily permeated vascular endothelial cells to reach smooth muscle, and their inhibitory effects were synergistically enhanced when 3,4-DHBA was present in excess. These findings suggest that water-soluble compounds from <i>Salacia</i> may prevent or attenuate SPC-induced vasospasm and its associated severe vascular diseases.