In silico and In vitro Activity of Leonurus turkestanicus on the Aortic Smooth Muscle Ion Channels

Leonurus turkestanicus is traditionally used for cardiovascular disorders, yet its phytochemical profile and vasorelaxant mechanisms remain insufficiently characterized. In this study, the aqueous extract of L. turkestanicus was analyzed by high-performance liquid chromatography (HPLC), which revealed a rich composition of flavonoids and phenolic acids, including rutin, isoquercitrin, hyperoside, quercetin, apigenin, gallic acid, p-coumaric acid, and ferulic acid. Functional assays in isolated rat aortic rings demonstrated that the extract produced concentration-dependent vasorelaxation against KCl- and phenylephrine-induced contractions. These effects were mediated through inhibition of voltage-dependent L-type calcium channels and receptor-operated calcium channels, as well as through endothelium-dependent nitric oxide signaling. The vasorelaxant action was further supported by additive interactions with verapamil and phentolamine. Molecular docking analyses confirmed that major flavonoids strongly interact with multiple calcium-handling proteins, including L-type and R-type calcium channels, NCX1, SERCA and RyR2, with rutin and hyperoside exhibiting the highest inhibitory affinities. Collectively, these findings indicate that L. turkestanicus exerts vasoprotective effects through a multi-targeted modulation of calcium signaling and endothelial function. The study provides mechanistic evidence supporting the traditional use of L. turkestanicus and identifies its bioactive flavonoids as promising leads for antihypertensive drug development. HIGHLIGHTS Leonurus turkestanicus extract contains abundant flavonoids and phenolic acids (HPLC). Extract produced strong vasorelaxation via inhibition of L-type and ROCC Ca²⁺ channels. Endothelium-dependent nitric oxide signaling contributed to vascular relaxation. Docking showed rutin and hyperoside strongly inhibit Ca²⁺-handling proteins. Findings support turkestanicus as a potential antihypertensive agent. GRAPHICAL ABSTRACT

Ҳали таржима қилинмаган