Unveiling the calcium channel blocking potential of Suaeda fruticosa : From ex vivo studies to molecular docking

Suaeda fruticosa is a widely distributed plant in Pakistan which has been traditionally used as a remedy for constipation, dyspnoea, headache, nausea, neurosis and vertigo.

The present study aimed to scientifically validate the traditionally claimed medicinal properties of Suaeda fruticosa.

The experiment involved the preparation of a 70% ethanolic extract of Suaeda fruticosa (Sf.Cr), which was tested ex-vivo in an isolated rabbit jejunum preparation for spasmolytic activity. Moreover, the crude extract was tested on isolated tracheal and aorta preparations to evaluate the effects.

Sf.Cr dose-dependently relaxed the jejunum and inhibited K+(80 mM)-induced contractions with EC50 value of 0.229 mg/ml and 0.095 mg/ml, respectively. Further, the Sf.Cr caused a rightward shift in Ca2+ concentration response curves (CRCs), similar to verapamil. So, calcium channel-blocking and anticholinergic actions were responsible for the antispasmodic (anti-diarrhoeal) effect. Sf.Cr produced inhibition of carbachol (1 µM)- and K+(80 mM)-induced contractions in isolated rabbit tracheal tissues with EC50 values of 0.8339 mg/ml and 1.022 mg/ml, respectively. Sf. Cr also completely abolished the Phenylephrine (1 µM)- and K+(80 mM)-induced constrictions in isolated rabbit aortic rings, with EC50 values of 0.9448 mg/ml and 0.2026 mg/ml, respectively. Molecular docking against calmodulin (PDB ID: 6M7H) showed that 3-hydroxy-2-quinolinone attained the highest glide score (-6.742 kcal.mol-¹), establishing hydrogen bonding and Pi-Pi stacking interactions with MET124 and PHE92, surpassing the binding affinity of the standard drug verapamil (-5.464 kcal.mol-¹). SwissADME profiling showed that all identified phytoconstituents complied with Lipinski's rule of five, exhibited high gastrointestinal absorption and were predicted to cross the blood-brain barrier, supporting their oral bioavailability as drug candidates.

These findings collectively established Sf.Cr as a source of non-specific calcium channel-blocking phytochemicals with potential for developing antispasmodic, bronchodilator, and vasorelaxant agents.