β2-Adrenergic activity of 6-methoxykaempferol-3-O-glucoside on rat uterus: In vitro and in silico studies

6-Methoxykaempferol-3-O-glucoside (6-MKG) was isolated from a Sudanese herb (El-hazha). The pharmacological effects of 6-MKG were tested on isolated non-pregnant or late-pregnant rat uteri in vitro, whilst docking studies were carried out modelling of the binding of 6-MKG to the rat β2-adrenoceptor in silico. In vitro studies revealed that 6-MKG was able to relax both the non-pregnant and the late-pregnant uterine contractility with 50% of the Emax of terbutaline, whilst the EC50 for 6-MKG was at least half than that of terbutaline. The β2-adrenoceptors antagonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol(ICI118,551) competitively antagonised the relaxing effect of 6-MKG. Radioligand binding and cAMP studies confirmed the β2-adrenoceptors agonistic property of the compound. In in silico docking studies, 6-MKG bound to rat β2-adrenoceptors with low ∆Gbind value (− 11.53 ± 0.06 kcal/mol) and it interacted with four residues of the active site (Asp113, Asn312, Cys191and Tyr316). It is concluded that 6-MKG exerts weak β2-adrenoceptor agonistic activity and can be considered a natural compound with potential therapeutic significance in the field of premature pregnant uterine contractions and asthmatic problems.

Research highlights
► 6-methoxykaempferol-3-O-glucoside (6-MKG) was isolated and identified early (2004).
► Its pharmacological profile remains controversial.
► This study aimed to proof and determine the pharmacological profile of 6-MKG by in silico - in vitro techniques using β2-adrenoceptor as main target.
► The present study revealed that 6-MKG possesses weak β2-adrenoceptor agonistic activity.
► 6-MKG was with therapeutic potential for premature labour inhibition and asthma treatment.