β(2)-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 β(2)-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 E(max) of terbutaline, whilst the EC(50) for 6-MKG was at least half than that of terbutaline. The β(2)-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 β(2)-adrenoceptors agonistic property of the compound. In in silico docking studies, 6-MKG bound to rat β(2)-adrenoceptors with low ∆G(bind) value (-11.53±0.06 kcal/mol) and it interacted with four residues of the active site (Asp(113), Asn(312), Cys(191)and Tyr(316)). It is concluded that 6-MKG exerts weak β(2)-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.