Marmin of Aegle Marmelos Correa Antagonizes AChM3 Receptors: In Silico and In Vitro Studies on Isolated-Guinea Pig Illeum Smooth Muscle.

A previous study has shown that ethanolic extract of leaves of A. marmelos Correa on isolated ileum had an antagonistic effect on the contraction induced by histamine. Apart from H1 receptors, muscarinic acetylcholine (AChM) receptors are also involved in the mechanism of ileum contraction. Marmin is predicted to antagonize the AChM3 receptors. This study was aimed at determining the effect of marmin on smooth muscle contraction of isolated guinea pig ileum induced by metacholine, an AChM3 agonist. The methods used were in vitro (isolated organ) and in silico (docking PLANTS) studies. In the in vitro study, marmin exhibited a competitive antagonistic effect at a concentration of 100 μM (pA2 = 1,728) on the AChM3 receptors. A reversibility assay of the AChM3 receptors showed that by washing the ileum with Tyrode's buffer every 6 minutes for 30 minutes, the bond of marmin to the receptors was still not completely detached. In the in silico study, marmin was observed to be bound to the AchM3 receptors (docking score: -102.086). The marmin bond was weaker than that of the native ligand of the AChM3 receptors (tiotropium, docking score: -115.107), but stronger than that of the AChM3 receptor agonist and antagonist. Based on the results, we conclude that marmin has competitive antagonist activity on AChM3 receptors. [ABSTRACT FROM AUTHOR]