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


  • Agung Endro Nugroho Faculty of Pharmacy, Universitas Gadjah Mada
  • Puguh Noviarsito Postgraduate Programme, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia Pharmacy Study Programme, Faculty of Medicine and Health Sciences, Universitas Muhammadiyah Yogyakarta, Yogyakarta Indonesia
  • Sugeng Riyanto Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia



Marmin is a coumarin derivative compounds isolated from the bark and roots of Aegle Marmelos Correa. Previously, ethanolic extract of leaves of Aegle Marmelos Correa on isolated ileum showed antagonism effect on the contraction induced by histamine. Besides H1 receptor, there is also muscarinic acetylcholine (AChM)receptors involved in the mechanism of ileum contraction. Marmin is predicted to antagonize on AChM3 receptors.This study aimed to determine the effect of marmin on smooth muscle contraction of isolated guinea pig ileum induced by metacholine, an agonist of AChM3 receptor. The method in the study were in vitro (isolated organ) and in silico (docking PLANTS). In the in vitro study, marmin exhibited a competitive antagonists effect at the concentration of 100 μM (pA2 value of 1,728) on the AChM3 receptors. Reversibility assay on AChM3 receptors showed that by washing the ileum with Tyrode buffer every 6 minutes for 30 minutes, the bond of marmin to the receptor was still not completely detached. In the in silico study, marmin was observed to be bound to AchM3 receptors (docking score: -102.086). Marmin bond was weaker than that of native ligand of AChM3 receptor (tiotropium, docking score: -115.107), however, stronger than that of AChM3 receptor agonist and antagonist. Based on the results, we conclude that marmin have a competitive antagonist activity on AChM3 receptor.


Maity, P., Hansda, D., Bandyopadhyay, U. dan Mishra, D.K., 2009, Biological activities of crude extracts and chemical constituents of Bael, Aegle marmelos (L.) Corr, Indian J. Exp. Biol, 47(11), 849-861.

Arul, V., Miyazaki, S., dan Dhananjayan, R., 2004, Mechanisms of the contractile effect of the alcoholic extract of Aegle marmelos Corr. on isolated guinea pig ileum and tracheal chain, Phytomedicine, 11(7-8), 679-83.

Riyanto, S., 2003, Phytochemical Studies and Bioactivity Tests of Murraya paniculata Jack., Aegle marmelos Correa and Zingiber Amaricans Blume, Dissertasi, University Putra Malaysia.

Nugroho, A.E., Riyanto, S., Sukari, M.A., Maeyama, K., 2010, Effects of Skimmianine, a quinoline alkaloid of Aegle marmelos Correa roots, on the histamine release from mast cells, Journal of Basic and Applied Sciences, 6(2): 141-148.

Nugroho, A.E., Riyanto, S., Sukari, M.A., Maeyama, K., 2011a, Effects of aegeline, a main alkaloid of Aegle marmelos Correa leaves, on the histamine release from mast cells, Pakistan Journal of Pharmaceutical Science (Pubmed), 24 (3) : 359-367.

Nugroho, A.E., Riyanto, S., Sukari, M.A., Maeyama, K., 2011b, Anti-allergic effects of Marmin, a coumarine isolated from Aegle marmelos Correa: In vitro study, International Journal of Phytomedicine, 3(1), 84-97.

Nugroho, A.E., Anas, Y., Arsito, P.N., Wibowo, J.T., Riyanto, S., Sukari, M.A., 2011c, Effects of marmin, a compound isolated from Aegle marmelos correa, on contraction of the guinea pig-isolated trachea, Pakistan Journal of Pharmaceutical Sciences, 24 (4), 427-433

Rang HP, Dale MM, Ritter JM, Moore PK. (2003). Pharmacology. 5th Ed. Churchill Livingstone, Sydney; pp.693-698.

Sanders, K.M., 2001, Invited Review: Mechanisms of Calcium Handling in Smooth muscles, J.Appl .Physiol, 91: 1438-1449

Gosens, R., Zaagsma, J, Meurs, H. and Halayko, A.J., 2006, Muscarinic Receptor Signaling in the Pathophysiology of Asthma and COPD, Respir.Res.7(1) : 73-87.