Mitragynine and 7-hydroxymitragynine: In vitro blood-brain barrier permeability studies

Abstract

Event Abstract Back to Event Mitragynine and 7-hydroxymitragynine: In vitro blood-brain barrier permeability studies Mahathir Mohd Uzid1*, Nur Aziah Hanapi1, Sharif Mahsufi Mansor1 and Siti Rafidah Yusof1 1 Universiti Sains Malaysia, Centre for Drug Research, Malaysia Mitragynine (MG), the major alkaloid present in the leaves of M. speciosa is reported to be responsible for opioid agonistic activity and 7-hydroxymitragynine (7-OH MG) a minor derivative, possessed much more potent opioid activity compared to mitragynine and morphine. Although the central nervous system activities of MG and 7-OH MG are widely studied, research on their blood-brain barrier (BBB) permeability is still lacking. In this study, MG and 7-OH MG permeability was studied using in vitro BBB model from primary porcine brain endothelial cells (PBECs). The PBECs showed restrictive tight junction with average transendothelial electrical resistance of 470.23 ± 21.77 Ω.cm2. Permeability assays were conducted from apical-to-basal (A-B; blood-to-brain) and basal-to-apical (B-A; brain-to-blood) directions to determine MG and 7-OH MG BBB mechanisms. Sodium fluorescein was used as parallel tight junction permeability marker. To determine interaction of MG and 7-OH MG with efflux transporters, permeability assay (A-B direction) was conducted in presence of efflux transporter inhibitor verapamil (50 µM). From the results, MG showed higher A-B permeability (Papp = 35.04 × 10-6 cm/s) compared to B-A (Papp = 21.42 × 10-6 cm/s) with efflux ratio (B-A/ A-B) of 0.61, suggesting net permeability of influx into the brain. In comparison, 7-OH MG showed lower A-B (Papp = 15.31 × 10-6 cm/s) compared to B-A (Papp = 21.31 × 10-6 cm/s) permeability with efflux ratio (B-A/ A-B) of 1.39, suggesting net permeability of efflux from the brain into the blood circulation. Presence of verapamil caused significant increase in A-B permeability of 7-OH MG (Papp = 46.62 × 10-6 cm/s), which indicates interaction of 7-OH MG with efflux transporters particularly the ATP-binding cassette transporters. This study is the first to report on mechanisms of MG and 7-OH MG BBB permeability, using primary brain endothelial cell as a model. Keywords: Blood-Brain Barrier, Nervous System, opioid, in vitro, mitragynine Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Mohd Uzid M, Hanapi N, Mansor S and Yusof S (2016). Mitragynine and 7-hydroxymitragynine: In vitro blood-brain barrier permeability studies. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00145 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Mr. Mahathir Mohd Uzid, Universiti Sains Malaysia, Centre for Drug Research, Gelugor, Pulau Pinang, Malaysia, mahathirmu@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Mahathir Mohd Uzid Nur Aziah Hanapi Sharif Mahsufi Mansor Siti Rafidah Yusof Google Mahathir Mohd Uzid Nur Aziah Hanapi Sharif Mahsufi Mansor Siti Rafidah Yusof Google Scholar Mahathir Mohd Uzid Nur Aziah Hanapi Sharif Mahsufi Mansor Siti Rafidah Yusof PubMed Mahathir Mohd Uzid Nur Aziah Hanapi Sharif Mahsufi Mansor Siti Rafidah Yusof Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.