Biomol Ther.  2019 May;27(3):290-301. 10.4062/biomolther.2019.007.

Involvement of a Novel Organic Cation Transporter in Paeonol Transport Across the Blood-Brain Barrier

Affiliations
  • 1College of Pharmacy, Sookmyung Women's University, Seoul 04310, Republic of Korea. yskang@sm.ac.kr

Abstract

Paeonol has neuroprotective function, which could be useful for improving central nervous system disorder. The purpose of this study was to characterize the functional mechanism involved in brain transport of paeonol through blood-brain barrier (BBB). Brain transport of paeonol was characterized by internal carotid artery perfusion (ICAP), carotid artery single injection technique (brain uptake index, BUI) and intravenous (IV) injection technique in vivo. The transport mechanism of paeonol was examined using conditionally immortalized rat brain capillary endothelial cell line (TR-BBB) as an in vitro model of BBB. Brain volume of distribution (V(D)) of [³H]paeonol in rat brain was about 6-fold higher than that of [¹â´C]sucrose, the vascular space marker of BBB. The uptake of [³H]paeonol was concentration-dependent. Brain volume of distribution of paeonol and BUI as in vivo and inhibition of analog as in vitro studies presented significant reduction effect in the presence of unlabeled lipophilic compounds such as paeonol, imperatorin, diphenhydramine, pyrilamine, tramadol and ALC during the uptake of [³H]paeonol. In addition, the uptake significantly decreased and increased at the acidic and alkaline pH in both extracellular and intracellular study, respectively. In the presence of metabolic inhibitor, the uptake reduced significantly but not affected by sodium free or membrane potential disruption. Similarly, paeonol uptake was not affected on OCTN2 or rPMAT siRNA transfection BBB cells. Interestingly. Paeonol is actively transported from the blood to brain across the BBB by a carrier mediated transporter system.

Keyword

Blood-brain barrier; Paeonol; Novel organic cationic transporter system; Brain transport; TR-BBB cells

MeSH Terms

Animals
Blood-Brain Barrier*
Brain
Carotid Arteries
Carotid Artery, Internal
Central Nervous System
Diphenhydramine
Endothelial Cells
Hydrogen-Ion Concentration
In Vitro Techniques
Membrane Potentials
Perfusion
Pyrilamine
Rats
RNA, Small Interfering
Sodium
Tramadol
Transfection
Diphenhydramine
Pyrilamine
RNA, Small Interfering
Sodium
Tramadol
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