Borneol and Α-asarone as adjuvant agents for improving blood–brain barrier permeability of puerarin and tetramethylpyrazine by activating adenosine receptors

Drug Delivery

Jie-Min Wang¹  Jun-Yong Wu¹  Xin-Yi Liu¹  Tian-Tian Tang¹  Yong-Jiang Li¹  Da-Xiong Xiang¹  Yi-Yun Hu¹  Xiong-Bin Hu¹  Le Yang¹ 

[1] Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China;Institute of Clinical Pharmacy, Central South University, Changsha, Hunan, China;Hunan Provincial Engineering Research Center of Translational Medicine and Innovative Drug, Changsha, Hunan Province, Chin;

关键词: Borneol;    α-asarone;    puerarin;    tetramethylpyrazine;    blood–brain barrier;    adenosine receptor;   

DOI  :  10.1080/10717544.2018.1516005

来源: publisher

【 摘 要 】

Puerarin (PUE) and tetramethylpyrazine (TMP) are central nervous system (CNS) drugs used in cerebrovascular diseases. Poor brain–blood barrier (BBB) permeability limited their clinical application. Borneol and α-asarone have been proposed as an oral brain-targeting enhancer. In this study, we aimed to first evaluate the ‘orifice-opening’ effect of borneol and α-asarone, both aromatic resuscitation drugs, on improvement of brain delivery of PUE and TMP and second to investigate whether the enhancing effects were associated with adenosine receptors (ARs)-mediated trans-BBB pathway. In vitro BBB model was established and borneol and α-asarone significantly increased the cumulative amount of permeated PUE and TMP and the enhancing effects could be counteracted by AR inhibitors. Borneol and α-asarone could decrease expression of ZO-1, an important BBB junction protein, but inversely increase the expression of A1AR and A2AAR. In vivo pharmacokinetic study also confirmed that oral co-administration of borneol or α-asarone significantly increased AUCbrain for PUE and TMP. These results suggested that borneol and α-asarone are both effective adjuvant agents for delivery of PUE and TMP to the brain.

【 授权许可】

CC BY