a Department of Pharmacy , The Second Xiangya Hospital, Central South University , Changsha , Hunan , China.
b Institute of Clinical Pharmacy, Central South University , Changsha , Hunan , China.
Drug Deliv. 2018 Nov;25(1):1858-1864. doi: 10.1080/10717544.2018.1516005.
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 AAR and AAR. In vivo pharmacokinetic study also confirmed that oral co-administration of borneol or α-asarone significantly increased AUC 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.
葛根素（PUE）和川芎嗪（TMP）是用于脑血管疾病的中枢神经系统（CNS）药物。血脑屏障（BBB）通透性差限制了它们的临床应用。冰片和α-细辛脑已被提议作为口服脑靶向增强剂。在这项研究中，我们旨在首先评估芳香开窍药物冰片和α-细辛脑对葛根素和川芎嗪脑内传递的“开窍”作用，其次研究增强作用是否与腺苷受体（AR）介导的跨 BBB 途径有关。体外 BBB 模型建立，冰片和α-细辛脑显著增加了渗透的葛根素和川芎嗪的累积量，AR 抑制剂可拮抗增强作用。冰片和α-细辛脑可降低重要的 BBB 连接蛋白 ZO-1 的表达，但相反增加了 AAR 和 AAR 的表达。体内药代动力学研究也证实，口服给予冰片或α-细辛脑可显著增加 PUE 和 TMP 的 AUC。这些结果表明，冰片和α-细辛脑都是将 PUE 和 TMP 递送到大脑的有效辅助剂。
