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.

中文翻译：

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冰片和α-细辛酮作为佐剂，通过激活腺苷受体来改善葛根素和四甲基吡嗪的血脑屏障通透性。

葛根素（PUE）和四甲基吡嗪（TMP）是用于脑血管疾病的中枢神经系统（CNS）药物。脑血屏障（BBB）通透性差限制了其临床应用。冰片和α-细辛醚已被提议作为口服脑靶向增强剂。在这项研究中，我们的目的是首先评估冰片和芳族复苏药物冰片和α-细辛对改善PUE和TMP的脑部传递的“开孔”作用，其次要研究增强作用是否与腺苷受体相关（ARs）介导的跨BBB途径。建立了体外BBB模型，冰片和α-细辛醚显着增加了渗透的PUE和TMP的累积量，增强作用可以被AR抑制剂抵消。冰片和α-细辛可以降低ZO-1的表达，一种重要的BBB连接蛋白，但反过来会增加A1AR和A2AAR的表达。体内药代动力学研究还证实，冰片或α-细辛酮的口服联合给药显着增加了PUE和TMP的AUCbrain。这些结果表明，冰片和α-细辛酮都是将PUE和TMP输送至大脑的有效佐剂。