Department of Radiopharmaceuticals Development, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
Phytomedicine. 2018 Jan 1;38:84-89. doi: 10.1016/j.phymed.2017.05.006. Epub 2017 May 26.
Apocynin is a constituent of the medicinal herb Picrorhiza kurroa. It is an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase. This compound shows potential anti-inflammatory and antioxidant effects and has been tested as a neuroprotectant in many animal models of brain disease. In such studies, understanding the brain kinetics of apocynin would be important for interpreting its in vivo efficacy; however, little has been reported on the kinetics of apocynin in the brain.
The purpose of this study is to investigate the kinetics and metabolism of apocynin in the brain of mice.
The kinetics and metabolism of apocynin were examined using [C]apocynin and positron-emission tomography (PET).
In vivo PET scanning was performed in mice for 20min after intraperitoneal administration of an apocynin solution containing [C]apocynin. Metabolites in the brain were analyzed using high-performance liquid chromatography. The doses of apocynin used ranged from <1.5 µg/kg (tracer dose) to 100mg/kg.
Brain radioactivity during the period of 0 to 20min after administration was negligible at the tracer dose and extremely low at the dose of 10mg/kg. Moderate radioactivity was observed in the brain a few minutes after administration at the doses of 25 and 50mg/kg and rapidly decreased thereafter. At a dose of 100mg/kg, [C]apocynin resulted in a high uptake of radioactivity followed by a gradual washout. In contrast to the brain, a clear dose-dependent increase in radioactivity was not observed in the blood. The fraction of the unchanged form in the brain decreased with time, and the degree of the reduction depended on apocynin doses: apocynin was rapidly metabolized in the brain at lower doses, whereas it was slowly decomposed at higher doses. On the basis of these data, the maximum apocynin concentrations in the brain were calculated to be 10 µM (10mg/kg), 49 µM (25mg/kg), 150 µM (50mg/kg), and 380 µM (100mg/kg). A metabolite observed in the brain was found to be apocynin glucuronide but not diapocynin, an active metabolite.
These results would be useful for an evaluation of the potential efficacy of apocynin as a neuroprotective agent.
钩吻素子是一种药用植物胡黄连中的成分。它是烟酰胺腺嘌呤二核苷酸磷酸氧化酶的抑制剂。这种化合物具有潜在的抗炎和抗氧化作用，并已在许多脑部疾病的动物模型中被测试为神经保护剂。在这些研究中，了解钩吻素子在大脑中的动力学对于解释其体内疗效非常重要；然而，关于钩吻素子在大脑中的动力学的研究却很少。
本研究旨在研究钩吻素子在小鼠大脑中的动力学和代谢。
使用 [C]钩吻素子和正电子发射断层扫描（PET）研究了钩吻素子的动力学和代谢。
在腹腔注射含有 [C]钩吻素子的钩吻素子溶液后 20 分钟内，对小鼠进行体内 PET 扫描。使用高效液相色谱法分析脑内代谢物。使用的钩吻素子剂量范围从 <1.5µg/kg（示踪剂量）到 100mg/kg。
在给药后 0 至 20 分钟期间，脑放射性在示踪剂量时可忽略不计，在 10mg/kg 时极低。在 25 和 50mg/kg 的剂量下，给药后几分钟内观察到中度放射性，随后迅速下降。在 100mg/kg 时，[C]钩吻素子导致放射性摄取增加，随后逐渐清除。与大脑相比，在血液中没有观察到与剂量呈依赖性的放射性增加。脑内未改变形式的分数随时间减少，减少的程度取决于钩吻素子的剂量：在较低剂量下，钩吻素子在大脑中迅速代谢，而在较高剂量下则缓慢分解。基于这些数据，计算出大脑中最大的钩吻素子浓度分别为 10µM（10mg/kg）、49µM（25mg/kg）、150µM（50mg/kg）和 380µM（100mg/kg）。在大脑中观察到的一种代谢物被发现是钩吻素子葡萄糖醛酸苷，但不是活性代谢物二钩吻素子。
这些结果对于评估钩吻素子作为神经保护剂的潜在疗效将是有用的。
