The First Affiliated Hospital of Henan University of Chinese Medicine, Renmin road no.19, Jinshui District, Zhengzhou City, 450000, Henan Province, China.
Nanjing University of Chinese Medicine, Xianlin road no.138, Qixia District, Nanjing City, Jiangsu Province, 210023, China.
Mol Brain. 2019 Feb 8;12(1):11. doi: 10.1186/s13041-019-0428-5.
We aimed to test the therapeutic effects of baicalin on attention deficit hyperactivity disorder (ADHD) in an animal model and to explain the potential mechanism. We investigated the therapeutic effects and mechanisms of baicalin in a spontaneously hypertensive rat (SHR) model of ADHD depending on the dopamine (DA) deficit theory. In this study, fifty SHRs were randomly divided into five groups: methylphenidate (MPH), baicalin (50 mg/kg, 100 mg/kg, or 150 mg/kg), and saline-treated. Ten Wistar Kyoto (WKY) rats were used as controls. All rats were orally administered the treatment for four weeks. Motor activity, spatial learning and memory ability were assessed with the open-field and Morris water-maze tests. The mRNA and protein levels of tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2), synaptosomal-associated protein of molecular mass 25kD (SNAP25) and synataxin 1a in synaptosomes were detected with real-time polymerase chain reaction (PCR) and Western blot. In addition, DA levels were measured in the prefrontal cortex and striatum. The results indicated that both MPH and baicalin at doses of 150 mg/kg and 100 mg/kg significantly decreased the hyperactivity and improved the spatial learning memory deficit in the SHRs and increased the synaptosomal mRNA and protein levels of TH, SNAP25, VMAT2 and synataxin 1a compared with saline treatment. MPH significantly increased DA levels in both the prefrontal cortex (PFC) and striatum, while baicalin significantly increased DA levels only in the striatum. The results of the present study showed that baicalin treatment was effective for controlling the core symptoms of ADHD. Baicalin increased DA levels only in the striatum, which suggested that baicalin may target the striatum. The increased DA levels may partially be attributed to the increased mRNA and protein expression of TH, SNAP25, VMAT2, and syntaxin 1a. Therefore, these results suggested that the pharmacological effects of baicalin were associated with the synthesis, vesicular localization, and release of DA and might be effective in treating ADHD. However, further studies are required to better understand the molecular mechanisms underlying these findings.
根据多巴胺（DA）缺乏理论，探讨黄芩苷对注意缺陷多动障碍（ADHD）动物模型的治疗作用及其潜在机制。
采用自发性高血压大鼠（SHR）ADHD 模型，观察黄芩苷的治疗作用及其机制。
50 只 SHR 随机分为 5 组，即：哌甲酯（MPH）组、黄芩苷（50、100、150 mg/kg）组和生理盐水组，另设 10 只 Wistar Kyoto（WKY）大鼠为对照组。所有大鼠连续灌胃给药 4 周。采用旷场和 Morris 水迷宫实验评价大鼠的运动活性和空间学习记忆能力；实时聚合酶链反应（PCR）和 Western blot 检测大鼠海马突触体中酪氨酸羟化酶（TH）、囊泡单胺转运体 2（VMAT2）、突触相关蛋白 25kD（SNAP25）和突触融合蛋白 1a（syntaxin 1a）mRNA 和蛋白的表达水平；采用高效液相色谱电化学法检测大鼠前额叶皮质和纹状体 DA 含量。结果显示，黄芩苷高、中剂量（150、100 mg/kg）和 MPH 均可显著降低 SHR 的多动行为，改善其空间学习记忆障碍，且能上调突触体 TH、SNAP25、VMAT2 和 syntaxin 1a mRNA 和蛋白的表达水平，与生理盐水组比较差异均有统计学意义（P<0.05）。MPH 能显著升高 SHR 前额叶皮质和纹状体 DA 含量，而黄芩苷仅能显著升高 SHR 纹状体 DA 含量。黄芩苷治疗能改善 ADHD 核心症状，可能与增加 DA 含量有关，而增加 DA 含量可能与上调 TH、SNAP25、VMAT2 和 syntaxin 1a 的表达有关。结论：黄芩苷可能通过增加突触体 DA 的合成、囊泡摄取和释放发挥治疗 ADHD 的作用。
