Department of Pharmacognosy, School of Pharmacy, Kitasato University, Tokyo, Japan; Oriental Medicine Research Center of Kitasato University, Tokyo, Japan.
Oriental Medicine Research Center of Kitasato University, Tokyo, Japan.
J Ethnopharmacol. 2023 Jan 30;301:115827. doi: 10.1016/j.jep.2022.115827. Epub 2022 Oct 11.
In our previous study, we reported that Ephedra Herb extract (EHE) increased the locomotor activity of mice in the open-field test and reduced the immobility time in the forced swim test. Ephedrine alkaloids (EAs) are thought to be responsible for the adverse effects of Ephedra Herb. However, there are no reports to verify that the adverse effects of Ephedra Herb are caused by the amount of EAs in the herb. Therefore, we investigated whether these adverse effects of EHE are caused by the amounts of ephedrine (Eph) and pseudoephedrine (Pse) in the herbal extract. In a preliminary study of the time course analysis of the open field test, we newly observed that EHE evoked switching from transient sedation to sustained excitement.
We aimed to confirm whether EHE evokes switching from transient sedation to sustained excitement, investigate whether these actions of EHE are caused by the amount of ephedrine (Eph) and pseudoephedrine (Pse) in the herbal extract, and clarify the molecular mechanism of the transient sedative effect.
The locomotor activity of mice was tested using the open-field test. The immobility times were measured using a forced swim test, and the motor dysfunction in mice was tested using the rotarod test.
EHE, Eph, and Pse induced transient motionlessness between 0 and 15 min after oral administration, however, they did not induce depression-like behavior and motor dysfunction in mice, suggesting that the motionlessness induced by EHE, Eph, or Pse resulted from sedation. The α2a adrenoceptor inhibitor, atipamezole, decreased their sedative effects. Thus, immediately after EHE administration, the transient sedative effect is mediated through the activation of the α2a adrenoreceptor by Eph and Pse. EHE and Eph increased total locomotor activity for 15-120 min after oral administration; however, Pse had no effect. Therefore, the slow-onset and sustained excitatory effects of EHE are mediated by Eph.
We discovered for the first time that EHE evokes diphasic action by switching from transient sedation to sustained excitement. The transient sedation was evoked by the Eph and Pse in the herbal extract via activation of the α2a adrenoceptor and the sustained excitement was caused by the Eph in the herbal extract.
在我们之前的研究中，我们报告说麻黄草提取物（EHE）增加了旷场试验中小鼠的活动，减少了强迫游泳试验中小鼠的不动时间。麻黄生物碱（EAs）被认为是麻黄草产生不良反应的原因。然而，没有报道证实麻黄草的不良反应是由草药中 EAs 的含量引起的。因此，我们研究了 EHE 的这些不良反应是否是由草药提取物中麻黄碱（Eph）和伪麻黄碱（Pse）的含量引起的。在旷场试验时间过程分析的初步研究中，我们新观察到 EHE 引起从短暂镇静到持续兴奋的转变。
我们旨在证实 EHE 是否引起从短暂镇静到持续兴奋的转变，研究 EHE 的这些作用是否是由草药提取物中麻黄碱（Eph）和伪麻黄碱（Pse）的含量引起的，并阐明短暂镇静作用的分子机制。
使用旷场试验测试小鼠的运动活动。使用强迫游泳试验测量不动时间，使用旋转棒试验测试小鼠的运动功能障碍。
EHE、Eph 和 Pse 在口服后 0 至 15 分钟内诱导短暂的静止，然而，它们不会在小鼠中诱导抑郁样行为和运动功能障碍，表明 EHE、Eph 或 Pse 诱导的静止是由镇静作用引起的。α2a 肾上腺素受体抑制剂阿替美唑降低了它们的镇静作用。因此，EHE 给药后立即，Eph 和 Pse 通过激活α2a 肾上腺素受体产生短暂的镇静作用。EHE 和 Eph 在口服后 15-120 分钟内增加了总运动活动；然而，Pse 没有作用。因此，EHE 和 Eph 的缓慢发作和持续兴奋作用是由 Eph 介导的。
我们首次发现 EHE 通过从短暂镇静到持续兴奋的转换引起双相作用。草药提取物中的 Eph 和 Pse 通过激活α2a 肾上腺素受体引起短暂镇静，而草药提取物中的 Eph 引起持续兴奋。
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