Ephedrine Alkaloids-Free Ephedra Herb Extract, EFE, Has No Adverse Effects Such as Excitation, Insomnia, and Arrhythmias
Ephedrine Alkaloids-Free Ephedra Herb Extract, EFE, Has No Adverse Effects Such as Excitation, Insomnia, and Arrhythmias
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DOI：
10.1248/bpb.b17-00803
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发表时间：
2018-02-01
影响因子：
2
通讯作者：
Kobayashi, Yoshinori
中科院分区：
文献类型：
--
作者：
Takemoto, Hiroaki;Takahashi, Jun;Kobayashi, Yoshinori
无麻黄碱麻黄提取物（EFE）已被开发用于消除麻黄碱诱导的交感神经过度激活所引起的不良反应。以前，我们报道，EFE具有镇痛，抗流感，和癌症转移抑制作用的水平相当的麻黄草药提取物（EHE）。然而，尚未证明EFE没有EHE的已知副作用，如兴奋，失眠和心律失常。在这项研究中，这些不良反应的发生率进行了比较之间的小鼠管理EHE和那些管理EFE。与溶剂处理小鼠中的相应值相比，在EHE处理小鼠中观察到旷场试验中运动活性增加、强迫游泳试验中不动时间减少和戊巴比妥诱导睡眠试验中睡眠时间减少。相反，EFE在这些测试中没有明显的效果。在心电图中，心房颤动（即，心律不规则、P波缺失和f波出现）。提示心房颤动是由肾上腺素PI受体刺激引起的，而不是由低钾血症引起的。然而，EFE不影响心脏电生理。这些结果表明，上述副作用是由EHE中的麻黄碱生物碱引起的，而EFE没有这些不良反应，如兴奋，失眠和心律失常。因此，EFE是一种很有前途的新植物药，副作用少。
Ephedrine alkaloids-free Ephedra Herb extract (EFE) has been developed to eliminate the adverse effects caused by ephedrine alkaloid-induced sympathetic hyperactivation. Previously, we reported that EFE possesses analgesic, anti-influenza, and cancer metastatic inhibitory effects at comparable levels to that of Ephedra Herb extract (EHE). However, it has not yet been demonstrated that EFE is free from the known side effects of EHE, such as excitation, insomnia, and arrhythmias. In this study, the incidence of these adverse effects was compared between mice administered EHE and those administered EFE. Increased locomotor activity in an open-field test, reduced immobility times in a forced swim test, and reduced sleep times in a pentobarbital-induced sleep test were observed in EHE-treated mice, when compared to the corresponding values in vehicle-treated mice. In contrast, EFE had no obvious effects in these tests. In electrocardiograms, atrial fibrillation (i.e., irregular heart rhythm, absence of P waves, and appearance of f waves) was observed in the EHE-treated mice. It was suggested that this atrial fibrillation was induced by stimulation of adrenaline PI receptors, but not by hypokalemia. However, EFE did not affect cardiac electrophysiology. These results suggest that the abovementioned side effects are caused by ephedrine alkaloids in EHE, and that EFE is free from these adverse effects, such as excitation, insomnia, and arrhythmias. Thus, EFE is a promising new botanical drug with few adverse effects.