Department of Pharmacognosy, School of Pharmacy, Kitasato University.
Oriental Medicine Research Center of Kitasato University.
Biol Pharm Bull. 2018;41(2):247-253. doi: 10.1248/bpb.b17-00803.
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 β 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.
无麻黄碱的麻黄草药提取物（EFE）已被开发出来，以消除麻黄碱引起的交感神经兴奋过度所导致的不良反应。此前，我们报道过 EFE 具有与麻黄草药提取物（EHE）相当的镇痛、抗流感和抑制癌症转移的作用。然而，尚未证明 EFE 没有 EHE 已知的副作用，如兴奋、失眠和心律失常。在这项研究中，比较了给予 EHE 和 EFE 的小鼠中这些不良反应的发生率。与对照组相比，EHE 处理的小鼠在旷场试验中表现出更高的运动活性，在强迫游泳试验中减少了不动时间，在戊巴比妥诱导的睡眠试验中减少了睡眠时间。相比之下，EFE 在这些测试中没有明显的作用。在心电图中，EHE 处理的小鼠出现了心房颤动（即不规则的心律、无 P 波和出现 f 波）。据推测，这种心房颤动是由肾上腺素β受体的刺激引起的，而不是由低钾血症引起的。然而，EFE 并不影响心脏电生理。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 是一种具有较少不良反应的有前途的新型植物药。
