Ephedrine Alkaloids-Free Ephedra Herb Extract, EFE, Has No Adverse Effects Such as Excitation, Insomnia, and Arrhythmias

• Published in: Biological & pharmaceutical bulletin Vol. 41; no. 2; pp. 247 - 253
• Main Authors: Takemoto, Hiroaki, Takahashi, Jun, Hyuga, Sumiko, Odaguchi, Hiroshi, Uchiyama, Nahoko, Maruyama, Takuro, Yamashita, Tadatoshi, Hyuga, Masashi, Oshima, Naohiro, Amakura, Yoshiaki, Hakamatsuka, Takashi, Goda, Yukihiro, Hanawa, Toshihiko, Kobayashi, Yoshinori
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 2018; Japan Science and Technology Agency
• Subjects: adverse effect; Alkaloids; Alkaloids - analysis; Alkaloids - toxicity; Analgesics; Analgesics, Non-Narcotic - administration & dosage; Analgesics, Non-Narcotic - adverse effects; Analgesics, Non-Narcotic - chemistry; Animals; Animals, Outbred Strains; Anxiety - blood; Anxiety - chemically induced; Anxiety - etiology; Anxiety - prevention & control; Arrhythmia; Arrhythmias, Cardiac - blood; Arrhythmias, Cardiac - chemically induced; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - prevention & control; Bans; Behavior, Animal; Caffeine - poisoning; Cardiac arrhythmia; Central Nervous System Stimulants - poisoning; Dietary Supplements - adverse effects; Dietary Supplements - analysis; Electrophysiology; Ephedra; Ephedra - chemistry; Ephedra Herb; Ephedrine; Ephedrine - administration & dosage; Ephedrine - adverse effects; Ephedrine - chemistry; ephedrine alkaloid; ephedrine alkaloid-free; Epinephrine; Fibrillation; Food Contamination; Herbs; Hypnotics and Sedatives - pharmacology; Hypokalemia; Influenza; Insomnia; Japan; Locomotor activity; Male; Metastases; Mice; Open-field behavior; P waves; Pentobarbital; Pentobarbital - pharmacology; Plant Extracts - administration & dosage; Plant Extracts - adverse effects; Plant Extracts - chemistry; Plant Stems - chemistry; Potassium - blood; Side effects; Sleep disorders; Sleep Initiation and Maintenance Disorders - blood; Sleep Initiation and Maintenance Disorders - chemically induced; Sleep Initiation and Maintenance Disorders - etiology; Sleep Initiation and Maintenance Disorders - prevention & control; adverse effect; ephedrine alkaloid-free; Ephedra Herb; ephedrine alkaloid
• ISSN: 0918-6158; 1347-5215
• 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 β1 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.