title: Ephedrine alkaloids-free Ephedra Herb extract: a safer alternative to ephedra with comparable analgesic, anticancer, and anti-influenza activities.
abstract: It is generally accepted that the primary pharmacological activities and adverse effects of Ephedra Herb are caused by ephedrine alkaloids. Interestingly, our research shows that Ephedra Herb also has ephedrine alkaloid-independent pharmacological actions, such as c-MET inhibitory activity. This study describes the preparation of an ephedrine alkaloids-free Ephedra Herb extract (EFE) by ion-exchange column chromatography, as well as in vitro and in vivo evaluation of its pharmacological actions and toxicity. We confirmed that EFE suppressed hepatocyte growth factor (HGF)-induced cancer cell motility by preventing both HGF-induced phosphorylation of c-Met and its tyrosine kinase activity. We also investigated the analgesic effect of EFE. Although the analgesic effect of Ephedra Herb has traditionally been attributed to pseudoephedrine, oral administration of EFE reduced formalin-induced pain in a dose-dependent manner in mice. Furthermore, we confirmed the anti-influenza virus activity of EFE by showing inhibition of MDCK cell infection in a concentration-dependent manner. All assessments of toxicity, even after repeated oral administration, suggest that EFE would be a safer alternative to Ephedra Herb. The findings described here suggest that EFE has c-Met inhibitory action, analgesic effect, and anti-influenza activity, and that it is safer than Ephedra Herb extract itself. Therefore, EFE could be a useful pharmacological agent.
authors.affiliation: Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan. hyuga-s@insti.kitasato-u.ac.jp.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Hyuga
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Hyuga
authors.affiliation: Department of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1, Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Oshima
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Maruyama
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamakura
authors.affiliation: TOKIWA Phytochemical CO., Ltd., 158 Kinoko, Sakura-shi, Chiba, 285-0801, Japan.
authors.forename: Tadatoshi
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime, 790-8578, Japan.
authors.forename: Morio
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Department of Pharmacognosy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime, 790-8578, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Amakura
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hakamatsuka
authors.affiliation: Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Odaguchi
authors.affiliation: National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Goda
authors.affiliation: Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hanawa
mesh_terms: D000470:Alkaloids / Q000737:chemistry; D000700:Analgesics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D029789:Ephedra / Q000737:chemistry*; D004809:Ephedrine / Q000032:analysis / Q000737:chemistry*; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy*
chemical_list: D000470:Alkaloids; D000700:Analgesics; D000970:Antineoplastic Agents; D004809:Ephedrine
keywords: Analgesia; EFE; Ephedra Herb; Influenza; Kampo; c-Met