title: Ephedra Herb extract activates/desensitizes transient receptor potential vanilloid 1 and reduces capsaicin-induced pain.
abstract: Kampo medicines containing Ephedra Herb (EH) such as eppikajutsubuto and makyoyokukanto are used to treat myalgia, arthralgia, and rheumatism. The analgesic effects of these Kampo medicines are attributed to the anti-inflammatory action of EH. However, the molecular mechanism of the analgesic effect of EH remains to be clarified. In this study, the effects of EH extract (EHE) on transient receptor potential vanilloid 1 (TRPV1), a nonselective ligand-gated cation channel, which plays an essential role in nociception on sensory neurons, were investigated using mTRPV1/Flp-In293 cells (stable mouse TRPV1-expressing transfectants). Administration of EHE increased the intracellular Ca2+concentration in these cells, which was inhibited by the TRPV1 antagonist, N-(4-tert-butylphenyl)-1,2-dihydro-4-(3-chloropyridine-2-yl) tetrahydropyrazine-1-carboxamide (BCTC), indicating that EHE activated TRPV1. Examination of EHE-induced nociceptive pain in vivo revealed that an intradermal (i.d.) injection of EHE into the hind paw of mice induced paw licking, a pain-related behavior, and that the extract increased paw licking times in a dose-dependent manner. The EHE-induced paw licking was also inhibited by BCTC. An i.d. injection of EHE 30 min before administration of capsaicin decreased capsaicin-induced paw licking times. Similarly, oral administration of the extract also suppressed capsaicin-induced paw licking, without affecting the physical performance of the mice. These results suggest that EHE suppresses capsaicin-induced paw licking by regulating TRPV1 activity. Thus, the antinociceptive effects of EHE seem to be produced by its direct action on sensory neurons through TRPV1.
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.|Oriental Medicine Research Center, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Nakamori
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.|Oriental Medicine Research Center, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Takahashi
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.identifier: http://orcid.org/0000-0001-7612-2870
authors.initials: S
authors.lastname: Hyuga
authors.affiliation: Department of Biochemical Toxicology, Yokohama University of Pharmacy, 601 Matano-cho, Totsuka-ku, Yokohama, 245-0066, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka-Kagawa
authors.affiliation: Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya, 468-8503, Japan.
authors.forename: Hideto
authors.initials: H
authors.lastname: Jinno
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: 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
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.|Oriental Medicine Research Center, Kitasato University, 5-9-1, Shirokane, Minato-ku, Tokyo, 108-8642, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002211:Capsaicin / Q000009:adverse effects*; D029789:Ephedra / Q000737:chemistry*; D006801:Humans; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced*; D010147:Pain Measurement; D050916:TRPV Cation Channels; D014162:Transfection
chemical_list: D000893:Anti-Inflammatory Agents; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D002211:Capsaicin
keywords: Analgesia; Capsaicin; Ephedra Herb; Nociception; Pain; TRPV1