Inhibitory effect of Iboga-type indole alkaloids on capsaicin-induced contraction in isolated mouse rectum
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  • 作者:Mee Wah Lo (1) (2)
    Kenjiro Matsumoto (2)
    Masumi Iwai (1)
    Kimihito Tashima (2)
    Mariko Kitajima (1)
    Syunji Horie (2)
    Hiromitsu Takayama (1)
  • 关键词:Apocynaceae ; TRPV1 ; Iboga alkaloid ; Voacangine ; Colon ; Diarrhea
  • 刊名:Journal of Natural Medicines
  • 出版年:2011
  • 出版时间:January 2011
  • 年:2011
  • 卷:65
  • 期:1
  • 页码:157-165
  • 全文大小:366KB
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  • 作者单位:Mee Wah Lo (1) (2)
    Kenjiro Matsumoto (2)
    Masumi Iwai (1)
    Kimihito Tashima (2)
    Mariko Kitajima (1)
    Syunji Horie (2)
    Hiromitsu Takayama (1)

    1. Department of Biofunctional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba, 263-8522, Japan
    2. Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo Togane, Chiba, 283-8555, Japan
  • ISSN:1861-0293
文摘
Voacanga africana (Apocynaceae) is used as an anti-diarrheal medicine in West Africa. In the present study, we investigated the effect of an extract of V. africana and its constituents on smooth muscle contraction induced by capsaicin in mouse rectum, where transient receptor potential vanilloid type 1 (TRPV1)-immunoreactive fibers are abundant. Methanol and alkaloid extracts of the root bark of V. africana were found to inhibit capsaicin-induced contraction in a dose-dependent manner (30-00?μg/ml). Major constituents isolated from the alkaloid extract were then studied for their effects on the capsaicin-induced contraction. The main active constituents were found to be Iboga-type alkaloids, including voacangine (1), 3-oxovoacangine (2), voacristine (3), and (7α)-voacangine hydroxyindolenine (4). The voacangine concentration dependently (3-00?μM) inhibited the capsaicin-induced contraction. The capsaicin-induced contraction was almost completely inhibited by the TRPV1 antagonist, N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carbox-amide (BCTC). On the other hand, the Iboga-type alkaloids did not inhibit the contractions induced by 3?μM acetylcholine and 300?μM nicotine. These results suggest that Iboga-type alkaloids isolated from V. africana inhibit capsaicin-induced contraction in the mouse rectum, possibly via the inhibition of a TRPV1-mediated pathway. This inhibition may be involved in the anti-diarrheal effect of V. africana.

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