Inhibitory effect of Iboga-type indole alkaloids on capsaicin-induced contraction in isolated mouse rectum.
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 (30-300 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 (3-100 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.
Department of Biofunctional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Mee Wah
MW
Lo
Kenjiro
K
Matsumoto
Masumi
M
Iwai
Kimihito
K
Tashima
Mariko
M
Kitajima
Syunji
S
Horie
Hiromitsu
H
Takayama
D000818:Animals; D029062:Apocynaceae / Q000737:chemistry; D002211:Capsaicin / Q000494:pharmacology*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D026121:Indole Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D012007:Rectum / Q000187:drug effects*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism
D026121:Indole Alkaloids; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D002211:Capsaicin