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 typ...

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Veröffentlicht in:Journal of natural medicines 2011-01, Vol.65 (1), p.157-165
Hauptverfasser: Lo, Mee Wah, Matsumoto, Kenjiro, Iwai, Masumi, Tashima, Kimihito, Kitajima, Mariko, Horie, Syunji, Takayama, Hiromitsu
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container_issue 1
container_start_page 157
container_title Journal of natural medicines
container_volume 65
creator Lo, Mee Wah
Matsumoto, Kenjiro
Iwai, Masumi
Tashima, Kimihito
Kitajima, Mariko
Horie, Syunji
Takayama, Hiromitsu
description 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 .
doi_str_mv 10.1007/s11418-010-0478-6
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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. 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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. 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inhibitors</topic><topic>TRPV Cation Channels - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lo, Mee Wah</creatorcontrib><creatorcontrib>Matsumoto, Kenjiro</creatorcontrib><creatorcontrib>Iwai, Masumi</creatorcontrib><creatorcontrib>Tashima, Kimihito</creatorcontrib><creatorcontrib>Kitajima, Mariko</creatorcontrib><creatorcontrib>Horie, Syunji</creatorcontrib><creatorcontrib>Takayama, Hiromitsu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of natural medicines</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lo, Mee Wah</au><au>Matsumoto, Kenjiro</au><au>Iwai, Masumi</au><au>Tashima, Kimihito</au><au>Kitajima, Mariko</au><au>Horie, Syunji</au><au>Takayama, Hiromitsu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibitory effect of Iboga-type indole alkaloids on capsaicin-induced contraction in isolated mouse rectum</atitle><jtitle>Journal of natural medicines</jtitle><stitle>J Nat Med</stitle><addtitle>J Nat Med</addtitle><date>2011-01-01</date><risdate>2011</risdate><volume>65</volume><issue>1</issue><spage>157</spage><epage>165</epage><pages>157-165</pages><issn>1340-3443</issn><eissn>1861-0293</eissn><abstract>Voacanga africana (Apocynaceae) is used as an anti-diarrheal medicine in West Africa. 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subjects Animals
Apocynaceae - chemistry
Biomedical and Life Sciences
Biomedicine
Capsaicin - pharmacology
Complementary & Alternative Medicine
Immunohistochemistry
In Vitro Techniques
Indole Alkaloids - chemistry
Indole Alkaloids - pharmacology
Medicinal Chemistry
Mice
Muscle Contraction - drug effects
Muscle, Smooth - drug effects
Original Paper
Pharmacology/Toxicology
Pharmacy
Plant Sciences
Rectum - drug effects
TRPV Cation Channels - antagonists & inhibitors
TRPV Cation Channels - metabolism
title Inhibitory effect of Iboga-type indole alkaloids on capsaicin-induced contraction in isolated mouse rectum
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