Inhibitory effect of Iboga-type indole alkaloids on capsaicin-induced contraction in isolated mouse rectum

Abstract

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.

Nonaqueous capillary electrophoresis–mass spectrometry: A versatile, straightforward tool for the analysis of alkaloids from psychoactive plant extracts

“…The seeds and the bark of V. africana contain up to 10% iboga alkaloids and were traditionally used in West Africa as a cure for diarrhea with antiulcer properties [], as a hunting drug, stimulant, and as an aphrodisiac agent. It is also used by African “wizards” for creating visions [].…”

Evaluation of Antidiarrheal Activity of 80% Methanol Extract and Solvent Fractions of the Leaves of Withania somnifera (L.) Dunal in Swiss Albino Mice

“…Flavonoids and terpenoids showed a concentration-dependent inhibition of spontaneous muscle contractions on isolated rat ileum [ 64 ]. Alkaloids isolated from the root extract of Voacanga africana also showed inhibitory activity on contractility of intestinal muscle against capsaicin-induced contraction of muscle isolated from mouse rectum [ 65 ]. Additionally, from a previous study, withanolides, isolated from the leaves of W. somnifera, showed significant antispasmodic activity and calcium antagonism action on a spontaneously contracted jejunum isolated from the rabbit intestine [ 38 ].…”

Mass Spectrometry Imaging of the Capsaicin Localization in the Capsicum Fruits

“…Capsicum fruit is an important constituent of traditional Chinese medicine as well as spice and condiment. Many pharmacological properties of the alkaloidcapsaicin have been reported [1][2][3][4]. There are numerous reports on the effects of capsaicin on the nervous system [5], for antimicrobial [6], the polymorphism [7] and transient receptor potential vaniloid type 1(TRPV1) [8].…”