Discovery of indole alkaloids with cannabinoid CB1 receptor antagonistic activity.

Three indole alkaloids, voacamine (1), 3,6-oxidovoacangine (2), and a new alkaloid, 5-hydroxy-3,6-oxidovoacangine (3), isolated from Voacanga africana were found to exhibit potent cannabinoid CB1 receptor antagonistic activity. This is the first example of CB1 antagonists derived from natural alkaloids.

Asymmetric total synthesis of an iboga-type indole alkaloid, voacangalactone, newly isolated from Voacanga africana.

A new hexacyclic iboga-type indole alkaloid, voacangalactone (1), was isolated from Voacanga africana , and its structure including the absolute configuration was established by asymmetric total synthesis involving such key steps as the asymmetric Diels-Alder reaction using an aminodiene and the construction of an isoquinuclidine ring and an indole skeleton.

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.

Influences of properties of protein and adsorption surface on removal kinetics of protein adsorbed on metal surface by H2O2-electrolysis treatment.

"H(2)O(2)-electrolysis" treatment is an alternative method for removing proteinaceous materials that are adsorbed to metal surfaces. The method is based on the generation of hydroxyl radicals by electrolysis of hydrogen peroxide and the subsequent decomposition of organic substances adhering to the metal surface. We herein investigated the influence of some parameters on the kinetics of protein removal by H(2)O(2)-electrolysis. These parameters included the properties of proteins and the type of metal surface. Sixteen types of proteins and nine types of metal surfaces were used. The removal of adsorbed protein from a metal surface during the treatment was monitored by ellipsometry. Apparent first-order rate constants for removal, k(c)(l), for various adsorption and treatment conditions were determined. The k(c)(l) value varied markedly with the type of protein and was also influenced by the pH used in the adsorption. The isoelectric point (pI) of protein used was found to be a major factor. The amount of adsorbed protein removed by a unit amount of (·)OH was larger for a metal surface with a lower pI. The impact of the properties of the protein and metal surface on the removal kinetics are discussed, focusing on relationships with the adsorption characteristics of the protein.

Embolic attack in patients with atrial fibrillation and atrial thrombus depends on the character of the thrombus.

It is very important to prevent embolisms from left atrial thrombi (LAT). The present study was a trial for the management of patients with AT using 122 patients with atrial fibrillation and LAT who were followed for 1 year after transesophageal echocardiography. LAT were classified by their shape and mobility into the mobile ball type (MB, n=28), fixed ball type (FB, n=32) and mountain type (MO, n=42). The patients were given warfarin (INR: 1.5-2.0, n=43), aspirin 81 mg (n=74) and/or ticlopidine 200 mg/day (n=31). The embolic rate (ER) in the MB group was significantly higher than in the other groups [ie, MB 39.3% vs FB 15.6% (p<0.05), vs MO 2.4% (p<0.05)]. The ER in the FB group was significantly higher than in the MO group (p<0.05). Therapy with a combination of ticlopidine and aspirin reduced the ER in the patients with ball thrombi. The ER of the ball thrombus type group, especially the MB group, was very high in spite of therapy with anti-coagulants and/or anti-platelet agents, and such patients should be treated by early surgical intervention. However, the combination of ticlopidine and aspirin may be useful for preventing embolism.