Search

Bauhinia malabarica Roxb. has been used in Thai traditional medicine for wound healing, as a diuretic, to fight dysentery and as an emmenagogue. Seven flavonols, including 6,8-di-C-methylkaempferol 3-methyl ether, kaempferol, afzelin, quercetin, isoquercitrin, quercitrin, and hyperoside were isolated from the methanol extract of leaves.

[reaction: see text] New types of four gelsenicine-related oxindole alkaloids were isolated from the leaves of Gelsemium elegans Benth. Gelsedilam (1) and 14-acetoxygelsedilam (2) are the first examples of 18,19-nor-type monoterpenoid indole alkaloids. Gelsefuranidine (3) and gelseiridone (4) have, respectively, an additional furan residue or an iridoid unit on the gelsenicine-related monoterpenoid indole alkaloid.

The effect of an indole-alkaloid mitragynine isolated from the Thai medicinal herb kratom (Mitragyna speciosa) on neurogenic contraction of smooth muscle was studied in guinea-pig vas deferens. Mitragynine inhibited the contraction of the vas deferens produced by electrical transmural stimulation. On the other hand, mitragynine failed to affect the responses to norepinephrine and ATP. Mitragynine did not reduce KCl-induced contraction in the presence of tetrodotoxin, prazosin and alpha,beta-methylene ATP. Mitragynine inhibited nicotine- or tyramine-induced contraction. By using the patch-clamp technique, mitragynine was found to block T- and L-type Ca2+ channel currents in N1E-115 neuroblastoma cells. In the Ca2+ measurement by a fluorescent dye method, mitragynine reduced KCl-induced Ca2+ influx in neuroblastoma cells. The present results suggest that mitragynine inhibits the vas deferens contraction elicited by nerve stimulation, probably through its blockade of neuronal Ca2+ channels.

Recently, we found that mitragynine, a major constituent of Mitragyna speciosa, has an opioid agonistic activity, but its weak potency could not explain the opium-like effect of this plant. In the present study, bioassay-guided fractionation of the crude extract of the leaves of M. speciosa was carried out to search for potent opioid agonists other than mitragynine. Opioid agonistic activities were evaluated using twitch contraction induced by electrical stimulation in guinea-pig ileum. The crude extract of M. speciosa inhibited the twitch contraction in a concentration-dependent manner. The inhibition was reversed by naloxone. The opioid effect was detected only in the crude base fraction, which was followed by the isolation of five indole alkaloids. Among these alkaloids, 7-hydroxymitragynine showed the most potent opioid effect on the electrically-stimulated contraction (pD (2) = 8.38 +/- 0.12). The potency, calculated using pD (2) values, was 30- and 17-fold higher than that of mitragynine and morphine, respectively. Antagonism of naloxone on concentration-response curves for 7-hydroxymitragynine confirmed its opioid effect. These results suggest that the opioid effect of M. speciosa is mostly based on the activity of 7-hydroxymitragynine.

Three monoterpenoid gluco-indole alkaloids, 3beta-isodihydrocadambine, cadambine, and 3alpha-dihydrocadambine, were isolated from Nauclea cadamba ROXB. growing in Thailand. The stereochemistry at C19 in 3beta-isodihydrocadambine was elucidated to be R by spectroscopic analysis. Treatment of 3alpha-dihydrocadambine with beta-glucosidase in aqueous ammonium acetate solution gave an indolopyridine alkaloid, 16-carbomethoxynaufoline, and an unusually rearranged compound.

Two new biflavonoids, namely, 6'"-hydroxylophirone B (1) and 6'"-hydroxylophirone B 4"'-O-beta-glucoside (2), were isolated from the stem bark of Ochna integerrima, together with five known compounds. The structures of 1 and 2 were determined by spectral data interpretation.

Mitragynine, an indole alkaloid from Thai folk medicine Mitragyna speciosa, exerts agonistic effects on opioid receptors. Gastric acid secretion is proposed to be regulated by opioid receptors in the central nervous system (CNS). Previously, we reported the dual roles (inhibition via micro-opioid receptors and stimulation via kappa-opioid receptors) of the opioid system in the central control of gastric acid secretion. We investigated whether mitragynine affects gastric acid secretion via opioid receptors in the CNS. Injection of mitragynine (30 microg) alone into the lateral cerebroventricle did not have a significant effect on basal gastric acid secretion in the perfused stomach of anesthetized rats. Injection of mitragynine (3-30 microg) into the fourth cerebroventricle, like morphine, inhibited 2-deoxy-D-glucose-stimulated gastric acid secretion. The inhibitory effect of mitragynine (30 microg) was reversed by naloxone (100 microg). These results suggest that mitragynine has a morphine-like action on gastric acid secretion in the CNS.

We have previously elucidated the opiate-like action of mitragynine, an active principle isolated from the Thai medicinal plant Mitragyna speciosa. In the present study, effects of the related compound, mitragynine pseudoindoxyl on electrically stimulated contraction in guinea pig ileum and mouse vas deferens, and on its binding affinity in the guinea pig brain membranes were studied. Mitragynine pseudoindoxyl inhibited the electrically stimulated ileum and mouse vas deferens contractions in a concentration-dependent manner. In the ileum, the effective concentration is in an nM order, being nearly equivalent to reported concentrations of the micro-opioid receptor agonist [D-Ala2, Met-Phe4, Gly-ol5] enkephalin (DAMGO), and is 100- and 20-fold smaller than those of mitragynine and morphine, respectively. In the vas deferens, it is 35-fold smaller than that of morphine. The inhibitory action of mitragynine pseudoindoxyl in the ileum was antagonized by the non-selective opioid receptor antagonist naloxone and the micro-receptor antagonist naloxonazine. It was also antagonized by the delta-receptor antagonist naltrindole in the vas deferens. Mitragynine pseudoindoxyl showed a similar binding affinity to DAMGO and naltrindole at micro- and delta-receptors, respectively. However, the affinity at kappa-receptors was negligible. The present study demonstrates that mitragynine pseudoindoxyl, a novel alkaloid structurally different from other opioid agonists, acts on opioid receptors, leading to a potent inhibition of electrically stimulated contraction in the ileum through the micro-receptors and in mouse vas deferens through delta-receptors.