The pharmacological interaction of compounds in ayahuasca: a systematic review

Ayahuasca is a South American psychoactive plant brew used as traditional medicine in spiritual and in cultural rituals. This is a review of the current understanding about the pharmacological mechanisms that may be interacting in ayahuasca. Searches were performed using PubMed, PsycINFO, and Web of Science databases and 16 papers were selected. As hypothesized, the primary narrative in existing research revolved around prevention of deamination of N,N-dimethyltryptamine (N,N-DMT, also referred to as DMT) by monoamine oxidase inhibitors (MAOIs) in ayahuasca. Two of the constituents, DMT and harmine, have been studied more than the secondary harmala alkaloids. At present, it is unclear whether the pharmacological interactions in ayahuasca act synergistically or additively to produce psychoactive drug effects. The included studies suggest that our current understanding of the preparation's synergistic mechanisms is limited and that more complex processes may be involved; there is not yet enough data to determine any potential synergistic interaction between the known compounds in ayahuasca. Our pharmacological understanding of its compounds must be increased to avoid the potential risks of ayahuasca use.

Xanthoangelol and 4-Hydroxyderricin Are the Major Active Principles of the Inhibitory Activities against Monoamine Oxidases on Angelica keiskei K

Monoamine oxidase inhibitors (MAOI) have been widely used as antidepressants. Recently, there has been renewed interest in MAO inhibitors. The activity-guided fractionation of extracts from Angelica keiskei Koidzumi (A. keiskei K.) led to the isolation of two prenylated chalcones, xanthoangelol and 4-hydroxyderricin and a flavonoid, cynaroside. These three isolated compounds are the major active ingredients of A. keiskei K. to inhibit the MAOs and DBH activities. Xanthoangelol is a nonselective MAO inhibitor, and a potent dopamine beta-hydroxylase (DBH) inhibitor. IC50 values of xanthoangelol to MAO-A and MAO-B were calculated to be 43.4 microM, and 43.9 microM. These values were very similar to iproniazid, which is a nonselective MAO inhibitor used as a drug against depression. The IC50 values of iproniazid were 37 microM, and 42.5 microM in our parallel examination. Moreover, IC50 value of xanthoangelol to DBH was calculated 0.52 microM. 4-Hydroxyderricin is a potent selective MAO-B inhibitor and also mildly inhibits DBH activity. The IC50 value of 4-hydroxyderricin to MAO-B was calculated to be 3.43 microM and this value was higher than that of deprenyl (0.046 microM) used as a positive control for selective MAO-B inhibitor in our test. Cynaroside is a most potent DBH inhibitor. The IC50 value of cynaroside to DBH was calculated at 0.0410 microM. Results of this study suggest that the two prenylated chalcones, xanthoangelol and 4-hydroxyderricin isolated from A. keiskei K., are expected for potent candidates for development of combined antidepressant drug. A. keiskei K. will be an excellent new bio-functional food material that has the combined antidepressant effect.

Antidepression Action of Curcumin and Its Mechanism / 中药新药与临床药理

Objective To study the antidepression action of curcumin and to explore its mechanism. Methods Mouse reserpine-induced depression model and mouse tetrabenazine-induced acquired despair model were used to observe the effect of curcumin on relieving depression. According to the hypothesis of monoamine, the effect of curcumin on activating monoamine, and inhibiting reuptake of monoamine neurotransmitters and monoamine oxidase inhibitor (MAOI) were observed. Results Curcumin in the dose of 50 mg/kg and more can relieve melancholic symptoms in mice induced by reserpine and tetrabenazine. Curcumin had no direct activation on monoamine either had no obvious inhibition on reuptake of monoamine neurotransmitters of noradrenalin, 5-hydroxytriptamine and dopamine . However, Curcumin had an obvious effect on improving rat forelimb spasm induced by tryptamine hydrochloride. Conclusion Curcumin acts like a kind of monoamine oxidase inhibitor, which exerts antidepression action by inhibiting monoamine oxidase activity and increasing the concentration of monoamine neurotransmitter in brain.