Alkaloids of peganum harmala L. and their pharmacological activity

Abstract

BACKGROUND: Peganum harmala L. contains 17 quinazoline and indole structural alkaloids. Harmaline, harmine, harmalol, and L-peganin (vasicine) are pharmacologically active. It was established that in alkaloids contained in the seeds, 50–95% falls on harmaline that harmine is dominated in roots (67–74% of the total of extractive substances), and in the aerial part, the main mass is peganin (up to 78% of the total alkaloids). Beta-carboline alkaloids of P. harmala L. inhibit monoamine oxidase, thereby exerting a neuroprotective effect. AIM: The study of the pharmacological properties of harmine hydrochloride. MATERIALS AND METHODS: The neurotropic activity of harmine hydrochloride was studied in the Porsolt’s and “elevated plus maze” tests, as well as in experimental models of haloperidol catalepsy, hypobaric hypoxia, and normobaric hypoxia. RESULTS:In the study of acute and chronic toxicity, it was determined that harmine hydrochloride belongs to the category of moderately toxic substances (hazard Class II). Based on the results of molecular docking, the presence of strong bonds in harmine hydrochloride with the serotonin 5-HT2C receptor, dopamine D2 receptor, as well as monoamine oxidase A and B was revealed, which indicates the implementation of the mechanism of neurotropic action of harmine hydrochloride at the level of synaptic neurotransmission of monoamines (dopamine, serotonin, and others). It was established that harmine hydrochloride has antihypoxic activity in the hypobaric hypoxia test and exhibits pronounced antidepressant activity in the Porsolt’s test. In the course of the study of pharmacokinetics and bioavailability, it was revealed that with the administration of harmine hydrochloride, the quantitative content is quickly achieved and the concentration of the active substance in the blood significantly increases. The relative bioavailability of harmine hydrochloride is 112.7%. CONCLUSIONS: The presented data of preclinical studies showed that harmine hydrochloride has antidepressant, antihypoxic, and antiparkinsonian effects, eliminates catalepsy caused by haloperidol in rats, and reduces oligokinesia and rigidity in the parkinsonian syndrome test. In terms of antiparkinsonian effect, harmine hydrochloride is not inferior to amitriptyline. The study of the relative bioavailability of harmine hydrochloride in experimental animals showed that harmine hydrochloride is absorbed much faster when administered orally, quickly reaching the highest concentration in blood plasma. Based on the results of molecular docking, the presence of strong bonds in harmine hydrochloride with monoamine oxidases A and B was revealed, which indicates the implementation of the mechanism of the antidepressant action of the alkaloid at the level of synoptic neurotransmission.