Alkaloids of Peganum harmala L. and their Pharmacological Activity

Abstract

Peganum harmala L. contains 17 alkaloids of quinazoline and indole structure types. Of these, harmaline, harmine, harmalol and L-peganin (vazicin) are pharmacologically active. It was established that of the alkaloids contained in the seeds, 50-95% is dominated by harmaline, harmine is dominated in the 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 of alkaloids). Beta-carboline alkaloids of Peganum harmala L. inhibit monoamine oxidase, thereby exerting a neuroprotective effect.
 This article is devoted to the results of studies of the neurotropic action of harmine hydrochloride, when compared with the activity of the reference drug “Amitriptyline”. It was shown that the use of harmine hydrochloride helps to reduce the level of anxiety in animals under conditions of experimental psychoemotional chronic stress with prolonged administration. 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). According to 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 also established that harmine hydrochloride eliminates haloperidol-induced catalepsy in rats, reduces oligokinesia and rigidity in the Parkinson’s test, 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%.