**Inhibitory effect on platelet aggregation : The alkaloids of P. harmala are also shown to have anti-platelet aggregation effects.[18] However, there is not so much evidence on this effect of the plant so far.
* EFFECTS ON NERVOUS SYSTEM : In traditional medicine, P. harmala has been used among societies to treat some nervous system disorders such as Parkinson's disease,[19] in psychiatric conditions[7] such as nervosity,[20] and to relieve rigorous pain.[21] The alkaloid content of P. harmala is shown to be psychoactive[22] and various in vitro and in vivo studies indicate a wide range of effects produced by P. harmala and its active alkaloids on both central and peripheral nervous system including, analgesia,[22,23] hallucination, excitation,[24] and anti-depressant effect.[25,26]. Some of these alkaloids such as harmaline, harmine, and norharmane are also endogenous compounds present in the body and since they have been found in high plasma concentrations in alcoholics,[27] drug addicts,[28] smokers,[29] and patients with Parkinson's disease,[30] they are thought to be crucially involved in various central nervous system (CNS) problems. It has been also proven that P. harmala-derived beta-carbolines interact with opioid,[21] dopamine,[24] GABA (Gamma-Aminobutyric acid),[31] 5-hydroxytryptamine, benzodiazepine, and imidazoline[32] receptors present in the nervous system and this way induce their many pharmacological effects. Moreover, these alkaloids are neuroprotective[31,33] and strong inhibitors of monoamine oxidase and this important feature makes them a preferable target in the treatment of some conditions like depression.[25]
**Mono amine oxidase inhibition and anti-depressant effect: Beta-carbolines present in P. harmala strongly inhibit monoamine oxidase enzyme that is the main factor in degradation and reuptake of monoamines like serotonin and norepinephrine. It was pointed out in an in vitro study that seed and root extracts of P. harmala significantly inhibits MAO-A but has no effect on MAO-B. In case of the seed extract the inhibitory effect was reversible and competitive with an IC50 of 27 μg/l and it was mostly attributed to harmaline and harmine. The strong inhibitory effect of the root extract was only due to harmine and the IC50 was calculated as159 μg/l.[7] It could be concluded that this inhibitory effect has the potential to reverse the MAO-mediated monoamine reduction in depression. Harmine at high doses increased the BDNF (Brain-derived neurotrophic factor) protein level, which is decreased in depressive conditions, while imipramine, a common anti-depression drug, had no such effect.[25] Farzin et al. revealed in a study on the anti-depressant effects of harmane, norharmane, and harmine using the mouse force swim test that these alkaloids of P. harmala have a significant dose-dependent anti-depressive effect with a suggested mechanism of acting on benzodiazepine receptors. It was shown in another in vitro study that the extract of P. harmala has the ability to inhibit catechol-O-methyltransferase and thereby the methylation of catecholamines with a mixed type mechanism.[34] All of these effects represent an idea that P. harmala and its derivatives could be used for treatment of mood disorders and are potent alternatives for current anti-depression drugs.
**Analgesic and antinociceptive effects : The analgesic effect of different forms of P. harmala extract (ethyl acetate [EAE], butanolic [BE], and AqE) have been investigated in various parallel studies. The methods used in these studies include formalin, hot plate, and writhing tests. The results showed that all forms of the extracts produced the analgesic effect. Among the extracts, BE showed the maximum effect with a percentage of 35.12% in the writhing test. In case of the AqE, the nociceptive effect was only observed in the second phase of the formalin test. Treatment with both EAE and BE produced a dose-dependent analgesia. Since treatment with naloxone prevented the nociceptive effect of the extracts, it is concluded that an opioid-modulated mechanism is involved. The results also indicated that the extracts act both centrally and peripherally.[21,23,35]
**Relation with Parkinson's disease : The endogenous harmala alkaloids have been proven to be involved in Parkinson's disease.[31] One study on both endogenous and exogenous beta-carbolines showed that they all have general DAT-mediated (Dopamine active transporter-mediated) dopaminergic toxicity and therefore, are involved in the pathogenesis of Parkinson's disease.[36] Adversely, it was revealed in an in vitro study that two of these endogenous compounds, norharman and 9-methylnorharman, have good anti-parkinsonism effects via inhibition of MAO-B, an enzyme involved in the production of parkinsonism-related substances from the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. However, naturally occurring beta-carbolines had almost no such inhibitory effect.[33]. In contrast, several studies on the anti-parkinsonism effect of B. caapi revealed that its beta-carboline content (harmine and harmaline) has significant effect against this disease through the inhibition of MAO-B.[37,38] Although, these beta-carbolines with anti-parkinsonism effect are also present in P. harmala, there have been no studies conducted regarding the possible effect of P. harmala isolated alkaloids against Parkinson's disease, thus far.