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Objective: To identify the phytochemical constituents of Peganum harmala L. (P. harmala) seeds extract by gas chromatography-mass spectrometer (GC-MS) and evaluate their antidepressant activity. Methods: The seeds extract was analyzed by GC-MS to identify their major chemical compounds. The antidepressant activity of P. harmala was demonstrated using the forced swim test and the adrenocorticotropic hormone analysis. After oral administration of the seeds extract and diazepam in rats, the immobility time in the forced swim test was measured and the defecation rate was estimated for all rats. Results: GC-MS analysis showed the presence of indole alkaloids (β-carboline), for exmaple harmaline (48.009%), harmine (38.440%), tetrahydroharmine (8.513%), tetrahydroharman (0.061%) and 6-methoxytetrahydro-1-norharmanone (0.057%) were present in the extract. The results showed that the P. harmala extract (100 mg/kg and 300 mg/kg) were able to reduce the immobility time (80.20 ± 9.01, 46.80 ± 8.53; P < 0.001), the adrenocorticotropic hormone rate (131.33 ± 12.72, 49.72 ± 13.03; P < 0.001) and the defecation rate (1.400 ± 1.342, 0.600 ± 0.548; P < 0.01), respectively. Conclusions: This indicates that the seeds extract can correct the depression and reach the normal state of the treated animals. The results demonstrated that seeds represented a source of indole alkaloids (harmaline, harmine and tetrahydroharmine).

Introduction The Annonaceae family is known as a promising abundant source of secondary metabolites, especially annonaceous acetogenins, terpenoids and isoquinoline-derived alkaloids. Although widely investigated from the phytochemical viewpoint, this family still presents some largely unexplored genera, e.g. the Bocageopsis. Objective To investigate the alkaloid content of Bocageopsis pleiosperma Maas using direct infusion electrospray ionisation ion trap tandem mass spectrometry (ESI-IT-MSn) analysis. Methodology Dichloromethane extracts of aerial parts were subjected to acid–base partitioning to yield the alkaloidal fractions. These fractions were analysed by direct infusion into a (+)ESI-IT-MSn system. The alkaloidal fraction from the leaves was also obtained on a large scale and subjected to chromatographic separation. Results The tentative MSn-based identification of alkaloids in leaves, twigs and trunk bark showed that aporphine alkaloids were restricted to the leaves and twigs, tetrahydroprotoberberine alkaloids were only found in the twigs and trunk bark while benzylisoquinoline alkaloids were found in the leaves, twigs and trunk bark. Chromatographic separation of the leaf alkaloidal fraction yielded the aporphine alkaloids nornuciferine, asimilobine and isoboldine, the β-carboline alkaloid tetrahydroharman and some mixtures containing benzylisoquinoline and aporphine alkaloids, all described for the first time in the Bocageopsis genus. Furthermore, tetrahydroharman has not previously been reported in the Magnoliales order. Conclusion Direct infusion ESI-IT-MSn analysis of alkaloids allowed fast recognition of alkaloidal classes previously reported in the Annonaceae family, aiding the chromatographic step and allowing a selective isolation of compounds previously not identified in the Bocageopsis genus. Copyright © 2015 John Wiley & Sons, Ltd.

A high performance liquid chromatographic method was developed to determine all types of β-carboline alkaloids in medicinal and edible plants. The alkaloids, including internal standards, were purified from plant homogenates by serial extractions after reacting with fluorescamine. The extracts were analysed twice using reversed-phase chromatography with fluorometric detection optimized for each individual analyte. β-Carbolines and tetrahydro-β-carbolines were analysed in the first run, while dihydro-β-carbolines were analysed in the second. The simultaneous separation of harmol, norharman, harman, harmine, harmalol, harmaline, tetrahydronorharman, tetrahydroharman and two internal standards was achieved within 17 min by an isocratic elution. β-Carbolines, dihydro-β-carbolines and tetrahydro-β-carbolines could be quantitatively determined in concentrations of 0.01–50.0 ng/mL. In replicate spiking experiments, the mean recovery was 71–110% and the relative standard deviation was 0.3–10.1% within and between assays. Application of the proposed method has revealed that medicinal plants and dried edible plants contain β-carboline alkaloids at ng/g to µg/g levels. Norharman and harman were distributed in all the tested plants, while harmol and harmalol were found only in some plant species. However, no significant amounts of tetrahydro-β-carbolines were detected in any plant materials tested, suggesting that the oxidation of tetrahydro-β-carbolines to β-carbolines occurs during the drying and/or the storing process. The β-carboline alkaloids may be responsible for the pharmacological effects of certain medicinal plants. Copyright © 1999 John Wiley & Sons, Ltd.

Helicobacter pylori contains alcohol dehydrogenase which oxidizes ethanol to acetaldehyde. In the present study, H . pylori cytosol was incubated in a buffered media at pH 6.0 and 7.4 in the presence of ethanol and tryptamine. Under these conditions, tetrahydroharman (1-methyl-tetrahydro-β-carboline) was produced as a condensation product of tryptamine and acetaldehyde. At pH 6.0, 20.60 ± 5.00% of the added tryptamine was converted to tetrahydroharman, while 27.00 ± 4.80% (mean ± SD) was converted at pH 7.4. Similar reactions between acetaldehyde and other dietary amines seem likely. Such biogenic alkaloids, if formed in vivo , might contribute to the dysphoric effects of alcohol.

There is a general consensus in dentistry that successful local anesthesia is frequently difficult in habitual drinkers and alcoholic patients. Neuro-active tetrahydroharmans increase in human body fluids and tissues by consuming alcoholic beverages. To understand such reduced anesthetic efficacy by the drug interaction hypothesis, we studied the influences of drinking-related tetrahydroharmans on membrane fluidization as one of local anesthetic mechanisms. Liposomal membranes prepared with phosphatidylcholine and cholesterol were treated with lidocaine and different tetrahydroharmans separately and in combination, followed by measuring fluorescence polarization to determine their induced changes in membrane fluidity. In contrast to 0.1–2 mg/mL lidocaine, tetrahydroharmans decreased the fluidity of membrane preparations at ∼25 μg/mL with the potency being 1,2,3,4-tetrahydroharman ≫ 1,2,3,4-tetrahydronorharman. 1,2,3,4-Tetrahydroharman counteracted the membrane-fluidizing effects of 1 mg/mL lidocaine at physiologically relevant 0.25–2.5 ng/mL, whereas neither its 6-hydroxyl nor 7-hydroxyl metabolite did at 25–200 ng/mL. Such counteraction at a membrane lipid level may be responsible for the reduction of local anesthetic efficacy in drinkers because 1,2,3,4-tetrahydroharman increases in vivo by ingesting alcoholic beverages.

Summary 4-Dimethylaminoazobenzene is only a weak mutagen on Salmonella typhimurium strains TA100 and TA98, although it is a fairly strong carcinogen. Norharman, which is present in tobacco smoke and tryptophan pyrolysate, enhanced the mutagenicity of 4-dimethylaminoazobenzene on strain TA98 about 40-fold. Norharman alone had no mutagenic activity on TA98 and so it is a ‘Comutagen’. The mutagenicities of 4-methylaminoazobenzene, 3′-methyl-4-dimethylaminoazobenzene, 4-aminoazobenzene and 4′-methoxycarbonyl-N-hydroxy-4-methylaminoazobenzene were all potentiated by norharman. Presence of a metabolic activation system was essential for comutagenic action of norharman with these compounds. Dihydronorharman, tetrahydronorharman, 9-methyl-β-carboline, harman and tetrahydroharman did not enhance the mutagenicity of 4-dimethylaminoazobenzene.

The β-carboline alkaloid harman has been shown by a combination of feeding and trapping experiments to be formed in Passiflora edulis from N-acetyltryptamine via harmalan. N-acetyltryptamine was shown to be formed from tryptophan via tryptamine. Tetrahydroharman is dehydrogenated to harman presumably via harmalan. Radioactive harman obtained from 14C labelled N-acetyltryptamine, harmalan and tetrahydroharman was degraded to establish the position of the label and doubly labelled tryptophan was converted to N-acetyl tryptamine containing the same ration of 3H: 14C.

In addition to a very much larger amount of calycanthine, the seeds of Calycanthus floridus contain 0.03% of a simpler alkaloid C18H16N2, related to tetrahydroharman.

1-Methyl-1,2,3,4-tetrahydro-beta-carboline (tetrahydroharman) has been quantified in human platelets and plasma following acute intake of ethanol using a selective ion monitoring method. It was not possible to detect this compound before ethanol intake.

A spectrophotometric method for the quantitative determination of the alkaloids of the β-carboline series (harman and tetrahydroharman) in preparations and in the root ofElaeagnus angustifolia L. at various phases of development of the plant has been developed.

1-Methyl-1,2,3,4-tetrahydro-β-carboline-1-carboxylic acid (1-carboxytetrahydroharman, 1-CTHH) has been detected in the brain of rats following intracerebroventricular injection of tryptamine and pyruvic acid. We now report the metabolism of this compound. Following intraperitoneal injection of 1-CTHH into rats, harmalan was found to be the major metabolite besides tetrahydroharman (THH) and harman. A high concentration of THH was measured in the lung while most of harman was found in the urine. Harmalan and THH could be detected in the brain in low concentrations. The products were separated following extraction from tissues by high-performance liquid chromatography (HPLC) on a reversed phase C18-DB column. The identity of the metabolites was confirmed by mass spectrometry (MS) analysis. The results demonstrate the role of 1-CTHH as a precursor of the biologically active compounds harmalan, THH and harman.

In vivo metabolism of 1-methyl-1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (1-CTHH), a possible precursor of the endogenous beta-carbolines tetrahydro-harman (THH) and harman was investigated in rats. Following intraperitoneal injection of [4-14C]1-CTHH, a rapid distribution of the radioactivity in the tissues was observed. The highest radioactivity was measured in the kidney and the lowest in the brain as well as in the fat tissue. Approximately 55% of the administered dose was excreted in the urine within 90 min. The radioactivity in the urine consisted of unchanged 1-CTHH (greater than 90%) besides harmalan and trace amounts of harman. Harmalan represents the major degradation product of 1-CTHH; it could be identified in all tissues examined and in the urine. The concentration in the blood, however, was low at all time points investigated. The peak concentration of harmalan in most tissues was measured between 15-30 min after injection. A time-dependent formation of THH was found in the lung and spleen indicating an important role of these organs in the biosynthesis of THH. Furthermore, the metabolism of [4-14C]1-CTHH in the brain was studied following intracerebroventricular injection. The formation of harmalan in the brain was not affected by pretreatment with the aromatic amino acid decarboxylase inhibitor NSD 1015. Determination of the harmalan concentration in several brain regions revealed a high level in the hippocampus and hypothalamus and a small concentration in pons, corpus striatum, cerebellum and cerebral cortex 20 min after injection. The analyses of the