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1.
Chinese Journal of Natural Medicines (English Ed.) ; (6): 194-201, 2022.
Artigo em Inglês | WPRIM | ID: wpr-929251

RESUMO

Harmaline and harmine are β-carboline alkaloids with effective pharmacological effects. Harmaline can be transformed into harmine after oral administration. However, enzymes involved in the metabolic pathway remain unclear. In this study, harmaline was incubated with rat liver microsomes (RLM), rat brain microsomes (RBM), blood, plasma, broken blood cells, and heme peroxidases including horseradish peroxidase (HRP), lactoperoxidase (LPO), and myeloperoxidase (MPO). The production of harmine was determined by a validated UPLC-ESI-MS/MS method. Results showed that heme peroxidases catalyzed the oxidative dehydrogenation of harmaline. All the reactions were in accordance with the Hill equation. The reaction was inhibited by ascorbic acid and excess H2O2. The transformation of harmaline to harmine was confirmed after incubation with blood, plasma, and broken blood cells, rather than RLM and RBM. Harmaline was incubated with blood, plasma, and broken cells liquid for 3 h, and the formation of harmine became stable. Results indicated an integrated metabolic pathway of harmaline, which will lay foundation for the oxidation reaction of dihydro-β-carboline. Moreover, the metabolic stability of harmaline in blood should not be ignored when the pharmacokinetics study of harmaline is carried out.


Assuntos
Animais , Ratos , Harmalina/metabolismo , Harmina/metabolismo , Heme , Peróxido de Hidrogênio , Espectrometria de Massas em Tandem
2.
Braz. J. Psychiatry (São Paulo, 1999, Impr.) ; 38(1): 65-72, Jan.-Mar. 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-776489

RESUMO

Objective: To conduct a systematic literature review of animal and human studies reporting anxiolytic or antidepressive effects of ayahuasca or some of its isolated alkaloids (dimethyltryptamine, harmine, tetrahydroharmine, and harmaline). Methods: Papers published until 3 April 2015 were retrieved from the PubMed, LILACS and SciELO databases following a comprehensive search strategy and using a predetermined set of criteria for article selection. Results: Five hundred and fourteen studies were identified, of which 21 met the established criteria. Studies in animals have shown anxiolytic and antidepressive effects of ayahuasca, harmine, and harmaline, and experimental studies in humans and mental health assessments of experienced ayahuasca consumers also suggest that ayahuasca is associated with reductions in anxiety and depressive symptoms. A pilot study reported rapid antidepressive effects of a single ayahuasca dose in six patients with recurrent depression. Conclusion: Considering the need for new drugs that produce fewer adverse effects and are more effective in reducing anxiety and depression symptomatology, the described effects of ayahuasca and its alkaloids should be further investigated.


Assuntos
Humanos , Animais , Ratos , Ansiolíticos/farmacologia , Banisteriopsis , Antidepressivos/farmacologia , Ansiedade/tratamento farmacológico , Ansiolíticos/uso terapêutico , N,N-Dimetiltriptamina/farmacologia , Transtorno Depressivo/tratamento farmacológico , Harmalina/farmacologia , Harmina/farmacologia , Camundongos , Antidepressivos/uso terapêutico
3.
Journal of Medicinal Plants. 2015; 14 (55): 43-57
em Inglês | IMEMR | ID: emr-173950

RESUMO

Background: Sustainable and commercial production of secondary metabolites is a critical issue when dealing with its clinical application. Efforts are still being made to look for biotic or abiotic elicitors with more efficient and universal effects on the improvement of secondary metabolites


Objective: In order to evaluate the suitability of different biotic elicitors on P. harmala L. cell suspension cultures was established to enhance the beta-carboline alkaloids [harmaline and harmine] production


Methods: The elicitation of cell suspension cultures of Peganum harmala L. was done by adding various fungal mycelium homogenates [Aspergillus flavus, Alternaria alternate, Coriolus versicolor, Fusarium oxysporum, Mucor sp, Penicillium notatum, and Rhizopus stonifer], Casein hydrolysate and Saccharomyces cerevisiae at different concentrations. The cell cultures of P. harmala L. were subcultured on MS medium with optimal treatment of biotic elicitor. CAMAG analytical HPTLC system was used for estimation of harmaline and harmine after extraction of beta-carboline alkaloids


Results: The maximum harmine production [91.2 +/- 1.8 microg g[-1] DW] was observed at 1000 mg l[-1] S. cerevisiae in cell suspension culture of P. harmala L. [1.68 fold over than the control]. Also the results showed that supplement of 75-100 mg l-1 casein hydrolysate in cell cultures media increased biomass of cell culture and harmaline and harmine production [1.61 and 1.46 times over than the control, respectively]


Conclusion: The conclusion of the research showed that by applying biotic elicitors, we can reach to higher secondary metabolites [harmaline and harmine] in cell suspension culture of P. harmala L. We suggest future investigation on using other elicitors like bacterial extract or signal transduction compounds in cell suspension culture of P. harmala L. in order to increase the production of different kind of secondary metabolites


Assuntos
Carbolinas , Alcaloides , Técnicas de Cultura de Células , Harmalina , Harmina
4.
Pakistan Journal of Pharmaceutical Sciences. 2004; 17 (1): 31-6
em Inglês | IMEMR | ID: emr-68034

RESUMO

The neuropharmacologic profile of harmala alkaloids has been studied and found to have central effects like convulsions, catalepsy, or altered startle response. In number of studies the effects of diazepam, on harmaline and other beta carboline containing compounds-induced tremors were investigated. The present study was undertaken to examine the effect of diazepam on pretreated animals with harmaline and its synthesized phenacyl and coumarine analogues. Diazepam successfully inhibited the tremor and convulsions and attenuated the other behavioural response produced by Harmaline and its derivatives


Assuntos
Animais de Laboratório , Harmalina , Camundongos , Sistema Nervoso Central/efeitos dos fármacos , Comportamento Animal
5.
Korean Journal of Physical Anthropology ; : 39-49, 2003.
Artigo em Coreano | WPRIM | ID: wpr-183129

RESUMO

The indole alkaloid harmaline has been to cause tremor and ataxia, and produce cerebellar neurotoxicity in rat. Degeneration of Purkinje cell alligned in narrow parasagittal bands result from excitation of inferior olivary nucleus in harmaline-treated rats. The objective of this study was to investigate the hypothesis that excitation of climbing fiberinduced by harmaline mediates Purkinje cell injury or degeneration. For this purpose, the inferior olive of rats was chemically ablated by using 3-acetyl pyridine, a neurotoxic chemical, and cerebellar damage followed by administration of harmaline was analyzed using immunohistochemical markers for neurons, glial cells. The results demonstrated that a subset of Purkinje cell in the vermis and paravermis degenerated after harmaline treatment, but harmaline produced little or no Purkinje cell degeneration after inferior olivary ablation. These results suggested that harmalineinduced activation of inferior olivary neurons may lead to release of glutamate from climbing fiber synaptic terminal distributed over the Purkinje cells, and may lead to cytotoxic degeneration of Purkinje cells.


Assuntos
Animais , Ratos , Ataxia , Cerebelo , Ácido Glutâmico , Harmalina , Neuroglia , Neurônios , Olea , Núcleo Olivar , Terminações Pré-Sinápticas , Células de Purkinje , Tremor
6.
Indian J Biochem Biophys ; 1998 Apr; 35(2): 86-90
Artigo em Inglês | IMSEAR | ID: sea-27134

RESUMO

The effect of harmaline, a plant alkaloid has been studied on yeast invertase activity in the absence and presence of 50mM Na+ as a function of pH. Harmaline (1-3 mM) inhibited the invertase activity at pH 5.2, 6.8 and 8 both in the absence (44-92%) and (22-85%) of Na+ ions. Kinetic analysis revealed that harmaline is a non-competitive inhibitor of invertase, at pH 5.2 and 6.8 but at pH 8, it produced a mixed type of inhibition, Km increased by 450% and 175% and Vmax decreased by 82% and 63% in the absence and presence of 50mM Na ions respectively. The observed inhibition of invertase by harmaline was reversible in nature. These findings suggest that the presence of Na+ site is not a prerequisite for the inhibition of enzyme by harmaline.


Assuntos
Glicosídeo Hidrolases/química , Harmalina/farmacologia , Concentração de Íons de Hidrogênio , Cinética , Saccharomyces cerevisiae/enzimologia , beta-Frutofuranosidase
7.
Indian J Exp Biol ; 1993 Jun; 31(6): 529-32
Artigo em Inglês | IMSEAR | ID: sea-61584

RESUMO

Intestinal uptake of lysine in rats progressively decreased with an increase in pH from 5.2 to 8.5, both in the presence and absence of Na+ ions. At pH 5.2 lysine uptake was 30-35% more than that at neutral pH. Na+ activated lysine uptake by 40-50% at pH 5.2 and it was increased to 110-120% at neutral pH. The observed increase in lysine uptake in response to Na+ and H+ gradients was due to enhanced maximal velocity (Vmax), with little change in affinity constant (Kt). Arrhenius analysis revealed a biphasic curve for lysine uptake with transition temperature (Tc) around 20 degrees C (24 degrees C at pH 5.2 in presence of Na+). The energy of activation (Ea) below (16.1-23.4 Kcal/mole) and above (6.7-8.6 Kcal/mole) the Tc was similar at pH 5.2 and 7.0 both in the presence and absence of Na+ ions. The sensitivity of lysine uptake to various inhibitors was also dependent upon pH and Na+ ions.


Assuntos
Animais , Arsenitos/farmacologia , Dinitrofenóis/farmacologia , Etilmaleimida/farmacologia , Harmalina/farmacologia , Concentração de Íons de Hidrogênio , Absorção Intestinal/efeitos dos fármacos , Iodoacetatos/farmacologia , Ácido Iodoacético , Isatina/farmacologia , Lisina/farmacocinética , Masculino , Ratos , Ratos Wistar , Sódio/farmacologia , Compostos de Sódio/farmacologia , Trocadores de Sódio-Hidrogênio/metabolismo
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