RESUMO
Harman, a natural ß-carboline alkaloid, has recently gained considerable interest due to its anticancer properties. However, its physicochemical characteristics and poor oral bioavailability have been limiting factors for its pharmaceutical development. In this paper, we described the complexation of harman (HAR) with ß-cyclodextrin (ßCD) as a promising alternative to improve its solubility and consequently its cytotoxic effect in chemoresistant melanoma cells (A2058 cell line). Inclusion complexes (ßCD-HAR) were prepared using a simple method and then characterized by FTIR, NMR and SEM techniques. Through in silico studies, the mechanism of complexation of HAR with ßCD was elucidated in detail. Both HAR and ßCD-HAR promoted cytotoxicity, apoptosis, cell cycle arrest and inhibition of cell migration in melanoma cells. Interestingly, complexation of HAR with ßCD enhanced its pro-apoptotic effect by increasing of caspase-3 activity (p < 0.05), probably due to an improvement in HAR solubility. In addition, HAR and ßCD-HAR sensitized A2058 cells to vemurafenib, dacarbazine and 5FU treatments, potentializing their cytotoxic activity. These findings suggest that complexation of HAR with natural polymers such as ßCD can be useful to improve its bioavailability and antimelanoma activity.
Assuntos
Antineoplásicos/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Harmina/análogos & derivados , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , beta-Ciclodextrinas/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Harmina/administração & dosagem , Harmina/química , Humanos , Melanoma/genética , Simulação de Dinâmica Molecular , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias Cutâneas/genética , beta-Ciclodextrinas/químicaRESUMO
The use of the hallucinogenic brew ayahuasca, obtained from infusing the shredded stalk of the malpighiaceous plant Banisteriopsis caapi with the leaves of other plants such as Psychotria viridis, is growing in urban centers of Europe, South and North America in the last several decades. Despite this diffusion, little is known about its effects on emotional states. The present study investigated the effects of ayahuasca on psychometric measures of anxiety, panic-like and hopelessness in members of the Santo Daime, an ayahuasca-using religion. Standard questionnaires were used to evaluate state-anxiety (STAI-state), trait-anxiety (STAI-trait), panic-like (ASI-R) and hopelessness (BHS) in participants that ingested ayahuasca for at least 10 consecutive years. The study was done in the Santo Daime church, where the questionnaires were administered 1h after the ingestion of the brew, in a double-blind, placebo-controlled procedure. While under the acute effects of ayahuasca, participants scored lower on the scales for panic and hopelessness related states. Ayahuasca ingestion did not modify state- or trait-anxiety. The results are discussed in terms of the possible use of ayahuasca in alleviating signs of hopelessness and panic-like related symptoms.
Assuntos
Ansiedade/tratamento farmacológico , Banisteriopsis/química , Transtorno Depressivo/tratamento farmacológico , Pânico/efeitos dos fármacos , Extratos Vegetais/farmacologia , Adulto , Ansiedade/psicologia , Bebidas , Brasil , Transtorno Depressivo/psicologia , Método Duplo-Cego , Feminino , Frutas/química , Harmalina/administração & dosagem , Harmalina/química , Harmalina/farmacologia , Harmina/administração & dosagem , Harmina/análogos & derivados , Harmina/química , Harmina/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Estrutura Molecular , N,N-Dimetiltriptamina/administração & dosagem , N,N-Dimetiltriptamina/química , N,N-Dimetiltriptamina/farmacologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Folhas de Planta/química , Psicometria/métodos , Religião , Inquéritos e Questionários , Resultado do TratamentoRESUMO
beta-carboline alkaloids are found in several medicinal plants and display a variety of actions on the central nervous, muscular and cardiovascular systems. The aim of the present study was to evaluate the effects of systemic administration of beta-carboline alkaloids on object recognition in mice. Adult Swiss mice received an intra-peritoneal injection (i.p.) of alkaloids (1.0, 2.5 or 5.0 mg/kg) 30 min before training in an object recognition task. The fully aromatic beta-carbolines, harmine and harmol, induced an enhancement of short-term memory (STM) at all doses tested when compared to controls. Harmaline, a dihydro beta-carboline and inverse agonist of the MK-801 binding site on the N-methyl-d-aspartate (NMDA) receptor, also induced an enhancement of both short-term memory (STM) and long-term memory (LTM). These results demonstrate that systemic administration of beta-carboline alkaloids can improve object recognition memory in mice.
Assuntos
Alcaloides/farmacologia , Carbolinas/farmacologia , Harmalina/farmacologia , Harmina/farmacologia , Reconhecimento Psicológico/fisiologia , Alcaloides/administração & dosagem , Animais , Carbolinas/administração & dosagem , Harmalina/administração & dosagem , Harmina/administração & dosagem , Injeções Intraperitoneais , Masculino , Camundongos , Modelos Animais , Reconhecimento Psicológico/efeitos dos fármacosRESUMO
Although it has been known for many years that hallucinogenic drugs are used by witch doctors in the Peruvian jungles for therapeutic purposes, there have been no descriptions of their use. We studied one type of treatment carried out in groups of about 10 to 12 'patients', where the healer makes a magical diagnosis and provides a potion, usually ayahuasca (active hallucinogenic agent: harmine) which is drunk by the witch doctor, his assistant and the patients. The groups meet one a week in the open air in the jungle, at dawn and for an average of 5 h. The patient attends the weekly sessions until he feels well enough to leave, and only then does he pay a voluntary fee. One of our main tasks was to study the group processes.