RESUMO
Under natural conditions plants are generally subjected to complex scenarios of combined or sequential environmental stresses. Among the various components of plant biochemistry modulated by abiotic variables, a pivotal role is played by antioxidant systems, including specialized metabolites and their interaction with central pathways. To help address this knowledge gap, a comparative analysis of metabolic changes in leaf tissues of the alkaloid accumulating plant Psychotria brachyceras Müll Arg. under individual, sequential, and combined stress conditions was carried out. Osmotic and heat stresses were evaluated. Protective systems (accumulation of the major antioxidant alkaloid brachycerine, proline, carotenoids, total soluble protein, and activity of the enzymes ascorbate peroxidase and superoxide dismutase) were measured in conjunction with stress indicators (total chlorophyll, ChA/ChB ratio, lipid peroxidation, H2O2 content and electrolyte leakage). Metabolic responses had a complex profile in sequential and combined stresses compared to single ones, being also modified over time. Different stress application schemes affected alkaloid accumulation in distinct ways, exhibiting similar profile to proline and carotenoids, constituting a complementary triad of antioxidants. These complementary non-enzymatic antioxidant systems appeared to be essential for mitigating stress damage and re-establishing cellular homeostasis. The data herein provides clues that may aid the development of a key component framework of stress responses and their appropriate balance to modulate tolerance and yield of target specialized metabolites.
Assuntos
Alcaloides , Psychotria , Antioxidantes/metabolismo , Psychotria/química , Psychotria/metabolismo , Peróxido de Hidrogênio/metabolismo , Alcaloides/metabolismo , Carotenoides/análise , Carotenoides/metabolismo , Folhas de Planta/metabolismo , Prolina/análise , Prolina/metabolismoRESUMO
The current article presents a mixed qualitative-quantitative observational study of the effect of ayahuasca ritual on subjective experiences and personality traits on participants of a center specialized in the treatment of substance use disorder in Uruguay. When comparing the psychological traits of ayahuasca participants to a control group, quantitative results using the Zuckerman-Kuhlman-Aluja Personality Questionnaire showed statistically significant higher scores in Impulsive Sensation Seeking, Boredom Susceptibility, and Social Warmth scales. Qualitative analysis of ayahuasca experiences resulted in five main categories: emotional experiences (including social emotions such as love and empathy), corporal experiences, spiritual/transcendental experiences, personal experiences, and visions. Last, qualitative descriptions provide support for the importance of social interactions in the phenomenological manifestations of the psychedelic experience. Both quantitative and qualitative results suggest that the combination of social interactions and the pharmacological action of ayahuasca could facilitate the manifestation of social emotions during the ritual, and may contribute to the long-term increase of empathic and social aspects of personality.
Assuntos
Medicina Herbária , Personalidade , Comportamento Social , Transtornos Relacionados ao Uso de Substâncias , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Uruguai , Humanos , Amor , Empatia , Banisteriopsis/química , Psychotria/química , Comportamento Impulsivo , Tédio , Medicina Tradicional , Extroversão Psicológica , Masculino , Feminino , AdultoRESUMO
The use of natural products for medicinal purposes is becoming more and more common nowadays, as evidenced by the presence in plants of secondary metabolites with different potentials such as antioxidant and antibacterial properties. We evaluated in this work the antimicrobial activities of the extracts and some isolated compounds from the seeds of Psychotria succulenta Hiern. (Rubiaceae), a Cameroonian medicinal plant traditionally used to cure microbial infections. The ethanol extract was prepared by maceration and extracted with ethyl acetate and n-butanol. The EtOAc (m = 168 g) and n-BuOH (m = 20 g) extracts were further fractionated by silica gel column chromatography to isolation of compounds. Their structures were elucidated by spectroscopic analysis and by comparison with published data. The antibacterial activity of extracts and compounds was assessed by evaluating the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against pathogenic bacteria. Thirteen compounds including four alkaloids (veprisine (1), naucleofficine III (2), vepridimerine B (3), and vepridimerine C (4)), three triterpenes (barbinervic acid (5), 3-O-α-L-rhamnopyranosyl quinovic acid (6), and oleanolic acid (7)), one steroid (ß-sitosterol-3-O-ß-D-glucopyranoside (8)), four phenolic compounds (scopoletin (9), gallic acid (10), quercetin-3-O-ß-D-glucopyranoside (11), and kaempferol 3-O-α-L-rhamnopyranoside-7-O-α-L-rhamnopyranoside (12)), and one iridoid (borreriagenin (13)) were isolated from the EtOAc and n-BuOH extracts. These compounds were identified by 1D and 2D NMR combined analysis as well as by melting point comparison. The EtOH, EtOAc, and n-BuOH extracts exhibited significant antibacterial activities (MIC = 32-128 µg/mL; MBC = 64-256 µg/mL) against Staphylococcus aureus (Gram-positive bacterium), Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumonia (Gram-negative bacteria). Among the isolated compounds, scopoletin (9) showed a moderate activity against Klebsiella pneumoniae with MIC and MBC values of 16 µg/mL and 32 µg/mL, respectively. It appears that, chemotaxonomically, some of the isolated compounds have already been obtained from the genus Psychotria but to the best of our knowledge, this is the first report on the phytochemical investigation of P. succulenta. Although many other studies need to be achieved, our results support the use of P. succulenta in traditional medicine to cure infectious diseases particularly those caused by the tested bacteria.
Assuntos
Psychotria , Rubiaceae , Antibacterianos/química , Bactérias , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , EscopoletinaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Leaves from Psychotria poeppigiana Müll. Arg. (accepted as Palicourea tomentosa (Aubl.) Borhidi), Rubiaceae, has traditionally been used in medicine for treatments of inflammation and pain; Synonymously, Cephaelis elata for the treatment of dementia; However, few scientific studies have been evidence demonstrating this activity. AIM OF THE STUDY: The aim of this study was to investigate the chemical composition of P. poeppigiana essential oil obtained from leaves (EOPP) and its antioxidant, anti-inflammatory and acetylcholinesterase (AChE) activities. Molecular docking simulations were carried out with the main constituents. MATERIALS AND METHODS: EOPP (hydrodistillation) was analysed by gas chromatography-mass spectrometry (GC-MS). The fractionation of EOPP afforded germacrene D and bicyclogermacrene. The antioxidant activity of EOPP was determined by MDA assay. The inflammatory parameters were evaluated using CFA model (with paw edema, mechanical, thermal hyperalgesia, MPO and NAG) in EOPP (30, 100 and 300 mg/kg), germacrene D and bicyclogermacrene (30 mg/kg). The AChE inhibition was evaluated in rat brain structures and molecular docking simulations were carried out using Autodock v.4.3.2. RESULTS: GC-MS analysis identified 19 compounds, and the major compounds were germacrene D (29.38%) and bicyclogermacrene (25.21%). EOPP exhibited high antioxidant capacity (IC50 = 12.78 ± 1.36 µg/mL). All the tested doses of EOPP and both major constituents significantly inhibited cold and mechanical hyperalgesia and significantly blocked the increase in MPO activity 24 h after the CFA injection. There was significant AChE inhibition by EOPP and germacrene D in the cerebral cortex and hippocampus (>50%). Enzyme-ligand molecular modelling showed that the major constituents of EOPP interacted differently with AChE. CONCLUSIONS: The chemical compounds of the essential oil from the leaves of P. poeppigiana is based mainly on terpenes, the sesquiterpenes germacrene D (29.38%) and bicyclogermacrene (25.21%) being the major compounds. EOPP presented antioxidant, anti-inflammatory and anti-acetylcholinesterase (AChE) activities. Besides, enzyme-ligand molecular modelling showed the EOPP may act as an anti-hyperalgesic and AChE inhibitory agent. Taken together, these results might be in accordance with if folk use for pain- and inflammation-related symptoms.
Assuntos
Óleos Voláteis , Psychotria , Acetilcolinesterase , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Ligantes , Simulação de Acoplamento Molecular , Óleos Voláteis/química , Dor/tratamento farmacológico , Folhas de Planta/química , RatosRESUMO
The leaf homogenate of Psychotria insularum is widely used in Samoan traditional medicine to treat inflammation associated with fever, body aches, swellings, wounds, elephantiasis, incontinence, skin infections, vomiting, respiratory infections, and abdominal distress. However, the bioactive components and underlying mechanisms of action are unknown. We used chemical genomic analyses in the model organism Saccharomyces cerevisiae (baker's yeast) to identify and characterize an iron homeostasis mechanism of action in the traditional medicine as an unfractionated entity to emulate its traditional use. Bioactivity-guided fractionation of the homogenate identified two flavonol glycosides, rutin and nicotiflorin, each binding iron in an ion-dependent molecular networking metabolomics analysis. Translating results to mammalian immune cells and traditional application, the iron chelator activity of the P. insularum homogenate or rutin decreased proinflammatory and enhanced anti-inflammatory cytokine responses in immune cells. Together, the synergistic power of combining traditional knowledge with chemical genomics, metabolomics, and bioassay-guided fractionation provided molecular insight into a relatively understudied Samoan traditional medicine and developed methodology to advance ethnobotany.
Assuntos
Anti-Inflamatórios/análise , Flavonoides/isolamento & purificação , Quelantes de Ferro/análise , Fenóis/isolamento & purificação , Psychotria/química , Rutina/isolamento & purificação , Animais , Avaliação Pré-Clínica de Medicamentos , Etnobotânica , Feminino , Genômica , Masculino , Medicina Tradicional , Metabolômica , Camundongos Endogâmicos C57BL , Plantas Medicinais/química , Saccharomyces cerevisiae , SamoaRESUMO
After a century of investigations, the function of the obligate betaproteobacterial endosymbionts accommodated in leaf nodules of tropical Rubiaceae remained enigmatic. We report that the α-D-glucose analogue (+)-streptol, systemically supplied by mature Ca. Burkholderia kirkii nodules to their Psychotria hosts, exhibits potent and selective root growth inhibiting activity. We provide compelling evidence that (+)-streptol specifically affects meristematic root cells transitioning to anisotropic elongation by disrupting cell wall organization in a mechanism of action that is distinct from canonical cellulose biosynthesis inhibitors. We observed no inhibitory or cytotoxic effects on organisms other than seed plants, further suggesting (+)-streptol as a bona fide allelochemical. We propose that the suppression of growth of plant competitors is a major driver of the formation and maintenance of the Psychotria-Burkholderia association. In addition to potential agricultural applications as a herbicidal agent, (+)-streptol might also prove useful to dissect plant cell and organ growth processes.
Assuntos
Alelopatia/fisiologia , Burkholderia/metabolismo , Cicloexanóis/farmacologia , Feromônios/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Folhas de Planta/microbiologia , Psychotria/química , Psychotria/microbiologia , Simbiose/fisiologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/crescimento & desenvolvimento , Germinação/efeitos dos fármacos , Lactuca/efeitos dos fármacos , Lactuca/crescimento & desenvolvimento , Meristema/efeitos dos fármacos , Meristema/crescimento & desenvolvimento , Mostardeira/efeitos dos fármacos , Mostardeira/crescimento & desenvolvimento , Filogenia , Folhas de Planta/metabolismo , Psychotria/metabolismo , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimentoRESUMO
INTRODUCTION: A great variety of bioactive natural products has been reported for different Palicourea and Psychotria species (Rubiaceae). However, few of them as well as few of species of these botanical genera have been evaluated for antiplasmodial activity. OBJECTIVE: To assess the antiplasmodial activity of 24 extracts from Palicourea and Psychotria genera, along with the targeted LC-MS metabolite profiling, as well as identification of the main metabolites in the bioactive extracts. METHODS: Twenty four ethanol and acid-base extracts from Palicourea and Psychotria genera collected in the Amazonia and Atlantic Forest, Brazil, were evaluated against chloroquine-resistant Plasmodium falciparum W2 strain by PfLDH. The metabolite profiling and putative identification of metabolites from bioactive extracts were determined by LC-DAD-ESI-MS and LC-HRMS, respectively. RESULTS: The ethanol extracts disclosed low antiplasmodial activity (% GI < 50%). High antiplasmodial effect was observed for the acid-base extracts from Psychotria apoda and Psychotria colorata with 100% inhibition of parasite growth inhibition. Fragment ions related to pyrrolidinoindoline alkaloids were observed by LC-DAD-ESI-MS mainly in the most bioactive extracts. The results of the in vitro screening associated with the LC-DAD-ESI-MS and LC-HRMSn data allowed to predict, for the first time, the pyrrolidinoindoline alkaloids as possible antiplasmodial representing, then, new potential natural antimalarial hits. In addition, other metabolite classes such as flavanones, lignans and chalcones were also putatively identified in the bioactive extracts of Psychotria apoda, Psychotria capitata, and Psychotria poeppigiana. CONCLUSION: The present results point to Palicourea and Psychotria species as sources of new antimalarial hits.
Assuntos
Alcaloides , Antimaláricos , Produtos Biológicos , Psychotria , Rubiaceae , Alcaloides/farmacologia , Antimaláricos/farmacologia , Brasil , Cromatografia Líquida , Ecossistema , Etanol , Florestas , Extratos Vegetais/farmacologia , Folhas de Planta , Espectrometria de Massas em TandemRESUMO
Zika virus (ZIKV) is a public health problem due to its association with serious fetal and neurological complications and the lack of antiviral agents and licensed vaccines against this virus. Surveillance studies have alerted about the potential occurrence of a new South American epidemic episode due to the recent circulation of an African ZIKV strain detected in Brazil. Therefore, it is essential to discover antiviral agents, including natural substances, that are capable of neutralizing the action of ZIKV. Several Psychotria species have antimicrobial and anti-inflammatory properties. Thus, a methanol extract and dimethyltryptamine from Psychotria viridis were evaluated for their ability to inhibit ZIKV infection in vitro by measuring the effective concentration that protects 50% of cells and investigating their possible mechanisms of action. The tested samples showed antiviral activity against ZIKV. The extract showed virucidal activity, affecting viral and non-cellular elements, inactivating the virus before infection or when it becomes extracellular after the second cycle of infection. It was also observed that both extract and dimethyltryptamine could inhibit the virus at intracellular stages of the viral cycle. In addition to dimethyltryptamine, it is believed that other compounds also contribute to the promising virucidal effect observed for the methanol extract. To our knowledge, this is the first report of the activity of a methanolic extract and dimethyltryptamine from Psychotria viridis against cellular ZIKV infection. These two samples, extracted from natural sources, are potential candidates for use as antiviral drugs to inhibit ZIKV infections.
Assuntos
Psychotria , Infecção por Zika virus , Zika virus , Antivirais/farmacologia , Antivirais/uso terapêutico , Humanos , Metanol , N,N-Dimetiltriptamina/uso terapêutico , Extratos Vegetais/farmacologia , Infecção por Zika virus/tratamento farmacológicoRESUMO
A substantial number of epileptic patients are resistant to the current medication thus necessitating the search for alternative therapies for intractable forms of the disease. Previous studies demonstrated the acute anticonvulsant properties of the methanol extract of the stem bark of Psychotria camptopus (MEPC) in rats. This study investigated the effects of MEPC on pentylenetetrazole-kindled Wistar rats. Kindling was induced by intraperitoneal injection of pentylenetetrazole (37.5 mg/kg) on every alternate day, 1 h after each daily oral pretreatment of rats (8 ≤ n ≤ 10) with MEPC (40, 80 and 120 mg/kg), vehicle or diazepam (3 mg/kg) for 43 days. The kindling development was monitored based on seizure episodes and severity. Rats' brains were collected on day 43 for the determination of oxidative stress parameters. The histomorphological features and neuronal cell viability of the prefrontal cortex (PFC) and hippocampus were also assessed using H&E and Cresyl violet stains. Chronic administration of pentylenetetrazole time-dependently decreased the latency to myoclonic and generalized seizures, and increased seizure scores and the number of kindled rats. MEPC and diazepam significantly increased the latencies to myoclonic jerks and generalized tonic-clonic seizures. These substances also reduced seizure score and the number of rats with PTZ-kindling. MEPC improved glutathione status and decreased lipid peroxidation in the brains of kindled rats. MEPC also exhibited neuroprotection against pentylenetetrazole-induced hippocampal and PFC neuronal damages. These results suggest that P. camptopus has antiepileptogenic activity, which might be related to the augmentation of antioxidant and neuroprotective defense mechanisms, and further confirm its usefulness in the management of epilepsy.
Assuntos
Excitação Neurológica , Fármacos Neuroprotetores , Psychotria , Rubiaceae , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Humanos , Masculino , Metanol/farmacologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Pentilenotetrazol/farmacologia , Casca de Planta , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos WistarRESUMO
ETHNOPHARMACOLOGY RELEVANCE: The decoction from the stem bark of Psychotria camptopus (Rubiaceae) is used in the Cameroonian pharmacopoeia to treat neurological pathologies including epilepsy. AIM: The present work was undertaken to study the anticonvulsant properties of the aqueous (AE) and methanol (ME) extracts from the stem bark of P. camptopus in acute models of epileptic seizures in Wistar rats. METHOD: AE and ME were obtained by decoction and maceration of the stem bark powder in water and methanol, respectively. They were tested orally at the doses of 40, 80 and 120 mg/kg, on the latency of onset and duration of epileptic seizures induced by pentylene tetrazole (PTZ, 70 mg/kg, i.p.). The kinetic effect of both extracts at 120 mg/kg was evaluated. Their effects on diazepam (50 mg/kg) induced sleep and strychnine (STR, 2.5 mg/kg, i.p.) induced seizures were determined. ME was further tested on picrotoxin (PIC, 7.5 mg/kg, i.p.) and thiosemicarbazide (TSC, 50 mg/kg, i.p.) induced seizure models. The phytochemical composition of ME was assessed using LC-MS method, as well as its acute toxicity. RESULTS: AE and ME significantly (p < 0.001) reduced the duration of seizures in both PTZ and STR models. Their maximal effect was observed at 1 h after administration, though their effect at 120 mg/kg was maintained (p < 0.05) up to 24 h post-treatment. Both extracts significantly (p < 0.01) reduced sleep duration. ME significantly (p < 0.001) increased the latency of rat death on PIC-induced convulsions. In TSC rats, ME significantly (p < 0.001) delayed the latency to the first convulsion, and decreased the duration and frequency of convulsions. ME showed no acute toxicity while its phytochemical screening revealed the presence of two flavonoids (Rutin and Butin), two triterpenoid saponins (Psycotrianoside B and Bauerenone) and four alkaloids (10-Hydroxy-antirhine, 10-hydroxy-iso-deppeaninol, Emetine and Hodkinsine). In conclusion, AE and ME from the stem bark of P. camptopus have comparable anticonvulsant properties. The effect of ME is likely due to the presence of flavonoids and alkaloid and the activation of GABA pathway. These results further justify and support the use of P. camptopus in traditional medicine for the treatment of epilepsy.
Assuntos
Anticonvulsivantes/farmacologia , Epilepsia/tratamento farmacológico , Extratos Vegetais/farmacologia , Psychotria/química , Convulsões/tratamento farmacológico , Animais , Anticonvulsivantes/uso terapêutico , Anticonvulsivantes/toxicidade , Comportamento Animal/efeitos dos fármacos , Diazepam/farmacologia , Diazepam/uso terapêutico , Modelos Animais de Doenças , Epilepsia/induzido quimicamente , Metanol/química , Camundongos , Pentilenotetrazol/toxicidade , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Picrotoxina/toxicidade , Casca de Planta/química , Extratos Vegetais/uso terapêutico , Extratos Vegetais/toxicidade , Caules de Planta/química , Ratos Wistar , Convulsões/induzido quimicamente , Semicarbazidas/toxicidade , Sono/efeitos dos fármacos , Latência do Sono/efeitos dos fármacos , Estricnina/toxicidade , Água/químicaRESUMO
Psychotria malayana Jack has traditionally been used to treat diabetes. Despite its potential, the scientific proof in relation to this plant is still lacking. Thus, the present study aimed to investigate the α-glucosidase inhibitors in P.malayana leaf extracts using a metabolomics approach and to elucidate the ligand-protein interactions through in silico techniques. The plant leaves were extracted with methanol and water at five various ratios (100, 75, 50, 25 and 0% v/v; water-methanol). Each extract was tested for α-glucosidase inhibition, followed by analysis using liquid chromatography tandem to mass spectrometry. The data were further subjected to multivariate data analysis by means of an orthogonal partial least square in order to correlate the chemical profile and the bioactivity. The loading plots revealed that the m/z signals correspond to the activity of α-glucosidase inhibitors, which led to the identification of three putative bioactive compounds, namely 5'-hydroxymethyl-1'-(1, 2, 3, 9-tetrahydro-pyrrolo (2, 1-b) quinazolin-1-yl)-heptan-1'-one (1), α-terpinyl-ß-glucoside (2), and machaeridiol-A (3). Molecular docking of the identified inhibitors was performed using Auto Dock Vina software against the crystal structure of Saccharomyces cerevisiae isomaltase (Protein Data Bank code: 3A4A). Four hydrogen bonds were detected in the docked complex, involving several residues, namely ASP352, ARG213, ARG442, GLU277, GLN279, HIE280, and GLU411. Compound 1, 2, and 3 showed binding affinity values of -8.3, -7.6, and -10.0 kcal/mol, respectively, which indicate the good binding ability of the compounds towards the enzyme when compared to that of quercetin, a known α-glucosidase inhibitor. The three identified compounds that showed potential binding affinity towards the enzymatic protein in molecular docking interactions could be the bioactive compounds associated with the traditional use of this plant.
Assuntos
Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Extratos Vegetais/farmacologia , Psychotria/química , alfa-Glucosidases/metabolismo , Simulação por Computador , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Metabolômica , Simulação de Acoplamento Molecular , Estrutura Molecular , Análise Multivariada , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/químicaRESUMO
The plant Psychotria malayana Jack belongs to the Rubiaceae family and is known in Malaysia as "meroyan sakat/salung". A rapid analytical technique to facilitate the evaluation of the P. malayana leaves' quality has not been well-established yet. This work aimed therefore to develop a validated analytical technique in order to predict the alpha-glucosidase inhibitory action (AGI) of P. malayana leaves, applying a Fourier Transform Infrared Spectroscopy (FTIR) fingerprint and utilizing an orthogonal partial least square (OPLS). The dried leaf extracts were prepared by sonication of different ratios of methanol-water solvent (0, 25, 50, 75, and 100% v/v) prior to the assessment of alpha-glucosidase inhibition (AGI) and the following infrared spectroscopy. The correlation between the biological activity and the spectral data was evaluated using multivariate data analysis (MVDA). The 100% methanol extract possessed the highest inhibitory activity against the alpha-glucosidase (IC50 2.83 ± 0.32 µg/mL). Different bioactive functional groups, including hydroxyl (O-H), alkenyl (C=C), methylene (C-H), carbonyl (C=O), and secondary amine (N-H) groups, were detected by the multivariate analysis. These functional groups actively induced the alpha-glucosidase inhibition effect. This finding demonstrated the spectrum profile of the FTIR for the natural herb P. malayana Jack, further confirming its medicinal value. The developed validated model can be used to predict the AGI of P. malayana, which will be useful as a tool in the plant's quality control.
Assuntos
Inibidores Enzimáticos/química , Inibidores de Glicosídeo Hidrolases/química , Extratos Vegetais/química , Psychotria/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Inibidores Enzimáticos/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Concentração Inibidora 50 , Análise dos Mínimos Quadrados , Análise Multivariada , Folhas de Planta/química , Solventes , alfa-GlucosidasesRESUMO
Phytochemical investigation of the alkaloid extract of the aerial parts of Psychotria nemorosa led to the isolation and characterization of 10 azepine-indole alkaloids, i.e., cimitrypazepine (1), fargesine (2), nemorosines A (3), and B (12), nemorosinosides A-F (4-9), as well as two ß-carboline derivatives, 10-hydroxyisodolichantoside (10) and 10-hydroxydolichantoside (11), an isoxazole alkaloid, nemorosinoside G (13), serotonin (14), bufotenine (15), and (S)-gentianol (16). Compounds 3-13 have not yet been described. These compounds were isolated by semipreparative HPLC, and their structures were determined by means of HRMS, NMR, and ECD measurements. In addition, the monoamine oxidase-A (MAO-A), MAO-B, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activities were evaluated. Alkaloids 1-3 inhibited the MAO-A activity with IC50 values of 1.4, 1.4, and 0.9 µM, respectively.
Assuntos
Azepinas/química , Azepinas/farmacologia , Alcaloides Indólicos/química , Alcaloides Indólicos/farmacologia , Psychotria/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacologia , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
ETHNOPHARMACOLOGY RELEVANCE: Ayahuasca is a tea produced through decoction of Amazonian plants. It has been used for centuries by indigenous people of South America. The beverage is considered to be an ethnomedicine, and it is traditionally used for the treatment of a wide range of diseases, including neurological illness. Besides, some scientific evidence suggests it may be applicable to Parkinson's disease (PD) treatment. Thus, Ayahuasca deserves in depth studies to clarify its potential role in this disease. AIM OF THE STUDY: This study aimed to use an untargeted metabolomics approach to evaluate the neuroprotective potential of the Ayahuasca beverage, the extracts from its matrix plants (Banisteriopsis caapi and Psychotria viridis), its fractions and its main alkaloids on the viability of SH-SY5Y neuroblastoma cells in an in vitro PD model. MATERIAL AND METHODS: The cytotoxicity of Ayahuasca, crude extracts, and fractions of B. caapi and P. viridis, as well as neuroprotection promoted by these samples in a 6-hydroxydopamine (6-OHDA)-induced neurodegeneration model, were evaluated by the MTT assay at two time-points: 48 h (T1) and 72 h (T2). The main alkaloids from Ayahuasca matrix plants, harmine (HRE) and N,N-dimethyltryptamine (DMT), were also isolated and evaluated. An untargeted metabolomics approach was developed to explore the chemical composition of samples with neuroprotective activity. Ultra-Performance Liquid Chromatography coupled to Electrospray Ionisation and Time-of-Flight (UPLC-ESI-TOF) metabolome data was treated and further analysed using multivariate statistical analyses (MSA): principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). The metabolites were dereplicated using the Dictionary of Natural Products and an in house database. The main alkaloids were also quantified by UPLC-MS/MS. RESULTS: The samples did not cause cytotoxicity in vitro and three of samples intensely increased cell viability at T1. The crude extracts, alkaloid fractions and HRE demonstrated remarkable neuroprotective effect at T2 while the hydroalcoholic fractions demonstrated this neuroprotective effect at T1 and T2. Several compounds from different classes, such as ß-carbolines and monoterpene indole alkaloids (MIAs) were revealed correlated with this property by MSA. Additionally, a total of 2419 compounds were detected in both ionisation modes. HRE showed potent neuroprotective action at 72 h, but it was not among the metabolites positively correlated with the most efficacious neuroprotective profile at either time (T1 and T2). Furthermore, DMT was statistically important to differentiate the dataset (VIP value > 1), although it did not exhibit sufficient neuroprotective activity by in vitro assay, neither a positive correlation with T1 and T2 neuroprotective profile, which corroborated the MSA results. CONCLUSION: The lower doses of the active samples stimulated neuronal cell proliferation and/or displayed the most efficacious neuroprotection profile, namely by preventing neuronal damage and improving cell viability against 6-OHDA-induced toxicity. Intriguingly, the hydroalcoholic fractions exhibited enhanced neuroprotective effects when compared to other samples and isolated alkaloids. This finding corroborates the significance of a holistic approach. The results demonstrate that Ayahuasca and its base plants have potential applicability for PD treatment and to prevent its progression differently from current drugs to treat PD.
Assuntos
Antiparkinsonianos/farmacologia , Banisteriopsis/química , Metabolômica , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Psychotria/química , Antiparkinsonianos/isolamento & purificação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Etnofarmacologia , Humanos , Análise dos Mínimos Quadrados , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/isolamento & purificação , Oxidopamina/toxicidade , Extratos Vegetais/isolamento & purificação , Polissacarídeos , Análise de Componente Principal , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em TandemRESUMO
In clinical, Psychotria serpens L. was often substitute for Caulis trachelospermi to treat cancer in China. Meanwhile, EtOAc and n-BuOH fractions of MeOH extract of P. serpens L. show power activity against H460, HepG2, Hela, and PC9/GR cell lines, and no toxic effects against normal 16HBE cell lines. In our ongoing search for bioactive novel compounds from Chinese material medica, one new type of glycosylsphingolipids Psychotramide (1a-1c) were isolated from P. serpens L., and their structures were identified through spectroscopic techniques including NMR (1D and 2D) and MS (LC-MS, and GC-MS).
Assuntos
Glicoesfingolipídeos/isolamento & purificação , Psychotria/química , Linhagem Celular , China , Cromatografia Gasosa-Espectrometria de Massas , Glicoesfingolipídeos/química , Glicoesfingolipídeos/farmacologia , Humanos , Medicina Tradicional Chinesa , Estrutura Molecular , Análise EspectralRESUMO
PURPOSE: Ayahuasca is a traditional Amazonian medicine that is currently being researched for its potential in treating a variety of mental disorders. This article reports on exploratory qualitative research relating to participant experiences with ceremonial ayahuasca drinking and conventional treatment for eating disorders (EDs). It also explores the potential for ayahuasca as an adjunctive ED treatment. METHODS: Thirteen individuals previously diagnosed with an ED participated in a semi-structured interview contrasting their experiences with conventional ED treatment with experiences from ceremonial ayahuasca. The interviews were analyzed using thematic analysis. RESULTS: Participant reports were organized with key themes including that ayahuasca: led to rapid reductions in ED thoughts and symptoms; allowed for the healing of the perceived root of the ED; helped to process painful feelings and memories; supported the internalization of greater self-love and self-acceptance; and catalyzed spiritual elements of healing. CONCLUSIONS: The results suggest that ayahuasca may have potential as a valuable therapeutic tool, and further research-including carefully controlled clinical trials-is warranted. LEVEL OF EVIDENCE: Level V, qualitative descriptive study.
Assuntos
Banisteriopsis , Comportamento Ritualístico , Transtornos da Alimentação e da Ingestão de Alimentos/terapia , Psychotria , Adulto , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Adulto JovemRESUMO
Species from Psychotria are used in folk medicine against inflammatory diseases, respiratory disturbances, and anti-hallucinogenic. In the present study, the compound vincosamide (PL-1) was identified for the first time in methanolic extract of the Psychotria leiocarpa (ME-PL) leaves, as well as the anti-inflammatory and anticholinesteric effects in rodents and molecular docking simulations. The fractionation of the chloroform fraction (CF-PL) through chromatographic methods afforded the known compound PL-1. The anti-inflammatory activity of the ME-PL (30, 100, and 300 mg/kg) and PL-1 (3, 30, and 100 mg/kg) was analyzed using experimental models: paw edema, pleurisy, and mechanical and thermal hyperalgesia induced by carrageenan. The anticholinesterase activity of the ME-PL (30 and 100 mg/kg) and PL-1 (30 mg/kg) was showed by acetylcholinesterase (AChE) inhibitory in brain structures. The molecular docking simulations were performed using Molegro Virtual Docker v6.0. Overall, the results indicated that ME-PL and PL-1 demonstrated an anti-edematogenic effect in Cg-induced paw edema, leukocyte migration in the pleurisy model, and significantly reduced mechanical hyperalgesia, cold response to acetone in mice. The samples exhibited maximal inhibition of enzyme acetylcholinesterase (AChE) in the frontal cortex. The molecular coupling of PL-1 with the AChE showed significant interactions with the catalytic and peripheral site, corroborating the activity presented in the inhibition assay. The acute administration of ME-PL did not cause signs of toxicity in the treated animals. The results showed that P. leiocarpa inhibited AChE and anti-inflammatory activity, and alkaloid vincosamide could be responsible, at least in part, for the observed effects, supporting the popular use of this genus.
Assuntos
Acetilcolinesterase/efeitos dos fármacos , Alcaloides Indólicos/farmacologia , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Psychotria/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Edema/tratamento farmacológico , Hiperalgesia/tratamento farmacológico , Alcaloides Indólicos/uso terapêutico , Inflamação/induzido quimicamente , Camundongos , Simulação de Acoplamento Molecular , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Pleurisia/tratamento farmacológicoRESUMO
A standard protocol to develop type 1 diabetes in zebrafish is still uncertain due to unpredictable factors. In this study, an optimized protocol was developed and used to evaluate the anti-diabetic activity of Psychotria malayana leaf. The aims of this study were to develop a type 1 diabetic adult zebrafish model and to evaluate the anti-diabetic activity of the plant extract on the developed model. The ability of streptozotocin and alloxan at a different dose to elevate the blood glucose levels in zebrafish was evaluated. While the anti-diabetic activity of P. malayana aqueous extract was evaluated through analysis of blood glucose and LC-MS analysis fingerprinting. The results indicated that a single intraperitoneal injection of 300 mg/kg alloxan was the optimal dose to elevate the fasting blood glucose in zebrafish. Furthermore, the plant extract at 1, 2, and 3 g/kg significantly reduced blood glucose levels in the diabetic zebrafish. In addition, LC-MS-based fingerprinting indicated that 3 g/kg plant extract more effective than other doses. Phytosterols, sugar alcohols, sugar acid, free fatty acids, cyclitols, phenolics, and alkaloid were detected in the extract using GC-MS. In conclusion, P. malayana leaf aqueous extract showed anti-diabetic activity on the developed type 1 diabetic zebrafish model.
Assuntos
Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Psychotria/química , Peixe-Zebra/sangue , Animais , Hipoglicemiantes/química , Extratos Vegetais/química , Extratos Vegetais/farmacocinéticaRESUMO
A phytochemical study of leaves and twigs of Psychotria nuda resulted in 19 compounds, including five indole alkaloids, N,N,N-trimethyltryptamine, lyaloside, strictosamide, strictosidine, and 5α-carboxystrictosidine; two flavonolignans, cinchonain Ia and cinchonain Ib; an iridoid, roseoside; a sugar, lawsofructose; a coumarin, scopoletin; a diterpene, phytol; three triterpenes, pomolic acid, spinosic acid, and rotungenic acid; and five steroids, sitosterol, stigmasterol, campesterol, ß-sitosterol-3-O-ß-d-glucoside, and ß-stigmasterol-3-O-ß-d-glucoside. Some compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis and their ability to inhibit NO production by macrophages stimulated by lipopolysaccharide (LPS). The compounds pomolic acid, spinosic acid, strictosidine, and 5α-carboxystrictosidine displayed antimycobacterial activity with minimum inhibitory concentrations ranging from 7.1 to 19.2 µg/mL. These compounds showed promising inhibitory activity against NO production (IC50 3.22 to 25.5 µg/mL). 5α-carboxystrictosidine did not show cytotoxicity against macrophages RAW264.7 up to a concentration of 100 µg/mL. With the exception of strictosamide, this is the first report of the occurrence of these substances in P. nuda.
Assuntos
Alcaloides/análise , Antibacterianos/análise , Antioxidantes/análise , Psychotria/química , Triterpenos/análise , Alcaloides/farmacologia , Animais , Antibacterianos/farmacologia , Antioxidantes/farmacologia , Lipopolissacarídeos/efeitos adversos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Mycobacterium tuberculosis/efeitos dos fármacos , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Folhas de Planta/química , Células RAW 264.7 , Triterpenos/farmacologiaRESUMO
Ayahuasca is a beverage used in religious rituals of indigenous and nonindigenous groups, and its therapeutic potential has been investigated. Ayahuasca is obtained by decoction of the Banisteriopsis caapi that contains ß-carbolines (harmine, harmaline, and tetrahydroharmine) plus Psychotria viridis that contains N,N-dimethyltryptamine. Although plants used in folk medicine are recognized as safe, many of them have genotoxic potential. The Salmonella/microsome assay is usually the first line of the mutagenicity evaluation of products intended for therapeutic use. Our objective was to evaluate the mutagenicity of ayahuasca beverage and their constituents using the Salmonella/microsome assay with TA98 and TA100. We analyzed two ayahuasca samples, and also beverage samples prepared each individual plant P. viridis and B. caapi. Harmine and harmaline were also tested. All beverage samples were chemically characterized and both ayahuasca samples could be considered representative of the beverages consumed in religious rituals. Both ayahuasca samples were mutagenic for TA98 and TA100 with and without S9, with similar potencies. The beverage obtained from P. viridis was not mutagenic, and beverage obtained from B. caapi was mutagenic for TA98 with and without S9. Harmine was nonmutagenic and harmaline was mutagenic only for TA98 without S9. Harmaline fully explain the mutagenicity observed with TA98 without S9 of both ayahuasca samples and the B. caapi beverage samples. We conclude that the ayahuasca samples are mutagenic and this effect is partially explained by harmaline, one of the ß-carbolines present in the beverage. Other mutagenic compounds seem to be present and need to be further investigated. Environ. Mol. Mutagen. 60:269-276, 2019. © 2018 Wiley Periodicals, Inc.