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J Nat Prod ; 84(3): 790-796, 2021 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-33371682


Metabolomics analysis detected tambjamine alkaloids in aqueous and EtOAc extracts of the marine invertebrates Virididentula dentata, Tambja stegosauriformis, Tambja brasiliensis, and Roboastra ernsti. Among several tambjamines, the new amino acid derivatives tambjamines M-O (17-19) were identified by Marfey's advanced analysis, UPLC-MS/MS analyses, and total synthesis. The tambjamine diversity increased from the bryozoan V. dentata to its nudibranch predators T. stegosauriformis and T. brasiliensis and attained a higher diversity in R. ernsti, the nudibranch that preys upon T. stegosauriformis and T. brasiliensis. The total tambjamine content also increases among the trophic levels, probably due to biomagnification. Tambjamines A (1), C (3), and D (4) are the major metabolites in the tissues of V. dentata, T. stegosauriformis, T. brasiliensis, and R. ernsti and are likely the main chemical defenses of these marine invertebrates.

Alcaloides/isolamento & purificação , Gastrópodes/química , Pirróis/isolamento & purificação , Animais , Organismos Aquáticos/química , Brasil , Cromatografia Líquida de Alta Pressão , Cadeia Alimentar , Metabolômica , Estrutura Molecular , Espectrometria de Massas em Tandem
J Ethnopharmacol ; 255: 112743, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32171895


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.

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 Tandem
J Ethnopharmacol ; 253: 112655, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32045681


ETHNOPHARMACOLOGICAL RELEVANCE: Species Cissus gongylodes has been used in the traditional medicine in South America and India for the treatment of urolithiasis, biliary and inflammatory problems without any scientific evidence. AIM OF THE STUDY: This work was developed to investigate for the first time the anti-inflammatory and anti-urolithiatic activities of leaf decoction of C. gongylodes. MATERIALS AND METHODS: Decoction was subjected to anti-inflammatory evaluation by the in vivo assay of ear oedema and quantification of the main mediators of inflammation PGE2 and LTB4, and the cytokine TNF-α. The decoction's anti-urolithiatic activity was determined by different in vitro assays to evaluate the inhibition and dissolution of the most prevalent types of kidney stones: calcium oxalate (CaOx) and struvite. Diffusion in gel technique and fresh urine of a patient with renal stone were used to investigate the inhibition and dissolution of CaOx, respectively, and the single diffusion gel growth technique was used to evaluate the inhibition and dissolution of struvite crystals. The decoction was chemically characterized by UHPLC-ESI-HRMS analysis. RESULTS: Decoction showed in vivo anti-inflammatory activity by potent decreasing the level of both the main mediators of inflammation and dose-dependent in vitro anti-urolithiatic action by inhibition and dissolution of both type of crystals, CaOx and struvite. CONCLUSIONS: Results obtained corroborate the reports of the traditional use of the decoction of Cissus gongylodes. Besides, it showed multi-target mechanisms actions, inhibition of the main inflammatory pathways, and inhibition/dissolution of the most prevalent types of crystals on urolithiasis. These actions make the decoction a promissory source to the development of new and more efficient drugs.

Anti-Inflamatórios/uso terapêutico , Cissus , Edema/tratamento farmacológico , Cálculos Renais/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Oxalato de Cálcio/química , Óleo de Cróton , Cristalização , Dinoprostona/metabolismo , Edema/induzido quimicamente , Edema/metabolismo , Humanos , Cálculos Renais/química , Leucotrieno B4/metabolismo , Masculino , Camundongos , Extratos Vegetais/química , Folhas de Planta , Estruvita/química , Fator de Necrose Tumoral alfa/metabolismo
Nat Chem ; 10(9): 938-945, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30061613


Studies of secondary metabolites (natural products) that cover their isolation, chemical synthesis and bioactivity investigation present myriad opportunities for discovery. For example, the isolation of novel secondary metabolites can inspire advances in chemical synthesis strategies to achieve their practical preparation for biological evaluation. In the process, chemical synthesis can also provide unambiguous structural characterization of the natural products. Although the isolation, chemical synthesis and bioactivity studies of natural products are mutually beneficial, they are often conducted independently. Here, we demonstrate the benefits of a collaborative study of the phomactins, diterpenoid fungal metabolites that serve as antagonists of the platelet activating factor receptor. Our isolation of novel phomactins has spurred the development of a bioinspired, unified approach that achieves the total syntheses of six congeners. We also demonstrate in vitro the beneficial effects of several phomactins in suppressing the rate of repopulation of tumour cells following gamma radiation therapy.

Produtos Biológicos/síntese química , Terpenos/química , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Fungos/química , Fungos/metabolismo , Raios gama , Humanos , Concentração Inibidora 50 , Glicoproteínas da Membrana de Plaquetas/antagonistas & inibidores , Glicoproteínas da Membrana de Plaquetas/metabolismo , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores Acoplados a Proteínas G/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade , Terpenos/isolamento & purificação , Terpenos/farmacologia
J Nat Prod ; 80(2): 235-240, 2017 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-28191971


Herein we report the isolation and spectroscopic identification of fistularin-3 (1), 11-hydroxyaerothionin (2), and verongidoic acid (3), as well as the UPLC-HRMS detection of aerothionin (4), homopurpuroceratic acid B (5), purealidin L (6), and aplysinamisine II (7), from cultures of the marine bacterium Pseudovibrio denitrificans Ab134, isolated from tissues of the marine sponge Arenosclera brasiliensis. These results unambiguously demonstrate for the first time that bromotyrosine-derived alkaloids that were previously isolated only from Verongida sponges can be biosynthesized by a marine bacterium.

Alcaloides/química , Bactérias/química , Poríferos/química , Tirosina/análogos & derivados , Animais , Brasil , Isoxazóis/química , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Oceanos e Mares , Tirosina/química