A coffee enriched with guarana, selenium, and l-carnitine (GSC) has nutrigenomic effects on oxi-inflammatory markers of relapsing-remitting multiple sclerosis patients: A pilot study.

Relapsing-remitting multiple sclerosis (RRMS) is the most common clinical course of multiple sclerosis (MS), characterized by a chronic inflammatory state and elevated levels of oxidative markers. Food supplements with potential anti-inflammatory, antioxidant and neuroprotective effects have been tested as possible adjuvants in the treatment of MS. In this sense, this pilot study was carried out with the aim of verifying whether a minimum daily dose of a guarana, selenium and l-carnitine (GSC) based multi supplement, mixed in cappuccino-type coffee, administered for 12 weeks to 28 patients with RRMS could differentially modulate oxidative blood markers (lipoperoxidation, protein carbonylation and DNA oxidation) and inflammatory blood markers (protein levels of cytokines IL-1ß, IL-6, TNF-α, IFN-γ, IL-10, gene expression of these cytokines, and NLRP3 and CASP-1 molecules, and C-reactive protein levels). The results indicate that a low concentration of GSC is capable of decreasing the plasma levels of oxidized DNA and pro-inflammatory cytokines of RRMS patients. The results support further research into the action of GSC on clinical symptoms, not only in patients with MS, but also with other neurological conditions.

Amazon-derived nutraceuticals: Promises to mitigate chronic inflammatory states and neuroinflammation.

Nutraceuticals have been the focus of numerous research in recent years and accumulating data support their use for promoting some health benefits. Several nutraceuticals have been widely studied as supplements due to their functional properties ameliorating symptoms associated with neurological disorders, such as oxidative stress and chronic inflammatory states. This seems to be the case of some fruits and seeds from the Amazon Biome consumed since the pre-Columbian period that could have potential beneficial impact on the human nervous system. The beneficial activities of these food sources are possibly related to a large number of bioactive molecules including polyphenols, carotenoids, unsaturated fatty acids, vitamins, and trace elements. In this context, this review compiled the research on six Amazonian fruits and seeds species and some of the major nutraceuticals found in their composition, presenting brief mechanisms related to their protagonist action in improving inflammatory responses and neuroinflammation.

Chlorpyrifos pesticide promotes oxidative stress and increases inflammatory states in BV-2 microglial cells: A role in neuroinflammation.

The exposure to environmental stressors, such as organophosphate (OP) pesticides, has been associated with the development of neurodegenerative diseases. Chlorpyrifos (CPF) is the worldwide most used OP pesticide and one of the most hazardous pesticides as it can cross the blood-brain barrier. Since studies evaluating the effects of CPF on brain immune cells are scarce, this research investigated the oxidative and inflammatory responses of CPF exposure in murine microglial cells. BV-2 cells were exposed to different concentrations of CPF pesticide (0.3-300 µM). CPF induced activation of microglial cells, confirmed by Iba-1 and CD11b marking, and promoted microglial proliferation and cell cycle arrest at S phase. Moreover, CPF exposure increased oxidative stress production (NO, MDA, and O2∙), and upregulated pro-inflammatory cytokines (IL-1ß and NLRP3) genes expression in BV-2 cells. Overall, data showed that CPF exposure, at the lowest concentrations, acted by promoting pro-oxidative and pro-inflammatory states in microglial cells. These results provide important information on the potential role of microglial activation in CPF-induced neuroinflammation and add to the expanding knowledge on the neurotoxicity of OP.

Tucumã (Astrocaryum aculeatum) Prevents Oxidative and DNA Damage to Retinal Pigment Epithelium Cells.

Eye diseases have a negative impact on the eyesight quality of the world population. The age-related macular degeneration (AMD) draws special attention since it is a chronic disorder characterized by oxidative and inflammatory damage to the retinal epithelial pigment, which triggers progressive vision loss. In the Brazilian Amazon, Astrocaryum aculeatum is an Amazonian fruit (Tucumã) used by riverside communities in traditional medicine to treat a number of ailments. These communities have recently shown to have increased longevity and reduced prevalence of age-related morbidity. Thus, the aim of this research was to chemically characterize and analyze the in vitro antioxidant effect and molecular damage prevention of the Tucumã ethanolic extract in retinal pigment epithelium (RPE) cells in a model for AMD. The extract was chemically characterized by ultra-high-performance liquid chromatography (HPLC) coupled with diode-array detection and mass spectrophotometry (HPLC-DAD-MS). In vitro protocols were performed, and the cytopreventive effect of Tucumã on RPE cells exposed to high concentrations of superoxide anion, an oxidant and genotoxic molecule, as well as the effect of Tucumã extract on oxidative and molecular makers were assessed. Biochemical and flow cytometry analyses were conducted in these protocols. The extract presents high concentrations of caffeic acid, gallic acid, catechin, luteolin, quercetin, and rutin. Treatment did not show cytotoxic effects in cells treated only with extract at 50 µg/mL. In fact, it improved cell viability and was able to prevent necrosis and apoptosis, and oxidative and molecular damage was significantly reduced. In summary, Tucumã is an important Amazon fruit, which seems to contribute significantly to improve human health conditions, as our findings suggest that its extract has a relevant chemical matrix rich in antioxidant molecules, and its consumption could improve eye health and contribute to prevention against oxidative stress through cytoprevention, reactive oxygen species reduction, and maintenance of DNA integrity in retinal pigment epithelium (RPE) cells.

Caffeinated beverages contribute to a more efficient inflammatory response: Evidence from human and earthworm immune cells.

The role of caffeinated beverages on efficiency of acute inflammatory responses is not yet fully understood. This study analyzed the effect of five hot water extracts, coffee (CO), black/green tea (BT/GT), yerba mate (YM), and guarana (GU) on inflammatory modulation of non-activated human peripheral blood mononuclear cells (PBMCs), yeast-activated human neutrophils, and granulocytic coelomocytes from Eisenia fetida earthworm. Based on preliminary tests, a concentration of 10 µg/mL was chosen for subsequent assays, as at this concentration, the extracts exhibited antioxidant, genoprotective, and non-cytotoxic properties. Immunoassays using 24-h PBMC supernatant showed that all extracts decreased levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, and IFN-γ), and increased levels of the anti-inflammatory cytokine, IL-10. Further, these extracts induced overexpression of cytokine genes in 24-h cultures. These results suggest that an increase in the levels of mRNAs and/or inactive cytokines in the cytoplasm improves the "immune cytokine response. Analysis of the yeast encapsulation processes, and production of human neutrophils and coelomocyte extracellular DNA traps suggests that extracts also improve the immune response in humans and earthworms. However, for E. fetida, the intensity of these results varied from extract. Overall, our results suggest that caffeinated beverages may improve an organism's efficiency against acute inflammatory processes.

Immunomodulatory effect of mancozeb, chlorothalonil, and thiophanate methyl pesticides on macrophage cells.

Mancozeb (MZ), chlorothalonil (CT), and thiophanate methyl (TM) are pesticides commonly used in agriculture due to their efficacy, low acute toxicity to mammals, and short environmental persistence. Although the toxic effects of these pesticides have been previously reported, studies regarding their influence on the immune system are limited. As such, this study focused on the immunomodulatory effect of MZ, CT, and TM pesticides on macrophage cells. RAW 264.7 cells were exposed to a range of concentrations (0.1-100 µg/mL) of these pesticides. CT exposure promoted an increase in reactive oxygen species (ROS) and nitric oxide (NO) levels. The MTT and ds-DNA assay results demonstrated that MZ, CT, and TM exposure induced macrophage proliferation. Moreover, MZ, CT, and TM promoted cell cycle arrest at S phase, strongly suggesting macrophage proliferation. The levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, and IFN-γ) and caspases (caspase 1, 3, and 8) in macrophages exposed to MZ, CT, and TM pesticides increased, whereas the anti-inflammatory cytokine levels decreased. These results suggest that MZ, CT, and TM exert an immunomodulatory effect on the immune system, inducing macrophage activation and enhancing the inflammatory response.

A chemical compound based on methylxanthine-polyphenols lowers nitric oxide levels and increases post-thaw human sperm viability.

We produced a new chemical compound based on methylxanthines and polyphenols (CCMP) present in the chemical matrix of guaraná (Paullinia cupana), a seed extract with antioxidant properties. After supplementation with the standard extract of resveratrol, a well documented antioxidant found in other plant sources, we investigated whether this resveratrol-enriched compound could improve sperm viability and modulate differentially reactive oxygen species (ROS) and nitric oxide (NO) levels in thawed sperm. Sperm samples obtained from healthy young donors were treated with different concentrations of guaraná extract (0.1, 1, 5 or 10 mg/ml) and cells were frozen at -80°C for 24 h. In addition, the potential protective effects of guaraná treatment on sperm treated with pro-oxidant compound (200 µM hydrogen peroxide, H2O2) were assessed. Samples were also exposed to three concentrations of CCMP before being frozen in liquid nitrogen (-196°C) or in an ultrafreezer (-80°C) for 24 h, and both pre-freezing and post-thaw measurements of viability and oxidative stress were performed. Guaraná supplementation at 10 mg/ml significantly increased post-thaw viability and decreased oxidative metabolism of the sperm. Moreover, selected concentrations of CCMP improved viability and oxidative metabolism in sperm samples pre-freezing. Furthermore, CCMP showed cryoprotective activity by increasing viability and decreasing oxidative stress in post-thaw samples. In summary, these findings suggested that CCMP supplementation acts as a cryoprotectant to modulate ROS and NO levels in thawed sperm. CCMP could be used to enhance sperm quality and reproductive success.

Canabinoides sintéticos: drogas de abuso emergentes / Synthetic cannabinoids: emerging drugs of abuse

CONTEXTO: A Cannabis sativa (cannabis, maconha, marijuana) é uma droga de abuso com efeitos psicoativos e potencial terapêutico bastante conhecidos. Um grande número de canabinoides foi sintetizado na tentativa de excluir ou minimizar os efeitos psicotrópicos e mantendo as aplicações terapêuticas. Os canabinoides sintéticos representam o mais recente avanço das designer drugs. OBJETIVOS: Este trabalho busca trazer informações sobre a utilização de canabinoides sintéticos como drogas de abuso emergentes, principalmente sob a forma de spice ou herbal blends. MÉTODOS: Foi realizada uma pesquisa bibliográfica na base de dados PubMed utilizando os descritores de assunto "synthetic cannabinoids", "spice", "legal highs", "herbal blends", "psychosis cannabis" e suas combinações. RESULTADOS: Foram encontrados canabinoides sintéticos nos produtos Spice, confirmando que os incensos herbais realmente surgiram como drogas de abuso emergentes. CONCLUSÃO: Não está claro se a utilização de canabinoides sintéticos e de Spice é uma moda passageira ou se irá se estabelecer em nossa sociedade. No entanto, o fenômeno das designer drugs, especialmente canabinoides sintéticos, representa um desafio presente para o sistemas de saúde no mundo globalizado, tornando-se necessária a pesquisa clínica e forense desses produtos.

BACKGROUND: Cannabis sativa (cannabis, marijuana) is a drug of abuse with well known psychoactive effects and therapeutic potential. A large number of cannabinoids chemically similar to Δ9-THC, the main active metabolite of marijuana, were synthesized in an attempt to exclude or minimize the psychotropic effects, maintaining the therapeutic potential. OBJECTIVES: The aim of this work was to review of the use of synthetic cannabinoids as emerging drugs of abuse, especially in the form of spice or herbal blends. METHODS: A bibliographic search was performed in PubMed employing the terms "synthetic cannabinoids", "spice", "legal highs", "herbal blends", "psychosis cannabis" and cross references. RESULTS: A number of synthetic cannabinoids can be found in Spice products, confirming that herbal incense emerged as new drugs of abuse. DISCUSSION: It is unclear whether the use of synthetic cannabinoids and Spice is a fad or will be established as common practice in our society. However, the phenomenon of designer drugs, especially synthetic cannabinoids, will remain a challenge to health authorities in the globalized world, requiring additional clinical and forensic research.