Phytoestrogen agathisflavone ameliorates neuroinflammation-induced by LPS and IL-1β and protects neurons in cocultures of glia/neurons

Inflammation and oxidative stress are common aspects of most neurodegenerative diseases in the central nervous system. In this context, microglia and astrocytes are central to mediating the balance between neuroprotective and neurodestructive mechanisms. Flavonoids have potent anti-inflammatory and antioxidant properties. Here, we have examined the anti-inflammatory and neuroprotective potential of the flavonoid agathisflavone (FAB), which is derived from the Brazilian plant Poincianella pyramidalis, in in vitro models of neuroinflammation. Cocultures of neurons/glial cells were exposed to lipopolysaccharide (LPS, 1 µg/mL) or interleukin (IL)-1β (10 ng/mL) for 24 h and treated with FAB (0.1 and 1 µM, 24 h). FAB displayed a significant neuroprotective effect, as measured by nitric oxide (NO) production, Fluoro-Jade B (FJ-B) staining, and immunocytochemistry (ICC) for the neuronal marker β-tubulin and the cell death marker caspase-3, preserving neuronal soma and increasing neurite outgrowth. FAB significantly decreased the LPS-induced microglial proliferation, identified by ICC for Iba-1/bromodeoxyuridine (BrdU) and CD68 (microglia M1 profile marker). In contrast, FAB had no apparent effect on astrocytes, as determined by ICC for glial fibrillary acidic protein (GFAP). Furthermore, FAB protected against the cytodestructive and proinflammatory effects of IL-1β, a key cytokine that is released by activated microglia and astrocytes, and ICC showed that combined treatment of FAB with α and β estrogen receptor antagonists did not affect NF-κB expression. In addition, qPCR analysis demonstrated that FAB decreased the expression of proinflammatory molecules TNF-α, IL-1β, and connexins CCL5 and CCL2, as well as increased the expression of the regulatory molecule IL-10. Together, these findings indicate that FAB has a significant neuroprotective and anti-inflammatory effect in vitro, which may be considered as an adjuvant for the treatment of neurodegenerative diseases

Neuroimmunomodulatory and neuroprotective effects of the flavonoid apigenin in in vitro models of neuroinflammation associated with Alzheimer's disease

Neurodegenerative disorders (ND) are characterized by the progressive and irreversible loss of neurons. Alzheimer’s Disease (AD) is the most incident age-related ND, in which the presence of a chronic inflammatory compound seems to be related to its pathogenesis. Different stimuli in the central nervous system (CNS) can induce activation, proliferation, and changes in phenotype and glial function, which can be modulated by anti-inflammatory agents. Apigenin (4,5,7–trihydroxyflavone) is a flavonoid found in abundance in many fruits and vegetables, that has shown important effects upon controlling the inflammatory response. This study evaluated the neuroprotective and neuroimmunomodulatory potential of apigenin using in vitro models of neuroinflammation associated with AD. Co-cultures of neurons and glial cells were obtained from the cortex of newborn and embryonic Wistar rats. After 26 days in vitro, cultures were exposed to lipopolysaccharide (LPS; 1 μg/ml), or IL-1β (10 ng/ml) for 24 h, or to Aβ oligomers (500 nM) for 4 h, and then treated with apigenin (1 μM) for further 24 h. It was observed that the treatment with apigenin preserved neurons and astrocytes integrity, determined by Rosenfeld’s staining and immunocytochemistry for β-tubulin III and GFAP, respectively. Moreover, it was observed by Fluoro-Jade-B and caspase-3 immunostaining that apigenin was not neurotoxic and has a neuroprotective effect against inflammatory damage. Additionally, apigenin reduced microglial activation, characterized by inhibition of proliferation (BrdU+ cells) and modulation of microglia morphology (Iba-1 + cells), and decreased the expression of the M1 inflammatory marker CD68. Moreover, as determined by RT-qPCR, inflammatory stimuli induced by IL-1β increased the mRNA expression of IL-6, IL-1β, and CCL5, and decreased the mRNA expression of IL-10. Contrary, after treatment with apigenin in inflammatory stimuli (IL-1β or LPS) there was a modulation of the mRNA expression of inflammatory cytokines, and reduced expression of OX42, IL-6 and gp130. Moreover, apigenin alone and after an inflammatory stimulus with IL-1β also induced the increase in the expression of brain-derived neurotrophic factor (BDNF), an effect that may be associated with anti-inflammatory and neuroprotective effects. Together these data demonstrate that apigenin presents neuroprotective and anti-inflammatory effects in vitro and might represent an important neuroimmunomodulatory agent for the treatment of neurodegenerative conditions

The flavonoid agathisflavone modulates the microglial neuroinflammatory response and enhances remyelination

Myelin loss is the hallmark of the demyelinating disease multiple sclerosis (MS) and plays a significant role in multiple neurodegenerative diseases. A common factor in all neuropathologies is the central role of microglia, the intrinsic immune cells of the central nervous system (CNS). Microglia are activated in pathology and can have both pro- and anti-inflammatory functions. Here, we examined the effects of the flavonoid agathisflavone on microglia and remyelination in the cerebellar slice model following lysolecithin induced demyelination. Notably, agathisflavone enhances remyelination and alters microglial activation state, as determined by their morphology and cytokine profile. Furthermore, these effects of agathisflavone on remyelination and microglial activation were inhibited by blockade of estrogen receptor α. Thus, our results identify agathisflavone as a novel compound that may act via ER to regulate microglial activation and enhance remyelination and repair

Valor nutricional do mel e pólen de abelhas sem ferrão da região Amazônica

Avaliou-se os constituintes nutricionais de amostras do mel e pólen das espécies Melipona seminigra merrillae (jandaíra), Melipona compressipes manaosensis (jupará), Melipona rufiventris paraensis (uruçu boca de ralo), provenientes do meliponário da Fazenda Poranga no município de Itacoatiara - AM e Meliponário Abelhudo em Manaus - AM. Os resultados demonstraram o potencial do mel como fonte de energia, particularmente a M. rufiventris com 305,3±2,4 kcal em 100g. O pólen da espécie M. compressipes apresentou a maior concentração de proteína 15,7±0,0% e energia 309,8±0,8 kcal. Tais constatações sugerem a implementação de novos estudos visando à incorporação destes produtos na dieta dos amazônidas, possibilitando uma nova fonte alternativa de alimento potencialmente nutritivo e saudável.<br>We evaluated the nutricional constituent of honey and pollen samples of the Melipona species seminigra merrillae (jandaíra) Melipona compressipes manaosensis (jupará), Melipona rufiventris paraensis (uruçu boca de ralo), proceeding from the Poranga Honey Farm in Itacoatiara - AM, and Meliponário Abelhudo in Manaus, AM. The results demonstrated the potencial of honey as a source of energy, particularly the kcal M. rufiventris with 305.3±2.4 kcal in 100g. The compressis pollen of species presented the highest concentration of protein 15.7±0.0 % and energy 309.8±0.8 kcal. Thus we suggest the implementation of new studies aiming at the incorporation of these products in the diet of the Amazon population, making possible a new potentially nutritional and alternative healthful food source

Levantamento da flora apícola em Santa Luzia do Paruá, Sudoeste da Amazônia, Maranhão Survey of bee flora in Santa Luzia do Paruá, Southwest Amazonia, Maranhão

Foi realizado o levantamento das plantas visitadas por Apis mellifera L. através de análise polínica no município de Santa Luzia do Paruá, Maranhão, localizado a noroeste do Estado, em região amazônica. A temperatura média anual varia entre 26 °C e 27 °C, com umidade relativa do ar anual entre 79 a 82% e precipitação pluviométrica entre 2000 a 2400 mm anuais. O estudo foi conduzido entre agosto de 2005 e julho de 2006 em três apiários da região, com coletas mensais de mel, pólen e plantas, que foram submetidas ao método de acetólise. Os tipos polínicos das amostras de mel foram identificados e contados para a determinação da freqüência relativa média. Nas amostras de pólen foi realizada apenas a identificação dos tipos polínicos por meio da comparação com os polens das plantas (botões florais) depositados em coleção de referência. As principais famílias utilizadas por A. mellifera foram Amaranthaceae, Arecaceae, Asteraceae, Urticaceae, Euphorbiaceae, Lamiaceae, Fabaceae-Mimosoideae, Flacourtiaceae, Myrtaceae, Poaceae e Rubiaceae. Em amostras de mel, no período chuvoso destacaram-se os tipos polínicos de Mimosa pudica, Borreria e um tipo indeterminado da família Arecaceae. No período de safra foram representativos Hyptis e um tipo indeterminado de Asteraceae. Os tipos polínicos mais constantes nas amostras de pólen foram Euterpe oleracea, Asteraceae tipo 1, Mimosa pudica e Borreria.<br>The plant species visited by Apis mellifera L. were surveyed by pollen analysis in Santa Luzia do Paruá municipality, located in northwestern Maranhão state. Natural vegetation is Amazon rainforest, mean annual temperature varies between 26°C and 27°C, relative air humidity between 79 and 82%, and total rainfall between 2000 and 2400 mm. This study was conducted from August 2005 to July 2006 in three apiaries of the region, with monthly sampling of honey, pollen and plants. The samples were analyzed by the acetolysis method. The pollen types were identified and counted in honey samples to determine mean frequency of the three apiaries. In the pollen samples, pollen types were identified by comparison with the pollen of plants (flower buds) deposited in the reference collection. The main plant families used as floral resource by A. mellifera are Amaranthaceae, Arecaceae, Asteraceae, Urticaceae, Euphorbiaceae, Lamiaceae, Fabaceae-Mimosoideae, Flacourtiaceae, Myrtaceae, Poaceae and Rubiaceae. In the honey samples, the pollen types of Mimosa pudica, Borreria and members of the Arecaceae family were most important during the rainy season. At harvest time (transition between rainy and dry season), Hyptis, Borreria, and an undetermined pollen type of the Asteraceae family were most important. The pollen types that show major constancy in the sample pollen were Euterpe oleracea, Asteraceae type 1, Mimosa pudica and Borreria