Modulating Effects of Arabinogalactans from Plant Gum Exudates on Human Complement System.

Gum arabic and cashew nut tree gum exudate polysaccharide (CNTG) are plant polysaccharides composed of galactose and arabinose known as arabinogalactans (AGs). Although these fractions are used in food and pharmaceutical industry, cases of allergic reactions were described in clinical reports. As AGs were reported as modulators of the classical (CP) and alternative pathways (AP) of complement system (CS), in the present work, we investigate whether gum arabic and CNTG have an effect on both CS pathways. The complement fixation tests were performed with (CP-30 and AP-30) and without pre-incubation (CP-0 and AP-0). For CP-30, CNTG and gum arabic (833 µg/ml) showed a reduction of 28.0% (P = 0.000174) and 48.5% (P = 0.000143), respectively, on CP-induced haemolysis. However, no effect was observed for CP-0 in the CP-induced haemolysis. For AP-30, both CNTG and gum arabic (833 µg/ml) showed 87% reduction on the CP-induced haemolysis, with IC50 values of 100 and 7 µg/ml, respectively. For AP-0, a reduction of 11.3% for gum arabic and no effect for the CNTG on the CP-induced haemolysis were observed. These results suggested that gum arabic and CNTG could be acting as activators of the CS. Thus, this effect on the CS, especially on the AP, which accounts for up to 80-90% of total CS activation, indicates that both fractions may be harmful because of their potential pro-inflammatory action. Considering that CS activation induces inflammatory response, further studies confirming this immunomodulatory effect of these fractions are required to insure their safe use.

Pectinas de plantas medicinais: características estruturais e atividades imunomoduladoras / Pectins of medicinal plants: structural characteristics and immunomodulatory activities

RESUMO As plantas medicinais apresentam várias propriedades terapêuticas, as quais estão relacionadas com a presença de compostos bioativos. Dentre os compostos, destacam-se as pectinas, que compreendem um grupo de polissacarídeos ácidos de relevante importância medicinal e nutracêutica. As pectinas são formadas por unidades de ácido galacturônico, unidas por ligação do tipo α-(1→4), sendo classificadas em homogalacturonanas e ramnogalacturonanas tipo I (RG-I) e tipo II (RG-II). Outros polissacarídeos constituídos por arabinose e/ou galactose têm sido isolados em associação com polissacarídeos pécticos, como as arabinogalactanas (AG) (tipo I e tipo II). As AG-II podem estar associadas a proteínas, denominadas de arabinogalactana-proteínas (AGPs). Inúmeros relatos demonstram que as pectinas, bem como as AG e AGPs, podem atuar como moduladores do sistema imunológico, sendo, por isso, consideradas modificadores da resposta biológica. A imunomodulação pode estar relacionada tanto com a atividade de macrófagos quanto com as vias do sistema complemento. Em geral, os polissacarídeos provocam um estímulo da atividade fagocitária; no aumento da produção de espécies reativas de oxigênio e da secreção de citocinas pró-inflamatórias. Em relação ao sistema complemento, os polissacarídeos podem modular tanto a via clássica como a via alternativa. A presente revisão tem como objetivo principal descrever os aspectos estruturais de pectinas e suas atividades biológicas relacionadas à modulação do sistema imune. Utilizando literatura específica, estão descritas informações de 29 espécies de plantas medicinais, que apresentam como constituintes pectinas, arabinogalactanas e/ou AGPs, correlacionando suas propriedades terapêuticas com as atividades biológicas associadas ao sistema imune. Na maioria dos casos descritos na literatura, é difícil determinar como as características estruturais específicas podem estar envolvidas na modulação da atividade de macrófagos. Porém, em relação à modulação da atividade do sistema complemento fica sugerido que a presença de estruturas tipo AG-II contribuiria mais significativamente para esta atividade. Entretanto, os possíveis mecanismos de modulação de pectinas, AGs e AGPs sobre a atividade de macrófagos e/ou sobre o sistema complemento ainda não estão totalmente esclarecidos, mesmo assim, estes polímeros podem ser considerados potenciais candidatos para estudos que visam ao desenvolvimento de novos agentes terapêuticos com propriedades moduladoras benéficas para o sistema imunológico.

ABSTRACT Medicinal plants have many therapeutic properties that are related to the presence of biologically active compounds. Pectins, a group of acid polysaccharides that have relevant medicinal and nutraceutical properties, are an example of such biological compounds. Pectins contain a main chain with galacturonic acid units that are α-(1→4) linked; they can be classified into homogalacturonans and type I and type II rhamnogalacturonans (RG-I and RG-II). Other polysaccharides containing arabinose, galactose, or both have been isolated in association with pectin-type polysaccharides are known as arabinogalactans (AGs, type I and type II). Arabinogalactan-proteins (AGPs) comprise AG-II associated with proteins. Several studies have reported that pectins, as well as AG and AGPs, can act as modulators of the immune system and can therefore be considered biological response modifiers. The immunomodulation is related to the activity of macrophages as on the complement system pathways. In general, polysaccharides cause stimulation of phagocytic activity, increase production of reactive oxygen species and secretion of pro-inflammatory cytokines. Polysaccharides can modulate the classical and alternative complement pathways. The aim of this review has to describe the structural aspects of pectins and their biological activities related to the modulation of the immune system. Using literature, we reported data of 29 medicinal plant species, which present as constituents pectins, arabinogalactan and/or AGPs, correlating their therapeutic properties with biological activities associated to the immune system. In most cases described in the literature, it is difficult to determine how the specific structural characteristics can be involved in modulation of macrophage activity. However, with respect to the modulation of the activity of the complement system is proposed that the presence of AG-II-type structures would contribute most significantly to this activity. The possible mechanisms of modulation of pectins, AGs and AGPs on macrophage activity and/or the complement system are not yet fully clear, even if, these polymers can be considered potential candidates for studies aimed at the development of new therapeutic agents with modulatory properties beneficial to the immune system.

Utilização de planejamento fatorial para a determinação da capacidade antioxidante e doseamento de flavonoides totais em Verbena minutiflora Briq. ex Moldenke (gervai) / The use of factorial design for determining the antioxidant capacity and dosing the total flavonoids in Verbena minutiflora Briq. Ex Moldenke (Gervai)

RESUMO Verbena minutiflora Briq. ex Moldenke (gervai) tem seu uso medicinal relatado popularmente para tratamento de doenças hepáticas, diarreia e outros problemas de saúde. Entretanto, pouco se conhece a respeito de seus componentes químicos e estudos que comprovem suas propriedades medicinais são escassos. O objetivo desse estudo foi avaliar a composição química dos extratos aquosos e etanólicos de flores de V. minutiflora e otimizar processos de obtenção de extratos com maiores capacidades antioxidantes e maiores concentrações de flavonoides. O método de extração foi desenhado por planejamento fatorial, onde as variáveis para a determinação da capacidade antioxidante foram: pH, extração líquida, método e tempo de extração. Para a determinação de flavonoides totais as variáveis avaliadas por planejamento fatorial foram: concentração de hexametilenotetramina, tipo de ácido, volume de ácido e tempo de aquecimento. Os resultados das análises químicas dos extratos mostraram: aminogrupos, taninos e ácidos fixos (extrato aquoso) aminogrupos, flavonoides, triterpenos, esteroides, alcaloides e cumarinas (extrado hidroetanólico). Os resultados dos planejamentos fatoriais mostraram que o melhor método de extração para a capacidade antioxidante foi o que usou vórtex, por 35 min, com água:etanol 50:50, com pH1, obtendo 0,1899± 5,8.10-3 mmol expressos em ácido ascórbico g-1 nos extratos de V. minutiflora. Enquanto, para as dosagens de flavonoides totais as variáveis significantes foram: tipo de ácido e volume de ácido. A melhor extração obtida foi: 6,748. 10-2± 2,085 10-3% expressos em quercetina. Os resultados mostraram que o planejamento fatorial é uma importante ferramenta para a otimização de extração de componentes químicos em produtos naturais.

ABSTRACT Verbena minutiflora Briq. ex Moldenke (gervai) has its popular use reported for liver disorders treatments, diarrhea, and other health problems. However, little is known about its chemical components and studies that proves its medicinal properties are rare. The aim of this study was to evaluate the chemical composition of aqueous and ethanolic extracts from flowers of V. minutiflora and to optimize processes to obtain extracts with higher antioxidant capacity and greater concentration of flavonoids. The methods of extraction were designed by factorial planning, where the variables to determine the antioxidant capacity were: pH; extraction liquid; method and extraction time. To determinate the total flavonoids the variables evaluated by factorial design were: concentration of hexamethylenetetramine; type of acid; volume of acid and warming time. The results of chemical analysis of the extracts showed: amino groups, tannins and fixed acids (aqueous extract) amino groups, flavonoids, triterpenes, steroids, alkaloids and coumarins (hydroalcoholic extract). The factorial designs results showed that the best extraction method for the antioxidant capacity was the one that uses vortex, for 35 min, with water: ethanol 50:50, at pH 1, getting 0,1899 ± 5,8.10-3 mmol expressed in ascorbic acid g-1 in extracts of V. minutiflora . While, for dosages of total flavonoids the significant variables were the type of acid and volume of acid. The best extraction obtained was: 6,748. 10-2± 2,085 10-3% expressed in quercetin. These data showed that the factorial design is an important tool in optimizing the extraction of chemical components in natural products.

Effect of the native polysaccharide of cashew-nut tree gum exudate on murine peritoneal macrophage modulatory activities.

The native polysaccharide of cashew-nut tree gum exudate (CNTG) and its arabinogalactan-protein component (CNTG-AGP) were tested by using immuno-stimulant and anti-inflammatory in vitro assays of murine peritoneal macrophage activities. In the assay for immuno-stimulant activity (without previous treatment with lipopolysaccharide; LPS), CNTG increased the production of interleukin (IL)-10 and both CNTG and CNTG-AGP decreased the concentrations of IL6. When the macrophages were incubated in the presence of LPS and CNTG a decrease in the levels of nitric oxide (NO(·)) and IFN-γ was observed. The results could explain the popular use of CNTG as an anti-inflammatory. In addition, CNTG is the main component of the cashew-nut tree gum exudate, which has been considered a versatile polymer with potential pharmaceutical and food industry applications. These data may contribute to the study of the immunomodulation activity of plant polysaccharides, as well as encourage future experiments in the field of cashew-nut tree gum exudate applications.

Efficacy of beer fermentation residue containing Saccharomyces cerevisiae cells for ameliorating aflatoxicosis in broilers.

This study aimed to determine the aflatoxin B1 (AFB1) binding capacity of a beer fermentation residue (BFR) containing Saccharomyces cerevisiae cells, and the efficacy of BFR to ameliorate the toxic effects of AFB1 on performance, serum biochemistry, and histology of broilers. The BFR was collected from a microbrewery, and the yeast cells were counted, dried, and milled before it was used in the study. In vitro evaluation of the BFR was conducted using different concentrations of AFB1 (2.0, 4.0, 8.0, 16.0, and 32.0 µg AFB1/mL) and 100 mg/10 mL of BFR at pH 3.0 or 6.0. Two hundred 1-day-old male broilers (Ross 308) were assigned to chick batteries and allowed ad libitum access to feed and water. A completely randomized design was used with 5 replicate pens of 5 chicks assigned to each of 4 dietary treatments from hatch to 21 d, which included: 1) basal diet (BD), with no BFR or AFB1; 2) BD supplemented with 1% BFR; 3) BD supplemented with 2 mg AFB1/kg of feed; and 4) BD supplemented with 2 mg AFB1/kg feed and 1% BFR. Performance variables were determined weekly, while serum analyses were performed on d 14 and 21. At the end of the study, chicks were anesthetized with carbon dioxide, euthanized by cervical dislocation, and the kidney, liver, and bursa of Fabricius were removed for determination of relative weights, and for histological evaluation. In vitro assays showed that the higher the initial AFB1 concentration in solution, the greater the AFB1 amount adsorbed by BFR at both pHs tested. Feed intake, BW gain, and concentrations of albumin, total protein, and globulin increased (P < 0.05) in broilers fed BFR+AFB1 (Diet 4), when compared to the birds receiving only AFB1 (Diet 2). Although BFR was not able to reduce or prevent the effects of AFB1 on relative weights of kidneys and liver, it reduced the severity of histological changes in the liver and kidney caused by AFB1.

Kinetics of mobile impurities and correlation functions in one-dimensional superfluids at finite temperature.

We examine the hydrodynamic approach to dynamical correlations in one-dimensional superfluids near integrability and calculate the characteristic time scale, τ, beyond which this approach is valid. For time scales shorter than τ, hydrodynamics fails, and we develop an approach based on kinetics of fermionic quasiparticles described as mobile impurities. New universal results for the dynamical structure factor relevant to experiments in ultracold atomic gases are obtained.