Anti-inflammatory effects of naringenin 8-sulphonate from Parinari excelsa Sabine stem bark and its semi-synthetic derivatives.

The inflammatory response is a vital mechanism for repairing damage induced by aberrant health states or external insults; however, persistent activation can be linked to numerous chronic diseases. The nuclear factor kappa ß (NF-κB) inflammatory pathway and its associated mediators have emerged as critical targets for therapeutic interventions aimed at modulating inflammation, necessitating ongoing drug development. Previous studies have reported the inhibitory effect of a hydroethanol extract derived from Parinari excelsa Sabine (Chrysobalanaceae) on tumour necrosis factor-alpha (TNF-α), but the phytoconstituents and mechanisms of action remained elusive. The primary objective of this study was to elucidate the phytochemical composition of P. excelsa stem bark and its role in the mechanisms underpinning its biological activity. Two compounds were detected via HPLC-DAD-ESI(Ion Trap)-MS2 analysis. The predominant compound was isolated and identified as naringenin-8-sulphonate (1), while the identity of the second compound (compound 2) could not be determined. Both compound 1 and the extract were assessed for anti-inflammatory properties using a cell-based inflammation model, in which THP-1-derived macrophages were stimulated with LPS to examine the treatments' effects on various stages of the NF-κB pathway. Compound 1, whose biological activity is reported here for the first time, demonstrated inhibition of NF-κB activity, reduction in interleukin 6 (IL-6), TNF-α, and interleukin 1 beta (IL-1ß) production, as well as a decrease in p65 nuclear translocation in THP-1 cells, thus highlighting the potential role of sulphur substituents in the activity of naringenin (3). To explore the influence of sulphation on the anti-inflammatory properties of naringenin derivatives, we synthesized naringenin-4'-O-sulphate (4) and naringenin-7-O-sulphate (5) and evaluated their anti-inflammatory effects. Naringenin derivatives 4 and 5 did not display potent anti-inflammatory activities; however, compound 4 reduced IL-1ß production, and compound 5 diminished p65 translocation, with both exhibiting the capacity to inhibit TNF-α and IL-6 production. Collectively, the findings demonstrated that the P. excelsa extract was more efficacious than all tested compounds, while providing insights into the role of sulphation in the anti-inflammatory activity of naringenin derivatives.

Diversity, distribution and conservation of land mammals in Mauritania, North-West Africa.

Detailed knowledge about biodiversity distribution is critical for monitoring the biological effects of global change processes. Biodiversity knowledge gaps hamper the monitoring of conservation trends and they are especially evident in the desert biome. Mauritania constitutes a remarkable example on how remoteness and regional insecurity affect current knowledge gaps. Mammals remain one of the least studied groups in this country, without a concerted species checklist, the mapping of regions concentrating mammal diversity, or a national assessment of their conservation status. This work assessed the diversity, distribution, and conservation of land mammals in Mauritania. A total of 6,718 published and original observations were assembled in a spatial database and used to update the occurrence status, distribution area, and conservation status. The updated taxonomic list comprises 107 species, including 93 extant, 12 Regionally Extinct, and 2 Extinct in the Wild. Mapping of species distributions allowed locating concentrations of extant mammal species richness in coastal areas, along the Senegal River valley, and in mountain plateaus. Recent regional extinction of large-sized Artiodactyla and Carnivora has been very high (11% extinct species). From the extant mammals, 11% are threatened, including flagship species (e.g., Addax nasomaculatus and Panthera pardus). Species richness is poorly represented by the current protected areas. Despite the strong advances made, 23% of species categorise as Data Deficient. Persisting systematics and distribution uncertainties require further research. Field surveys in currently unexplored areas (northern and south-eastern regions) are urgently needed to increase knowledge about threatened mammals. The long-term conservation of land mammals in Mauritania is embedded in a complex web of socioeconomic and environmental factors that call for collaborative action and investment in sustainable human development. The current work sets the baseline for the future development of detailed research studies and to address the general challenges faced by mammals and biodiversity in the country.

Horticultural performance of 'Fuji Suprema' and 'Maxi Gala' apple trees trained at Tall Spindle and Bi-Axis systems grafted on different rootstocks in Southern Brazil / Comportamento agronômico de macieiras 'Fuji Suprema' e 'Maxi Gala' conduzidas em Tall Spindle e Bi-Axis enxertadas em diferentes porta-enxertos no Sul do Brasil

The use of new rootstocks combined with different training systems have been studied to increase productivity, fruit quality, and reduce costs. Another important factor is the validation of studies under replanting conditions, due to the growing limitation of new areas for planting commercial apple orchards in Brazil. The present study aimed to evaluate the behavior of 'Fuji Suprema' and 'Maxi Gala' apple trees in two training systems grafted on two rootstocks. The study occurred during the seasons 2016/17, 2017/18 and 2018/19, in an orchard located in southern Brazil in an area previously cultivated with apple trees. A randomized block design consisting of a 2x2 factorial was used, with Tall Spindle and Bi-Axis as the training system and 'M.9' and 'G.213' as rootstocks of Fuji Suprema and Maxi Gala cultivars. Variables were evaluated to determine tree vigor, as well as yield and fruit quality characteristics. It was observed that 'G.213' promoted higher vigor for both cultivars as well as the Bi-Axis training system in the Maxi Gala cultivar. The highest yield was observed in Tall Spindle as well as the rootstock 'G.213' in both cultivars. The most significant changes on fruit quality occurred in the Bi-Axis training system, presenting higher intensity of red color as well as 'Maxi Gala' grafted on 'G.213' rootstock.

A utilização de novos porta-enxertos e diferentes sistemas de condução tem sido estudado para aumentar a produtividade, qualidade dos frutos e reduzir custos. Outro fator importante é a validação de estudos em condições de replantio, devido à crescente limitação de novas áreas para o plantio comercial de pomares de macieiras no Brasil. O presente estudo teve como objetivo avaliar o comportamento de macieiras 'Fuji Suprema' e 'Maxi Gala' em dois sistemas de condução enxertados sobre dois porta-enxertos. O estudo ocorreu durante as safras 2016/17, 2017/18 e 2018/19, em um pomar localizado no sul do Brasil, em área previamente cultivada com macieiras. Utilizou-se delineamento de blocos casualizados, consistindo em um fatorial 2x2, sendo Tall Spindle e Bi-Axis como sistemas de condução e 'M.9' e 'G.213' como porta-enxertos das cultivares Fuji Suprema e Maxi Gala. Foram avaliadas variáveis para determinar o comportamento vegetativo, bem como as características de produtividade e qualidade dos frutos. Observou-se que 'G.213' promoveu maior vigor para ambas cultivares, assim como o sistema de condução Bi-Axis na cultivar Maxi Gala. O maior rendimento foi observado nas macieiras conduzidas em Tall Spindle e enxertadas sobre 'G.213' em ambas cultivares. As mudanças mais significativas na qualidade dos frutos ocorreram nas macieiras conduzidas em Bi-Axis, apresentando maior intensidade de coloração vermelha, assim como na macieira 'Maxi Gala' enxertada sobre 'G.213'.

Geneva® Series Rootstocks for Apple Trees Under Extreme Replanting Conditions in Southern Brazil.

Geneva® rootstocks in Brazil are known to be efficient in controlling vigor, and are precocious and resistant to diseases. The objective of this study was to evaluate the performance of apple tree cultivars grafted on the Geneva® rootstocks in severe replant disease areas, by planting 60 days after the eradication. The experiments were implemented in 2017, in São Joaquim and Vacaria. The Gala Select and Fuji Suprema cultivars were grafted onto 'G.202', 'G.814', 'G.210', and 'G.213' rootstocks in the Tall Spindle training system. In 2018/2019, total thinning was carried out to promote plant growth. In São Joaquim, partial thinning was carried out in 2019/2020 harvest of 'Gala Select'. The rootstocks were divided into two groups based on vigor, for both areas and cultivars. 'G.202' and 'G.213' were 40% less vigorous than 'G.210' and 'G.814'. For 'Gala Select', the extreme non-fallow condition mainly affected the vigor and productivity of 'G.213' in both areas. At the end of two harvests, 'G.213' was 17% less productive than 'G.210', contrary to what is observed in areas where the fallow period is respected. However, 'G.213' confirmed a greater yield efficiency, which was 27% higher than 'G.210'. This suggests that a perspective of forecasting production for the third crop is higher for 'G.213' than for 'G.210'. In the case of 'Fuji Suprema', the G.210 rootstock was the most productive in both areas. In São Joaquim, 'G.202' matched 'G.210' in productivity and efficiency as it sprouts better in colder regions. Considering the fruit quality, 'G.213' anticipated the maturation with fruits of larger size and higher total soluble solids (TSS) in both areas and cultivars, making it possible to anticipate the harvest. It was concluded that the non-fallow condition does not alter the relative differences in vigor and fruit quality among the rootstocks. However, notwithstanding the overall replant tolerance of these rootstocks, it does reduce productivity by mainly affecting less vigorous rootstocks that need about three crops to overcome the allelopathic effects of the soil and start growing normally. The G.210 semi-dwarfing rootstock is an alternative for the immediate conversion of apple orchards of Gala Select and Fuji Suprema cultivars in southern Brazil.

Activation of caspase-3 in gastric adenocarcinoma AGS cells by Xylopia aethiopica (Dunal) A. Rich. fruit and characterization of its phenolic fingerprint by HPLC-DAD-ESI(Ion Trap)-MSn and UPLC-ESI-QTOF-MS2.

While the fruits of Xylopia aethiopica (Dunal) A. Rich. are important in African countries as a local trade product, their composition remains scarcely investigated. Phenolic fingerprint is herein delivered through HPLC-DAD-ESI(Ion Trap)-MSn and UPLC-ESI-QTOF-MS2 analysis, six cinnamoylquinic acid derivatives and twenty-four flavonoid glycosides being determined, chrysoeriol-7-O-glycosides being the main constituents. A cytotoxicity screening of twenty-eight hydroethanol extracts, obtained from a collection of Guinea-Bissauan plants, against A549 and AGS carcinoma cells, revealed the selective and potent effect towards AGS cells (IC50 = 151 × 10-3 g L-1), upon exposure to the extract from X. aethiopica fruits. Additional experiments demonstrated insignificant effect on LDH release at 151 × 10-3 g L-1, morphological analysis further suggesting induction of apoptosis. Pro-apoptotic effects were confirmed, as the extract enabled the activation of the effector caspase-3, broadening the knowledge on the anticancer mechanisms elicited by the fruits of X. aethiopica. Phenolic constituents might contribute to the cytotoxic effects, particularly via caspase-3 activation. Considering that X. aethiopica fruit is very often referred as an anticancer ingredient in Africa, but mainly the potent cytotoxicity herein recorded, our results call for additional research aiming to identify non-phenolic constituents contributing to the effects and also to further detail the anticancer mechanisms.

Cassia sieberiana DC. leaves modulate LPS-induced inflammatory response in THP-1 cells and inhibit eicosanoid-metabolizing enzymes.

ETHNOPHARMACOLOGICAL RELEVANCE: According to ethnobotanical surveys, Cassia sieberiana DC. (1825) is a particularly reputed species in African folk Medicine, namely due to the application of its leaves and roots for the treatment of diseases and symptomatology that appear to be related with an inflammatory background. In contrast with the roots of the plant, the leaves remain to be investigated, which prompted us to further detail mechanisms underlying their anti-inflammatory properties, by using in vitro models of disease. AIM OF THE STUDY: Considering its use in the amelioration and treatment of conditions that frequently underlie an inflammatory response, C. sieberiana leaves extract was prioritized amongst a collection of extracts obtained from plants collected in Guinea-Bissau. As such, this work aims to deliver experimental data on the anti-inflammatory properties of C. sieberiana leaf and to establish possible associations with its chemical composition, thus providing a rationale on its use in folk Medicine. MATERIALS AND METHODS: The chemical profile of an hydroethanol extract obtained from the leaves of the plant was established by HPLC-DAD-ESI/MSn in order to identify bioactives. The extract and its main compound were tested towards a series of inflammatory mediators, both in enzymatic and cell-based models. The capacity to interfere with the eicosanoid-metabolizing enzymes 5-lipoxygenase (5-LOX), cyclooxygenase-1 (COX-1) and -2 (COX-2) was evaluated in cell-free systems, while the effects in interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α) levels produced by THP-1 derived macrophages were assessed through ELISA. RESULTS: HPLC-DAD-ESI/MSn analysis of the extract elucidated a chemical profile qualitatively characterized by a series of anthraquinones, particularly rhein derivatives, and nine flavonols, most of which 3-O-glycosylated. Considering the concentrations of the identified compounds, quercetin was detached as the main component. Effects of the hydroethanol extract obtained from C. sieberiana leaves against key enzymes of the arachidonic acid cascade were recorded, namely a concentration-dependent inhibition against 5-LOX, at concentrations ranging from 16 to 250 µg mL-1 and a selective inhibitory action upon COX-2 (IC50 = 3.58 µg mL-1) in comparison with the isoform COX-1 (IC50 = 9.10 µg mL-1). Impact on inflammatory cytokines was also noted, C. sieberiana leaf extract significantly decreasing IL-6 levels in THP-1 derived macrophages at 250 and 500 µg mL-1. In contrast, TNF-α levels were found to be increased in the same model. Quercetin appears to partially account for the observed effects, namely due to the significant inhibitory effects on the activity of the arachidonic acid metabolizing enzymes COX-2 and 5-LOX. CONCLUSIONS: The anti-inflammatory effects herein reported provide a rationale for the use of C. sieberiana leaves in African folk practices, such as in the treatment of arthritis, rheumatism and body aches. Considering the occurrence of flavonoidic and anthraquinonic constituents, as well as the observed anti-inflammatory properties of quercetin, recorded effects must be related with the presence of several bioactives.

Anti-inflammatory properties of Xylopia aethiopica leaves: Interference with pro-inflammatory cytokines in THP-1-derived macrophages and flavonoid profiling.

ETHNOPHARMACOLOGICAL RELEVANCE: Ethnopharmacological surveys on Guinea-Bissauan flora reveal that several species are used to treat or ameliorate the symptomatology of conditions with an inflammatory background. As such, extracts obtained from a series of plants recorded in those surveys were screened for their anti-inflammatory properties, a hydroethanolic extract obtained from the leaves of Xylopia aethiopica (Dunal) A. Rich, (Annonaceae), used on the treatment of headache, muscular pain and rheumatic pain, scoring positively and being further investigated. AIM OF THE STUDY: In order to identify species with anti-inflammatory properties, extracts were screened for their ability to interfere with LPS-induced TNF-α levels. Since significant effects were recorded upon treatment with the extract of the leaves obtained from X. aethiopica, further assays were conducted to elucidate additional mechanisms underlying its anti-inflammatory potential. Since little is known on the chemical composition of the plant, we also aimed to characterise its phenolic profile. MATERIALS AND METHODS: Interference with cytokines was evaluated by ELISA assay, through the quantification of TNF-α and IL-6 levels in the culture medium collected from LPS-activated THP-1-derived-macrophages. Inhibition of 5-lipoxygenase was assessed based on the oxidation of linoleic acid to 13-hydroperoxylinoleic acid. Characterization of the phenolic profile was attained by HPLC-DAD. RESULTS: Evaluation of TNF-α levels in LPS-challenged THP-1 macrophages evidenced a significant inhibition (>90%) upon treatment with the hydroethanolic extract obtained from X. aethiopica leaves at a concentration of 500 µg/mL. Additional anti-inflammatory effects were recorded, including a significant decrease on IL-6 levels at 250 and 500 µg/mL. The extract proved to be active towards 5-LOX, leading to significant inhibition at concentrations ranging from 16 to 250 µg/mL (IC50 = 85 µg/mL). Phenolic profiling allowed the identification and quantitation of eight constituents, including caffeoylquinic acids (1-3), mono-O-glycosylated flavonols (5-8), and the mono-O-glycosyl flavone luteolin-7-O-glucoside (4). The main phenolic constituent, kaempferol-3-O-rutinoside (8), was found to significantly contribute to the anti-inflammatory effects, namely through the inhibition of 5-LOX. However, no effects on the decrease of TNF-α and IL-6 levels caused by this phenolic compound were found. CONCLUSION: The anti-inflammatory effects of X. aethiopica leaves are demonstrated experimentally, thus substantiating its use in folk Medicine. Relevantly, the observed anti-inflammatory properties can stimulate further studies in order to fully unveil the therapeutic potential of the plant, namely as a source of phenolic compounds with a significant ability to interfere with conventional inflammatory targets.

Accessing lipophilicity of drugs with biomimetic models: A comparative study using liposomes and micelles.

Lipophilicity is a physicochemical property of crucial importance in drug discovery and drug design. Biomimetic models, such as liposomes and micelles, constitute a valuable tool for the assessment of lipophilicity through the determination of partition coefficients (log Kp). However, the lack of standardization hampers the judgment about which model or method has the best and broadest passive drug permeation predictive capacity. This work provides a comparative analysis between the methodologies based on biomimetic models to determine the partition coefficient (log Kp). For that purpose, a set of reference substances preconized by the Organization for Economic Cooperation and Development (OECD) guidelines was used. The biomimetic models employed were liposomes and micelles composed by 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) and hexadecylphosphocholine (HePC), respectively. Both lipids were used as representative phospholipids of natural membranes. The partition coefficients between biomimetic models and aqueous phases were determined by derivative spectroscopy at physiological conditions (37 °C and pH 7.4). The partition coefficients obtained using biomimetic models are quite different and more reliable than the ones obtained using an octanol/water system. Comparing the performance of the two biomimetic models, micelles revealed to be suitable only for substances with high molar absorption coefficient and log Kp > 3, but in general liposomes are the best model for accessing lipophilicity of drugs. Furthermore, a comparison between experimental data and the partition coefficients determined by the computational method COSMOmic is also provided and discussed. As a final summarizing result, a decision tree is provided in order to guide the selection of a tool for assessing the lipophilicity of drugs.

Raleio de cachos sobre o potencial enológico da uva 'Cabernet Franc' em duas safras / A survey of clusters thinning in the 'Cabernet Franc' winemaking potential in two seasons

RESUMO:O presente trabalho teve como objetivo avaliar a maturação tecnológica e fenólica das uvas na variedade 'Cabernet Franc', submetida a diferentes níveis de raleio de cachos, de modo a estabelecer critérios que contribuam para definir o manejo mais apropriado para a obtenção de uvas destinadas à elaboração de vinhos finos, em regiões acima de 900m de altitude. Os ensaios foram conduzidos durante as safras 2009/10 e 2010/11 em um vinhedo comercial a 1,230m de altitude, localizado no município de São Joaquim, SC, coordenadas 28º 17' 39" S e 49º 55' 56" W. Foi utilizada a variedade 'Cabernet Franc', enxertada sobre 'Paulsen 1103', conduzida em espaldeira, com espaçamento de 3,0m x 1,2m e cobertura anti-granizo. Os níveis de raleio de cachos, ajustados na virada de cor "véraison", corresponderam à produção máxima, com reduções percentuais em sua produtividade em 25%, 50% e 75%. Observou-se que, em região de altitude, a prática de raleio de cachos modifica as características químicas da uva 'Cabernet Franc', aumentando o pH, reduzindo o teor de SS do mosto e polifenóis da casca. A realização do raleio de cachos, além de reduzir a produção por área, não teve um efeito compensatório na qualidade do mosto, além de não ter sido observado equilíbrio vegetativo/produtivo das plantas. A redução da carga através da prática do raleio de cachos não gerou os benefícios esperados para a cv 'Cabernet Franc', cultivada em região de altitude nas duas safras avaliadas.

ABSTRACT:This study aims to evaluate the ripening of 'Cabernet Franc's' grape berries submitted to different levels of clusters thinning in order to establish criteria that will help to define the most appropriate management for winemaking in regions above 900m. The experiment was conducted during the growing seasons of 2009/10 and 2010/11 in a commercial vineyard (28º 17' 39" S e 49º 55' 56" W, 1,230m), located in São Joaquim, SC. Plants are grafted on Paulsen 1103 and conducted in vertical shooting positioning trellis, spacing 3.0 x 1.2m and covered with hail protection net. Levels of clusters thinning, set at "veraison", corresponded to maximum production, and percentage reductions in productivity by 25%, 50% and 75%. In the region of altitude, the practice of clusters thinning modifies the chemical composition of 'Cabernet Franc's' grape berries. Besides reducing the production per area, this practice does not have a compensatory effect of lower productivity in the quality of wine and equilibrium vegetative/productive plants as well. Reducing production through clusters thinning did not reach the expected benefits for cv 'Cabernet Franc' in this survey.

General aspects of physalis cultivation / Aspectos gerais da cultura da physalis

The Physalis peruviana L. is an exotic fruit that belongs to the Solanaceae family with recent production in Brazil. This is presented as an alternative production with nutritional potential and economic value. The cape gooseberry plant has a high added value that can be used from its root to the fruit itself. The roots and leaves are rich in medicinal properties that are used in pharmacology. The fruit is sweet and have good content of vitamins A, C, iron, phosphorus and fiber, often used in making jellies, jams, juices and ice creams. To improve the plant canopy, but also contribute to the quality and appearance of the fruit produced some cultural practices such as staking, training systems, pruning and thinning are used. The aim of this review is to provide technical and scientific data about the culture of physalis.

A Physalis peruviana L. é uma fruta exótica pertencente à família Solanaceae com produção recente no Brasil. Esta se apresenta como uma alternativa de produção com potencial valor nutricional e econômico. A planta da fisalis possui um alto valor agregado, podendo ser utilizada desde sua raiz até o fruto propriamente dito. As raízes e as folhas são ricas em propriedades medicinais que são utilizadas na farmacologia. O fruto é açucarado e com bom conteúdo de vitaminas A, C, ferro, fósforo e fibras, muito utilizado na fabricação de geleias, doces, sucos e sorvetes. Para melhorar o dossel vegetativo da planta, como também contribuir para a qualidade e aparência do fruto produzido, utiliza-se, durante seu cultivo, algumas práticas culturais, como tutoramento, condução, poda e desbrote. O objetivo desta revisão é fornecer dados técnico-científicos sobre a Cultura da Physalis.