Folk medicine, biological activity, and chemical profiles of Brazilian Acanthaceae (Lamiales) - A review.

INTRODUCTION: The botanical family Acanthaceae (order Lamiales) potentially comprises 4900 species in 191 genera with extensive morphological, habit and habitat diversity. The family is widely distributed throughout the world but is especially rich in tropical and subtropical regions. Many of its species have great ornamental importance and are broadly used for medicinal purposes in several countries of Asia and Africa. Brazil is a main center of diversity of the family, where they are distributed across all its biomes, mainly in the herbaceous-shrub stratum. Medicinal investigations about Brazilian species are scarce, the exception being a single native species, Justicia pectoralis Jacq., that is widely used and studied chemically. AIM OF THE REVIEW: This work compiled studies that indicated folk medicinal use, investigated biological activity, or evaluated the chemical composition of Brazilian species of Acanthaceae. MATERIAL AND METHODS: Medicinal uses, investigations of biological activities and chemical data were collected and summarized through bibliographic surveys. Tables were compiled to standardize the information and the appropriate references were gathered for each species. Registration of chemical components used in the treatment of ailments and in preserving health were emphasized with the aim of stimulating future investigations. RESULTS: The breadths of habitats and morphologies of the family are directly related to its chemical diversity, as confirmed here for Brazilian species. Although the investigated species represent less than 9% of the total richness of the family in Brazil, they encompass a great diversity of chemical substances. The data indicated folk medicinal uses for 26 species and biological tests for 23, while 30 species were investigated chemically. Ruellia and Justicia were the most researched genera with 12 and 11 species, representing approximately 14% and 7% of Brazilian species of each genus, respectively. Two species are native to other countries but become naturalized in Brazil. Studies of native species were carried out in different countries around the world, with many reports of medicinal uses and biological tests. Examples of uses include anticancer and antidepressant actions, as well as activities against respiratory problems and other diseases. CONCLUSIONS: This work highlights the chemical and biological diversity of the studied Brazilian species of Acanthaceae, which emphasizes the need to expand studies with native Brazilian species.

Carbohydrate metabolism evaluation of terrestrial snail Subulina octona (Gastropoda, Subulinidae) experimentally infected by the Paratanaisia bragai digenetic trematode (Digenea, Eucotylidae).

Among the effects of the larval development of digenetic trematodes on their intermediate hosts, changes in the carbohydrate metabolism in the snails stand out. The aim of this study was to analyze, every 10 days after infection (d.p.i.), the effects of Paratanaisia bragai infection on the glycogen content in the digestive gland and cephalopedal mass in Subulina octona snail, and also verify the glucose concentration and the enzyme D- and L-lactate dehydrogenase activity (EC1.1.1.27 and EC1.1.1.28) (LDH) and the concentration of some metabolites(oxalic, succinic, pyruvic and lactic acid) presents in the hemolymph. Histochemical analisys were also performed. We verified a total increase of 54.81% in glucose concentration in infected snails and an oscillating pattern in the glycogen content in the cephalopedal mass and in the digestive gland. LDH activity shows an increase of 10 d.p.i. (+ 74.32%) and 40 d.p.i. (+ 47.81%) and decrease at 20 d.p.i. and 30 d.p.i. The concentrations of oxalic, succinic and pyruvic acids showed significant and progressive reductions; however, lactic acid had a significant increase. Histological and histochemical analysis showed a tissue disorganization in the cephalopedal mass of infected snails and morphological changes in the digestive gland. These results confirm that infection causes metabolic pathway changes in the snails due to activation of an alternative anaerobic pathway for producing energy, indicated by the increased lactic acid content and LDH activity.

Larvicidal and Fungicidal Activity of the Leaf Essential Oil of Five Myrtaceae Species.

Myrtaceae is one of the most diverse and abundant botanical families, exhibiting wide diversity in the chemical composition of essential oils (EOs). EOs have various biotechnological applications such as controlling the populations of organisms that negatively impact humans. This study aimed to extract EOs from Myrtaceae species, chemically characterize them, and evaluate their larvicidal and fungicidal effects. EOs were extracted from the leaves of Eugenia brasiliensis, Eugenia uniflora, Psidium cattleyanum, Psidium guajava, and Syzygium cumini by hydrodistillation for 3 h and characterized by chromatographic analysis. Larvaes of Aedes aegypti and colonies of Fusarium oxysporum were subjected to increasing EO concentrations to determine the larvicidal and fungicidal potential. The EOs of Eugenia and Psidium species are primarily composed of sesquiterpenes (>80 %), whereas S. cumini EO is rich in monoterpenes (more than 60 %). The Eugenia species had similar amounts of oxygenated monoterpenes, which may explain their higher larvicidal potential compared to other species, with CL50 of 86.68 and 147.46 PPM, respectively. In addition to these two study species, S. cumini showed a high inhibition of fungal growth, with more than 65 % inhibition. We demonstrated that the actions of five EOs from Myrtaceae with different biological activities are associated with chemical diversity.

Influence of microbial fermentation on the antioxidant activity of phenolic substances in Saccharomyces cerevisiae.

AIM: Using in vitro assay and eukaryotic cell model of Saccharomyces cerevisiae, we investigated the impact of microbial fermentation on the antioxidant activity of phenolic substances. METHODS AND RESULTS: Caffeic acid phenethyl ester (CAPE) and mangiferin were fermented by lactic acid bacteria (LAB), and the antioxidant activity of the fermented products was compared to that of the pure substances. This comparison was assessed using high-performance liquid chromatography (HPLC), in vitro by 2,2-Diphenyl-1-picrylhydrazyl (DPPH), and in vivo in yeast cells. The wild-type strain (BY4741) and its isogenic mutants in glutathione (Δgsh1), catalase (Δctt1), and superoxide dismutase (Δsod1) were treated with CAPE and mangiferin, fermented or not, and exposed to hydrogen peroxide (H2O2)-induced stress. The antioxidant activity was evaluated by cellular viability, intracellular oxidation, and lipid peroxidation. We expected that fermentation would change the antioxidant activity of phenolic substances. While HPLC analysis revealed changes in the composition of fermented products, significant alterations in antioxidant activity were only observed when using mutant strains. The fermentation of mangiferin increased dependency on GSH compared to the respective pure phenolic substance to resolve H2O2-induced stress. Additionally, CAPE appeared to act as a preconditioning agent, enhancing antioxidant responses, and promoting increased tolerance to H2O2 stress, and this mechanism was maintained after fermentation. CONCLUSIONS: This study highlights that fermentation impacts the enzymatic mechanism of oxidative stress resolution, even though differences could not be observed in in vitro assays or in the wild-type strain.

Peracetylation of polyphenols under rapid and mild reaction conditions.

Structural modifications are an important tool for studying the properties of naturally occurring polyphenols. Regarding the preparation of acetyl esters, the presence of hydroxyl groups stabilized by intramolecular hydrogen bonds may pose an obstacle for the peracetylation of these compounds. In this paper, we present a facile protocol for the acetylation of selected polyphenols under mild reaction conditions by using acetic anhydride, catalytic amount 4-dimethylaminopyridine (DMAP) and dimethylformamide (DMF) as solvent. Reaction conditions were adjusted for optimal formation of peracetylated polyphenols while minimizing the formation of byproducts. Butyric anhydride was employed as an alternative acylating agent and showed similar results. Reaction yields varied from 78-97%, and products were obtained in high purity, as determined by LCMS(ESI+), 1H NMR and 13C NMR.

Hydroalcoholic Extract of Encholirium spectabile Mart. (Bromeliaceae) in O/W Emulsions as an Additive against the UVB Radiation.

The use of sunscreen is one of the photoprotection measures most used by the population, so these products must offer broad-spectrum protection against UVA and UVB radiation. Encholirium spectabile, popularly known as "macambira-de-flecha," is a species characterized by its rocky outcrops and found in the Caatinga. This biome is known for extreme droughts and dry periods, and for this reason, its vegetation needed to develop resistance mechanisms. The aim of this work was to evaluate the use of E. spectabile incorporated in O/W emulsion as a potential photoprotective agent and their antioxidant activity. Four chemical constituents (ferulic acid, caffeic acid, p-coumaric acid and apigenin) were identified by HPLC-DAD analysis, and emulsions containing different concentrations (1%, 2.5% and 5%) of the extract without and with the addition of chemical filters (octyl methoxycinnamate and benzophenone-3) were prepared and submitted to the test of preliminary stability. The Q formulation demonstrated little variation in the preliminary stability test and was selected for estimated your protection against UVB and determination of in vitro protection factor UVA. The formulations remained stable during the freeze-thaw cycle; the extract despite maintaining the UVA-PF and decreasing the wavelength showed an increase in FPS from 14.4 (control) to 18.8 (control+ Es-HA80).

The impacts of pink pepper (Schinus terebinthifolius Raddi) on fatty acids and cholesterol oxides formation in canned sardines during thermal processing.

The effect of adding pink pepper (Schinus terebinthifolius Raddi) fruits during sardines canning to minimize cholesterol oxidation were investigated. Canning resulted in an exchange of fatty acids, cholesterol and cholesterol oxides between fish muscle and liquid medium (soybean oil). It also induced lipid oxidation, which was demonstrated by the degradation of fatty acids and the formation of cholesterol oxides. Cholesterol oxides increased from 39.53 ± 2.14 µg/g (raw sardines) to 116.04 ± 0.78 µg/g (control sardines) after canning. However, lower levels were found in samples with pink pepper. Additionally, chromatographic analyses showed the migration of compounds (phenolic acids, flavonoids, tannins, terpenes) from pink pepper to sardines, indicating the constituents that could have contributed to its antioxidant properties. Thus, pink pepper may be highlighted as a suitable additive to reduce the intake of cholesterol oxides, minimizing the loss of nutritional quality in canned fish.

Efficient removal of glyphosate from aqueous solutions by adsorption on Mg-Al-layered double oxides: thermodynamic, kinetic, and mechanistic investigation.

Up to 90% of glyphosate was removed in 40 min by a 2:1 Mg2Al-layered double oxide (LDO) at pH 10, and the adsorption kinetics fitted a pseudo-second-order law. The adsorption isotherms were type L, and the Langmuir model best fitted the experimental data, with qmax of 158.22 µg/mg at 25 °C. The intraparticle diffusion model suggested that the adsorption process is dependent on the thickness and formation of the film at the solution/solid interface. The XRD results excluded the intercalation of glyphosate anions, and FTIR along with solid-state 13C and 31P MAS NMR confirmed that the glyphosate anions interact through the carboxylate and/or phosphonate moieties, both in end-on and side-on modes to the LDO surface. Glyphosate removal was also investigated in the presence of different anionic species, and simultaneous adsorption showed that carbonate and phosphate ions strongly influence glyphosate removal.

Parsley (Petroselinum crispum Mill.): A source of bioactive compounds as a domestic strategy to minimize cholesterol oxidation during the thermal preparation of omelets.

This study evaluated the protective effect of parsley (Petroselinum crispum Mill.) against lipid and cholesterol oxidation in omelets prepared by air frying, pan frying, and microwaving. The bioactive composition and in vitro antioxidant capacity of parsley extract was characterized. Compounds such as phenolic acids and their derivatives (p-coumaric acid, p-coumaric acid 4-O-hexoside) and flavonoids (apigenin 7-glucoside, quercetin-O-pentosyl-hexoside) were identified in parsley by UHPLC-ESI-MS. Moreover, the presence of these bioactive constituents was investigated in omelets. Cooking induced lipid oxidation and increased the level of cholesterol oxidation products (COPs) in control omelets, which was more pronounced after air frying and microwaving. The total content of COPs increased from 40.69 ± 2.26 µg/g (raw) to 821.05 ± 13.77 µg/g (air frying), 805.21 ± 14.50 µg/g (microwaving), and 311.07 ± 13.84 µg/g (pan frying). The addition of parsley proved to be effective reducing COPs formation, mainly in air-fried samples with 0.75% parsley (81.73% of protection). Chromatographic analyses revealed the thermo-degradation of parsley compounds, since only two flavonoids detected in parsley were found in omelets containing the herb after cooking. Nonetheless, these findings indicate the potential application of parsley as a natural inhibitor of cholesterol and lipid oxidation in food systems such as omelets.

Spectroscopic-chemometric modeling of 80 humic acids confirms the structural pattern identity of humified organic matter despite different formation environments.

The structure of humic substances (HSs) and the humification process are critical topics for understanding the dynamics of carbon on the planet. This study aimed to assess the structural patterns of 80 humic acid (HA) samples isolated from different soils, namely, Histosols, Ferralsols, Cambisols, Mollisols, Planosols and vermicompost, by spectroscopic characterization using solid-state 13C nuclear magnetic resonance cross-polarization/magic angle spinning combined with chemometric techniques. All 80 HAs had a similar structural pattern, regardless of their source of origin, but they had different relative quantities of organic C species. The different structural amounts of the various organic C fractions generated different properties in each of the HAs. This explains why there were similarities in the HS functions but why the intensities of these functions varied among the samples from the different soil types and environments, confirming that HSs are a group of compounds with a structural identity distinct from the molecules that give rise to them. There appears to be no single definition for the humification process; therefore, for the soils from each source of origin, a specific humification process occurs that depends on the characteristics of the local environment. Humification can be understood as a process that is similar to a chemical reaction, where the key factor that determines the formation of the products is the structural characteristics of the reactants (organic substrates deposited in the soil). The degree to which the reaction progresses is governed by the reaction conditions (chemical, physical, and biological properties of the soil). The structural patterns for HSs obtained in this study justify the existence of HSs structured as self-assembled, hydrophilic and hydrophobic domains that, under certain conditions, can undergo transformations, altering the balance of organic carbon in the environment.

Persea americana Mill.: Evaluation of cytogenotoxicity and phytochemical prospection of leaf extracts

Abstract Persea americana Mill., belonging to the family Lauraceae, is noteworthy for the large amount of ethnopharmacological information in its regard, attributing to it many and varied medicinal properties. The tea and alcoholic extracts made from its leaves are used in folk medicine to treat various ailments. This study was designed to analyze the cytogenotoxicity and underlying chemistry of aqueous and hydroalcoholic extracts of avocado leaves, using the Allium cepa and micronucleus tests. The results obtained by applying the experimental models demonstrate that the extracts did not have a genotoxic effect at any of the concentrations analyzed, and even demonstrated a certain protective effect, possibly due to the presence of flavonoids and phenols, both of which are antioxidant substances. However, the extracts did present a cytotoxic effect. There were numerous karyorrhectic cells and those with nuclear alterations related to cell death. At the highest concentrations, it was possible to observe cytoplasmic alterations and binucleated cells. The extracts also caused a significant reduction in the number of cells undergoing division. These effects can be a response to the phytochemical agents present in the extracts. The results suggest that the extracts contain bioactive components that deserve further studies related to cancer therapies.

Hexane fraction from Brazilian Morus nigra leaves improved oral carbohydrate tolerance and inhibits α-amylase and α-glucosidase activities in diabetic mice.

Morus nigra, popularly known as mulberry, has been traditionally used as anti-diabetic herbal medication. This study focused on hexane fraction from Brazilian M. nigra leaves (Hex-Mn) effects on digestion and absorption of carbohydrate in diabetic mice. The high-performance liquid chromatography (HPLC) analysis was performed, and showed the presence of flavonoids isoquercetin and kaempferol-3-O-rhamnoside. Hex-Mn did not alter oral glucose tolerance test; however, it prevented hyperglycemia in oral sucrose and starch tolerance test in diabetic mice. Also, Hex-Mn was more efficient to inhibit the α-glucosidase, showing lower inhibitory effect on α-amylase activity in vitro. The results suggest that Hex-Mn may delay the carbohydrate digestion, but not glucose transport through brush border membrane of the intestine, which contribute with reduction in postprandial hyperglycemia in mice. Hex-Mn has antihyperglycemic effect by attenuating the carbohydrate digestion in diabetic mice, which could be explained, at least in part, by the presence of isoquercetin and kaempferol-3-O-rhamnoside.

Metabolic characterization and oil profile of sunflower cultivars cultivated with increasing nitrogen doses / Caracterização metabólica e perfil do óleo de cultivares de girassol cultivados sob doses crescentes de nitrogênio

Sunflower (Helianthus annuus L.) has great economic importance due to its oil yield and quality. Among the factors influencing these parameters, nitrogen fertilization stands out. In this study we evaluated the effect of different N-urea doses (0,10,30,50,90,130 kg N-urea ha-1) at planting and 30 days after emergency on soluble fractions, oil profile and yield of three sunflower cultivars (BRS324, Catissol 01and Neon). Plants were harvested at the flowering stage for metabolic study, and at the end of the cycle for oil extraction and characterization. The Catissol 01 genotype presented the highest N-NO3- accumulation capacity, mainly in the stem. The Neon genotype presented the highest achene production at 30 and 50 kg N ha-1. Oleic oil had the highest yield, with the Catissol 01 and Neon cultivar standing out. Among the cultivars, Catissol 01 is economically more suitable for biofuel production, when cultivated at 50 kg N ha-1 since higher N doses did not result in increased oil yield.

O girassol é uma espécie com importante valor econômico pela qualidade e rendimento de óleo. Entre os fatores que influenciam esses parâmetros se destaca a fertilização nitrogenada. Este trabalho avaliou o efeito de doses crescentes de N-uréia (0, 10, 30, 50, 90, 130 kg de N-Uréia ha-1 aplicadas no plantio e aos 30 dias após a emergência) sobre as frações solúveis, rendimento e perfil do óleo de três genótipos de girassol (BRS324, Neon e Catissol 01). As plantas foram coletadas no estádio de floração para o estudo metabólico e ao final do ciclo para a extração e caracterização de óleo. O genótipo Catissol 01 apresentou maior capacidade de acúmulo de N-NO3-, preferencialmente no caule. A maior produção de óleo por planta foi observada no BRS324, nas doses entre 30 e 50 kg N ha-1, embora o genótipo Neon tenha apresentado a maior produção de aquênios. O ácido oléico foi o de maior rendimento com destaque para os genótipos Catissol 01 e Neon. Dentre os genótipos avaliados, o Catissol 01 é economicamente mais indicado para a produção de óleo destinada ao biocombustível, quando cultivado com a dose de 50 kg N ha-1, pois doses superiores de N não resultam em aumento na produção de óleo.

Grain production fatty acid and oil profile from sunflower cultivars receiving different boron doses / Produção de grãos, perfil de óleo e ácido graxo em cultivares de girassol submetidos a diferentes doses de boro

Among the main factors that affect the productivity of crops is deficiency of nutrients. Boron (B) is an essential micronutrient for plants, and sunflower is one of the most sensitive plants to deficiency of the element. Its inadequate supply can impair sunflower plants' metabolism and grain and oil yield. The objective of this study was to assess the effect of different boron doses on the production of sunflower grains and the content and quality of the oil obtained from them. The experimental design was randomized blocks in a factorial scheme with three cultivars (Helio251, BRS323, BRS324) and four B doses (0, 2.5, 5.0, 8.0 kg ha-1). Two harvests were performed, the first in the R5 reproductive stage and the second at the end of the R9 cycle. In both cases, the levels of B in the capitulum were measured. At the end of the cycle, the grain yield, crude protein and oil content in the grains and fatty acid profile were analyzed. The cultivars responded differently to the treatments with B. The boron fertilization influenced the grain yield and oil content, but was not correlated with the profile of the majority unsaturated fatty acids and crude protein in the grains. Variations were observed in the fatty acid profile between the cultivars, an important aspect that needs to be evaluated according to the purpose of the production. In soil with lower availability of B, cultivar BRS323 was most efficient in B uptake, grain yield and oil content and quality.

Dentre os principais fatores que afetam a produtividade das culturas está a deficiência de nutrientes. O Boro (B) é um micronutriente essencial para plantas, e o girassol é uma das mais sensíveis à deficiência desse elemento. Seu fornecimento inadequado pode prejudicar o metabolismo, a produção de óleo e grãos das plantas de girassol. O objetivo deste estudo foi avaliar o efeito de diferentes doses de boro na produção de grãos, conteúdo a qualidade do óleo de girassol. O experimento foi conduzido em delineamento de blocos ao acaso em esquema fatorial com três cultivares (Helio251, BRS323, BRS324) e quatro doses de B (0; 2,5; 5,0; 8,0 kg ha-1). Foram realizadas duas coletas, a primeira na fase reprodutiva R5 e a segunda no final do ciclo R9. Em ambos os casos, os níveis de B no capítulo foram medidos. No final do ciclo, foram analisados a produção de grãos, teor de proteína bruta e óleo nos grãos e perfil de ácidos graxos. Os cultivares responderam diferentemente aos tratamentos com B. A adubação com boro influenciou o rendimento de grãos e teor de óleo, mas não se correlacionou com o perfil da maioria dos ácidos graxos insaturados e da proteína bruta nos grãos. Foram observadas variações no perfil de ácidos graxos entre cultivares, um aspecto importante que precisa ser avaliado de acordo com a finalidade da produção. No solo com menor disponibilidade de B, o cultivar BRS323 foi mais eficiente na absorção de B, rendimento de grãos, teor e qualidade de óleo.

Effect of aroeira (Schinus terebinthifolius Raddi) fruit against polyunsaturated fatty acids and cholesterol thermo-oxidation in model systems containing sardine oil (Sardinella brasiliensis).

This study evaluated the protective effect of ground aroeira (Schinus terebinthifolius Raddi) fruit addition against fatty acids and cholesterol oxidation in model systems containing sardine oil (Sardinella brasiliensis) during heating (150 and 180 °C). High temperatures reduced the amount of essential polyunsaturated fatty acids and caused the formation of oxidized products. Total cholesterol oxides content increased from 58.9 ± 0.26 to 577.5 ± 2.14 µg/g oil, after heating at 180 °C. However, aroeira significantly protected lipids from oxidation. Although the synthetic antioxidant applied as standard (butylated hydroxytoluene) showed greater results, it was used in the maximum concentration permitted by Brazilian legislation (0.01%), suggesting that aroeira fruit could be used as a natural antioxidant for the food industry. The protective effect of aroeira may be correlated to its antioxidant capacity and the presence of bioactive compounds which were identified by UHPLC-ESI-MS in the aroeira extract.

Vanilla bahiana, a contribution from the Atlantic Forest biodiversity for the production of vanilla: A proteomic approach through high-definition nanoLC/MS.

Only a few cultivated species of Vanilla are used to produce vanilla, despite the high demand, predatory exploitation, and low genetic variability that threaten the production of natural vanilla. Vanilla bahiana pods from the Atlantic Forest may be an alternative source of natural vanilla. This study applied bottom-up and shotgun proteomics analysis to identify proteins related to flowering, fruiting, and vanilla-flavor production. Extraction solutions, including Tris-HCl buffer, ß-mercaptoethanol and SDS, were assayed. SDS proved to be feasible for extraction of Vanilla fruit proteins and could be an alternative to the phenol method of protein extraction. Progenesis QI for Proteomics (QIP) software loaded with an Orchidaceae database identified 2326 proteins in our samples. Among these, 75 were highlighted as useful for the synthesis of compounds related to vanilla flavor, such as vanillin synthase, which was successfully extracted with 1% SDS, which also improved the variety of the extracted proteins. The proteins identified in V. bahiana pods indicate the enzymatic potential of this species, as further validated by quantifying the vanilla in the samples.

Discovery of novel dual-active 3-(4-(dimethylamino)phenyl)-7-aminoalcoxy-coumarin as potent and selective acetylcholinesterase inhibitor and antioxidant.

A series of 3-substituted-7-aminoalcoxy-coumarin was designed and evaluated as cholinesterase inhibitors and antioxidants. All compounds were effective in inhibiting AChE with potencies in the nanomolar range. The 3-(4-(dimethylamino)phenyl)-7-aminoethoxy-coumarin (6a) was considered a hit, showing good AChE inhibition potency (IC50 = 20 nM) and selectivity (IC50 BuChE/AChE = 354), quite similar to the reference drug donepezil (IC50 = 6 nM; IC50 BuChE/AChE = 365), also presenting antioxidant properties, low citotoxicity and good-predicted ADMET properties. The mode of action (mixed-type) and SAR analysis for this series of compounds were described by means of kinetic and molecular modeling evaluations.

New compounds of Siolmatra brasiliensis and inhibition of in vitro protein glycation damage.

Twenty compounds were isolated from the hydroethanolic extract of the stems of Siolmatra brasiliensis, five flavonoids, two lignans, one glucosyl phytosterol, seven nor-cucurbitacins, one new phenolic derivative named siolmatrin (1) and four new dammarane-type saponins named siolmatrosides II-V (2-5), the structures of the compounds were assigned by means of 1D and 2D NMR experiments and HRESIMS of the natural compounds and some acetyl derivatives. The effects of the crude hydroethanolic extract (SbExt) and the ethyl acetate fraction (SbEtAc) of Siolmatra brasiliensis stems on the formation of advanced glycation end-products (AGEs) were also investigated. In the in vitro model system of protein glycation using bovine serum albumin (BSA) and glucose, addition of SbExt or SbEtAc inhibited the formation of fluorescent AGEs, in parallel to minor levels of fructosamine (SbEtAc) and markers of tyrosine and tryptophan oxidation (SbExt and SbEtAc). Protein crosslinking, which represents changes of late stages of protein glycation, was reduced in the presence of SbExt and SbEtAc. Siolmatra brasiliensis stems seem to be a promising source of compounds having ability to prevent glycoxidation changes, arising as an interesting option to be studied as a complementary therapy for complications of diabetes.

Synthesis and molecular modelling studies of pyrimidinones and pyrrolo[3,4-d]-pyrimidinodiones as new antiplasmodial compounds.

BACKGROUND Malaria is responsible for 429,000 deaths per year worldwide, and more than 200 million cases were reported in 2015. Increasing parasite resistance has imposed restrictions to the currently available antimalarial drugs. Thus, the search for new, effective and safe antimalarial drugs is crucial. Heterocyclic compounds, such as dihydropyrimidinones (DHPM), synthesised via the Biginelli multicomponent reaction, as well as bicyclic compounds synthesised from DHPMs, have emerged as potential antimalarial candidates in the last few years. METHODS Thirty compounds were synthesised employing the Biginelli multicomponent reaction and subsequent one-pot substitution/cyclisation protocol; the compounds were then evaluated in vitro against chloroquine-resistant Plasmodium falciparum parasites (W2 strain). Drug cytotoxicity in baseline kidney African Green Monkey cells (BGM) was also evaluated. The most active in vitro compounds were evaluated against P. berghei parasites in mice. Additionally, we performed an in silico target fishing approach with the most active compounds, aiming to shed some light into the mechanism at a molecular level. RESULTS The synthetic route chosen was effective, leading to products with high purity and yields ranging from 10-84%. Three out of the 30 compounds tested were identified as active against the parasite and presented low toxicity. The in silico study suggested that among all the molecular targets identified by our target fishing approach, Protein Kinase 3 (PK5) and Glycogen Synthase Kinase 3ß (GSK-3ß) are the most likely molecular targets for the synthesised compounds. CONCLUSIONS We were able to easily obtain a collection of heterocyclic compounds with in vitro anti-P. falciparum activity that can be used as scaffolds for the design and development of new antiplasmodial drugs.

Bulimulus tenuissimus (mollusca) as a new potential host of Angiostrogylus cantonensis (nematoda), a histological and metabolic study.

The terrestrial gastropod Bulimulus tenuissimus is widespread in South America. It is an intermediate host of many parasites, but there are no records of infection of this snail by Angiostrongylus cantonensis, despite the occurrence of this parasite and angiostrongyliasis cases in the same areas in which B. tenuissimus occurs. For this reason, it is important investigate the susceptibility of B. tenuissimus to A. cantonensis-infection, since it can be used as intermediate host of A. cantonensis, increasing the list of terrestrial gastropods that infect wild and domestic animals and humans with this parasite. The purpose of this study was to evaluate the susceptibility of B. tenuissimus to experimental infection with L1 larvae of A. cantonensis. The snails were exposed to 1200 L1 larvae and it was possible observe many developing larvae in the cephalopedal mass and mantle tissues, with intense hemocyte infiltration and collagen deposition, but no typical granuloma structures were formed. The glucose content and lactate dehydrogenase activity in the hemolymph varied, indicating an increase of anaerobic energy metabolism in the middle of infection, but with a tendency to return to normal values at the end of pre-patent period. This was corroborated by the marked reduction in the glycogen content in the cephalopedal mass and digestive gland in the first and second week after exposure, followed by a slight increase in the third week. The content of pyruvic acid in the hemolymph was 14.84% lower at the end of pre-patent period, and oxalic acid content was 41.14% higher. These results indicate an aerobic to anaerobic transition process. The PAS reaction showed a large amount of glycogen inside the developing larvae and muscular tissues of the cephalopedal mass, indicating that despite the high consumption of this polysaccharide by the parasite, the snail is able to maintain its energy metabolism based on carbohydrates. The results reveal that B. tenuissimus is a robust host, which can live with the developing larvae of A. cantonensis and overcome the metabolic damages resulting from parasitism.