Introduction: Several plant species found in the Amazon have therapeutic properties.
Therefore, several biocompounds such as isoflavones, tocotrienols, geranylgeraniol
and anthocyanins are present in plant species such as Bixa orellana and Euterpe
oleracea, providing various therapeutic effects. These plants are known for their health
benefits, such as reducing lipids, especially for menopausal women. In this context,
targets for pharmacological technologies are considered to obtain active ingredients
for the treatment of chronic diseases, such as atherogenic dyslipidemia, which is a
metabolic condition associated with an increased risk of cardiovascular diseases.
Objective: To evaluate the effect of the nutraceuticals Ormona® RC and Ormona® SI
on dyslipidemia and its complications induced by a high-fat diet with Cocus nucifera oil
in Wistar rats. Material and Methods: Identification of the chromatographic profile of
the formulations by Gas Chromatography coupled to Mass Spectrometry (GC-MS) and
High Performance Liquid Chromatography (HPLC-UV/Vis). Evaluation of the
antidyslipidemic activity of the nutraceuticals Ormona® SI (OSI), Ormona® RC (ORC)
by induction of saturated fat and subsequently biochemical analysis of the serum of
the animals in the experiment, verification of the presence of atheroma of the animals'
aortas by Scanning Electron Microscopy (SEM), evaluation of possible mechanisms of
action by in silico study. Result and discussion: GC-MS analysis showed Bixa
orellana oil granules with 42.5%, with 10% tocotrienols (mainly the δ isomer) and 28%
geranylgeraniol. The isoflavone-rich fractions (20.8%) of soybean germ (Glycine max)
in Ormona® SI (OSI), or red clover (Trifolium pratense) in Ormona® RC (ORC), in
addition to the standardized açaí extract (Euterpe oleracea, 10%). Experimental results
demonstrated abnormal levels of TC, TG, LDL and HDL caused by a high-fat diet,
increased glucose levels, hepatotoxicity, nephrotoxicity and atherogenesis, however
treatments with nutraceuticals (OSI) and (ORC) were able to reduce these parameters
significantly, thus contributing to the antiatherogenic action. The treatments inhibited
the formation of atheromatous plaques in the vascular endothelium of treated rats, as
well as those treated with simvastatin. It was possible to investigate possible metabolic
pathways through in silico studies using software such as PASS and molecular
anchoring of isoflavones involved in reducing cholesterol. Conclusion: Nutraceuticals
significantly improved all conditions, with results similar to the group treated with
simvastatin. Notably, groups treated with Ormona® or simvastatin + Ormona® had
better liver protection than those treated with SG or simvastatin alone; Furthermore,
nutraceuticals could prevent atherogenesis, unlike SG. The results indicate high
effectiveness of nutraceuticals in preventing dyslipidemia and its complications.

Introduction: Disease outbreaks threaten aquaculture sustainability. Many chemotherapeutics currently used are nonspecific being harmful to farmed individuals, consumers, and the environment. Recently, green and low-cost alternatives such as plant natural products have earned a seat in controlling aquaculture diseases. Among them, terpenoids - constituents of plant essential oils (EO) - stand out. However, their low water solubility poses a technological challenge for their use in aqueous medium. Therefore, developing nanostructured systems becomes a viable alternative to improve this characteristic. Objectives: This study aimed to obtain a nanoemulsion based on Pectis elongata EO with antibacterial and anthelmintic activities for use in pisciculture. Methods: Nanoemulsion was obtained by adopting a low-energy approach, and their physical characteristics were analyzed through dynamic light scattering. The phytochemical profile of EO and nanoemulsion was characterized through gas chromatography. Pathogenicity tests in Colossoma macropomum were performed using the Aeromonas hydrophila standard strain. The effectiveness of nanoemulsion and EO was compared by in vitro tests: antibacterial using standard and isolated strains of A. hydrophila; and anthelmintic using gill arches of C. macropomum parasitized with monogeneans. Results and discussion: The low-energy approach was efficient in creating a nanoemulsion whose droplet average size was 116.4 nm, and polydispersion index (PDI) around 0.215. The droplet size increased from day 30, but, the PDI decreased, suggesting a better homogeneity of droplet size population. The system did not show creaming or phase separation. The nanoemulsification did not change the phytochemical profile of EO, and both had around 90% citral content with the same rate of isomers. The pathogenicity tests showed that the A. hydrophila standard strain has the virulence factors able to infect the C. macropomum juveniles. The antibacterial tests revealed that only the isolated strain was sensitive to tested treatments, and the minimal inhibitory concentration (MIC) of nanoemulsion and EO was 187.5 mg/L and 250 250mg/L, respectively. In the anthelmintic tests, we observed that nanoemulsion has higher activity when compared to EO at the highest concentration. Conclusions: The nanoemulsion showed satisfactory physical stability, and the nanoemulsification did not change the citral rate. The biological assays suggest better biological potential for nanoemulsion at some concentrations. This study opens good perspectives to new prototypes and assays in vivo of P. elongata EO in aquaculture.

Introduction: The variability of vegetable oils results in different applicability, as they have biological properties of great value for the economic, technological and nutritional sector, promoting the interest of these Amazonian natural resources. Numerous plant species produce oilseeds, among them, the species Abelmoschus esculentus L. Moench, Euterpe oleracea Martius and Bixa orellana Linné, which present chemical characteristics and activities pharmacological potential. Objective: To evaluate the effects of the treatment of oils from A. esculentus (OFAE), E. oleracea (OFEO), B. orellana (OFBO) and granules (Chronic SM®) on metabolic syndromes, especially dyslipidemia induced by Cocos nucifera L and alloxan-induced diabetes in wistar rats. Material and Methods: The identification of the chromatographic profile of the oils of the species under study and granulated by gas chromatography coupled to mass spectrometry (GC-MS); evaluation of the antidyslipidemic activity of the oils and granules by induction with saturated fat (GSC) and subsequent biochemical analysis of the animals' serum; verification of the presence of atheroma in the animals' aortas by Scanning Electron Microscopy (SEM); assessment of antiglycemic activity by induction with alloxan; glucose tolerance test (GTT) and subsequent biochemical analysis of the serum of the animals in the experiment; observation of possible histopathological changes in the liver of hypercholerolemic animals and pancreas in diabetic animals after treatment with oils and granules. Results and discussion: The chromatographic profile showed the majority of unsaturated, poly and monounsaturated fatty acids in both oils. The quantification of tocotrienols and geranylgeraniol was obtained in OFBO and CHR. GCS-induced dyslipidemia caused hypercholesterolemia, hypertriglyceridemia, increased levels of low-level lipoprotein (LDL) and atherogenesis in the aorta. However, treatments with OFEO, OFAE, OFBO and CHR were able to significantly reduce glycemia with p>0.001, as well as hypertriglyceridemia, total cholesterol (TC) and LDL, in addition to increasing highintensity lipoprotein (HDL), contributing thus for the antiatherogenic action. The treatments inhibited the formation of atheromatous plaques in the vascular endothelium of treated rats, as well as those treated with simvastatin. In the evaluation of antidiabetic activity, treatments performed with OFEO, OFAE, OFBO and CHR were able to significantly reduce p>0.001 hyperglycemia and glycosuria, as well as being able to decrease triglycerides and lipid profile. The oral glucose tolerance test (OGTT) also showed activity in the glycemic regulation of the treatments. In the histopathological analyzes of the pancreas, a possible regenerative effect of the islets of Langerhans was observed when compared with the control group.

Introduction: Epigallocatechin-3-gallate (EGCG) is a natural polyphenol, extensively found in green tea, which has several therapeutic properties, such as: antioxidant, antienzymatic and chemoprotective. However, its therapeutic use is limited due to its instability and low bioavailability. Zein is a biopolymer capable of carrying bioactive molecules, improving their stability, promoting controlled release and boosting their biological activities. Objective: To develop and characterize EGCG-loaded zein nanoparticles (ZNp-EG) and determine their effects on biological targets related to skin protection and reconditioning. Material and Methods: ZNp-EG were prepared using the nanoprecipitation method, morphologically evaluated by transmission and scanning microscopy and characterized in terms of size, zeta potential, polydispersion index, pH, encapsulation efficiency (EE), drug loading (CF) and release. Finally, the association between zein - EGCG was simulated by molecular docking and evaluated by fourier transformed infrared (FT-IR), fluorescence and NMR spectroscopy. In order to assess its biological potential, the antioxidant activity (ABTS and DPPH), antityrosinase, anti-elastase, anti-collagenase, anti-hyaluronidase and sun protection factor (SPF) were evaluated. Cytotoxicity was evaluated through hemolytic activity, and by MTT and NRU methods against immortalized human keratinocyte cells (HaCaT) and human squamous cell carcinoma cells (A431). Results and discussion: The ZNp-EG showed an average size of 251.8 nm, EE and CF up to 98.43% and 28.35%, respectively. The ZNp-EG in the highest concentration were stable for 365 days under different storage conditions (25 ± 2 ºC / 5 ± 2 ºC). The interaction between zein and EGCG, simulated by molecular docking, was confirmed by FT-IR, steadystate fluorescence and 1H NMR. Both the ZNp-EG and the EGCG solution mantained after 48h a high antioxidant activity by the ABTS method, with IC50 of 84.08 and 69.86 µg / mL and by the DPPH method, with IC50 of 8.26 and 12.34 µg/mL, respectively. The EGCG nanoencapsulation enhanced its anti-tyrosinase (64.59%), anti-elastase (94.08%) and anti-hyaluronidase (22.09%) activities compared to EGCG in solution (34.29, 74.02 and 13.03 %, respectively) under the same conditions, in addition to inhibit moderately collagenase (44.44%). Those results corroborate with the molecular docking observations. BZNp, ZNp-EG and EGCG at the highest concentration tested, showed SPF of 26.13, 30.00 and 26.18, respectively. Finally, BZNp and ZNp-EG did not cause hemolysis and their incorporation into zein nanoparticles significantly reduced the cytotoxicity of EGCG against the cell lines studied. Conclusions: In view of the results obtained, the encapsulation of EGCG in zein nanoparticles was found suitable, improving important biological activities, being a promising strategy for pharmaceuticals and/or cosmetics used for protection, conditioning and regeneration of the skin.

Introduction: Currently, concerns related to aging include cognitive, ocular, bone, joint, cardiovascular and reproductive functions. In order to improve the quality of life, the Brazilian company Ages Bioactive Compounds Co., eveloped the nutraceuticals Chronic®  (CHR), Ormona® SI (OSI) and Ormona® RC (ORC), which have in their formulations bioactive components such as isoflavones, carotenoids, tocotrienols, geranylgeraniol and anthocyanins. However, in the case of OSI and ORC, due to the presence of phytoestrogens, for pregnant and lactating women the use of these nutraceuticals is not being recommended. Objective: to study the effects of the use of these new nutraceuticals during the stages of reproductive development in animal species, rodents and non rodents. Material and Methods: The protocols used in this study are established by regulatory agencies (ANVISA, OECD). In zebrafish, acute and reproductive toxicity was evaluated at doses of 500, 1,000 and 2,000 mg/kg, through the observation of behavioral changes, lethality and tissue changes (intestine, liver, kidney, and sexual gonads). The results obtained in the different analyzes were expressed (mean ± SEM), Kruskal-Wallis test, followed by Dunn's post hoc test (p <0.05). In rodent species, young rats were used, divided into critical periods of development, with five experimental groups (n=4), Polysorbate (POL, 1ml), Lecithin (LEC, 5%/kg), CHR, OSI and ORC (200mg/ kg, respectively). He critical periods of development were pre-implantation (d0-d5), post-implantation (d6-d15) and postnatal (dpn13-dpn19), evaluating acute toxicity, water intake, food intake, weight development and reproductive performance, hormone dosage for thyroid markers, dosage of biochemical markers, in addition to macroscopic and microscopic analysis of vital and reproductive organs. The results obtained in the different analyzes were expressed (mean ± SDM), ANOVA, followed by the Tukey test (p < 0.05). All analyzes were performed using the GraphPad Prism® software (5.03). Results and discussion: Treatment with OSI and ORC in zebrafish caused a decrease in fertility, and this effect was also reproduced in rodents, in the pre-implantation period, suggesting a reduction in reproductive capacity and implantation of blastocysts in the uterus. In the post-implantation test, treatment with CHR, ORC and OSI, for ten days, provided fetal development without abnormalities, mainly in the ossification and visceral process of the offspring. In the postnatal period, no toxicity was observed in lactating females or in their descendants, being observed that the treatment with CHR, OSI and ORC, responsible for the significant decrease of the plasma concentration of the lipid profile. Treatment for seven days with CHR, OSI and ORC did not trigger signs of behavioral or physical alterations in the evaluated parameters of the offspring. Conclusions: The presence of isoflavones in Ormona® formulations (OSI and ORC) caused negative effects on the decidualization process, increasing the occurrence of pre-implantation losses in young female rats. However, the results show that the lactation CHR, OSI and ORC were safe for lactating animals and their offspring for all evaluated parameters.

Introduction: Plant-derived products are promising agents in the treatment of various diseases. The species Trattinnickia rhoifolia (Willd), (T. rhoifolia), belonging to the Burseraceae family, is present in the cultural practices of ethnomedicine and ethnopharmacology of the Peoples and Traditional Communities (PCTs) of the  Brazilian Amazon and is used for anti-inflammatory purposes, sometimes as the only therapeutic resource. Despite this, the species is still unexplored in its pharmacophoric potential. Therefore, the objective of this study was to evaluate the acute toxicity and anti-inflammatory action of the hydroethanolic extracts of leaves (HELTr) and resin (HERTr) of the species T. rhoifolia with non-target organism zebrafish (Danio rerio). In Methodology, the extracts were analyzed by gas chromatography coupled to mass spectrometry (GC-MS). The assessment of the acute toxicity of HELTr and HERTr in adult zebrafish was determined using the Limit Test (2000 mg/kg), with behavioral and histopathological assessments, in addition to the analysis of anti-inflammatory potential in carrageenan-induced abdominal edema, followed by use of the computational method of molecular docking. The chemical-pharmacological profile of the species showed the presence of propanoic acid, ethyl ester; hexadecanoic acid, ethyl ester; 2-methyl 1-propanol; propane, 2,2-diethoxy; n-hexadecanoic acid; n-propyl acetate; benzophenone; propane,1,1,3-triethoxy; 1-butanol, 3-methyl; acetic acid ethenyl ester; decanoic acid; ethyl ester; 3-hydroxybenzoic acid. In studies with zebrafish, HELTr and HERTr did not show toxicities in behavioral and histopathological assessments, according to the IAH, as there was no change in the functioning of the organs studied. Carrageenan-induced abdominal edema, at all doses of HELTr and HERTr, (100, 200 and 500 mg/kg), were significantly reduced in relation to the negative control (DMSO), whereas the doses of 200 and 500 mg/kg were significantly reduced. kg showed expressive anti-inflammatory activity in relation to the positive control (indomethacin) of the tested extracts. As the activities were confirmed by molecular docking studies, they showed a high profile for the inhibition of the Cyclooxygen-nase-2 enzyme, since the interactions established in the receptors used in the docking study were similar to the controls used. HELTr and HERTr had an acceptable degree of safety for acute toxicity, defined in the analysis of behavioral changes, mortality and histopathology, with significant anti-inflammatory action in zebrafish at all doses, which demonstrates the high pharmacological potential of the species.

Brazil is a country with great biodiversity, being considered one of the largest in the world. Medicinal plants have been used since the dawn of humanity, being inserted in the treatment of various pathologies. Essential oils are made up of volatile substances from the secondary plant metabolism of aromatic plants. They are formed in special cells found in different parts of plants such as leaves, flowers, seeds, stems and roots. The objective of this work is to obtain and chemically characterize the essential oil of the Protium heptaphyllum resin and test the cream emulsions and nanoemulsions prepared with the essential oil and evaluate the biological activities: ovicidal, pupicidal, larvicidal, residual and repellent against Aedes aegypti. The essential oil was extracted by the steam drag technique in a Clevenger apparatus and characterized by Gas Chromatography coupled to a Mass Spectrometer. The nanoemulsion was prepared by a low energy titration method and characterized by photon correlation spectroscopy. The cream was prepared by the phase inversion temperature technique. The protein odor inhibition potential in Aedes aegypti and Anopheles gambiae was evaluated by molecular docking (MD) simulations. The extraction yielded 0.69 ± 0.085 (m/v) of essential oil. In the chromatographic analysis, the major constituents were p-cymeno (27.70 %), α-Pineno (22.31 %). The zeta potential demonstrated a kinetic stability and a monomodal distribution in the hydrophilic-lipophilic balance 14 with a particle diameter of 115.56 ± 1.68 nn and a zeta potential of -29.63 ± 3.46 mV. In the larvicidal trial, the group treated with the nanoemulsion at 20 µg.mL-1 reached 96% mortality in the first 24 hours, reaching 100% in 48 h. In the residual test, concentrations of 20 and 40 µg.mL-1 showed mortality up to 3 days, while doses of 60, 80 and 100 µg.mL-1 showed mortality up to 11 days, the control groups had no mortality. The nanoemulsion showed insecticidal action with LC50 0.404 µg·mL−1 for the ovicidal effect. In the pupicidal test, the concentration of 160 µg·mL−1 showed 100% mortality after 24 h of test. In adulticidal activity the diagnostic dose of 200 µg·mL−1 was determined in (120 min). In the repellency test, the concentration of 200 µg·mL−1 during the 180 min of the test showed a protection index of 77.67%. In molecular docking, the control showed significant stability and a proven repellent action. The α-Phellandrene and 2-Carene molecules showed a dual effect of action for the inhibition of AgamOBP1 (PDB ID 3N7H) and AaegOBP1 (PDB ID 3K1E. Therefore, the results presented here suggest that the essential oil emulsions of the Protium heptaphyllum resin have great potential in the prevention and control of Aedes aegypti.

Introduction: Endophytic fungi represent a rich source of bioactive natural products still unexplored. Its secondary metabolites are particularly attractive due to the metabolic interactions with their hosts. Arboviruses, mainly those transmitted by Aedes aegypti, are considered a public health problem, especially because vaccines are not yet available, and vector control is the most efficient way to contain outbreaks caused by these viruses. In this regard, vector control through effective and selective substances with low human and environmental toxicity is essential. Objective: This work aimed to obtain extracts of endophytic fungi isolated from Bertholletia excelsa and evaluate their larvicidal potential against Aedes aegypti, as well as elucidate a possible mechanism of action of the substance in the insect's nervous system. Methodology: Endophytic fungi were isolated from Bertholletia excelsa nuts. Different extracts and growing medium were prepared (liquid and semi-solid). Then the extracts were dried, characterized, and evaluated against the 3rd instar larvae of Aedes aegypti under controlled laboratory conditions, at different concentrations and medium. Possible mechanisms of action and inhibition of acetylcholinesterase and juvenile hormone were evaluated through computational methods such as molecular docking for 187 molecules cataloged in the literature as metabolites of the fungus Aspergillus sp. Result: The isolated fungi were molecularly identified as Aspergillus sp and Trichoderma asperellum. The extracts tested on Aedes aegypti showed, in general, high to moderate bioactivity. The hydroethanolic extract of Aspergillus sp revealed LC50 values of 26.86 μg/mL in 24 hours and 18.75 μg/mL in 48 hours. Through molecular docking, the compound Aspergillol B, present in this extract, was identified as a potent larvicidal candidate for inhibiting the enzyme acetylcholinesterase. From the 187 substances produced by the fungus Aspergillus spp, the validation results of the molecular docking protocol indicated that N-βacetyltryptamine presents itself as a potential insecticidal agent that inhibits the action of juvenile hormone. The crude extract of the fungus Trichoderma asperellum, when evaluated on Aedes aegypti, revealed promising results for vector control when associated with silk protein as a vehicle, in addition to the absence of significant toxicity to non-target organism Danio rerio. Conclusion: This study allowed the isolation, identification, and production of extracts of endophytic fungi, Aspergillus sp and Trichoderma asperellum from Brazil nuts and their larvicidal evaluation in Aedes aegypti. Moreover, it elucidated possible mechanisms of action of substances produced by them. New substances have been identified as potential insecticide candidates, such as Aspergillol B, which may represent significant advances in the control of vectors with toxicological safety.

Introduction: Cyclooxygenase 2 (COX-2) selective non-steroidal anti-inflammatory drugs were designed to avoid or even decrease the incidence of side effects of cyclooxygenase 1 (COX-1) inhibition. Cyclooxygenase 2 (COX-2) is an enzyme that acts as a target for the design of anti-inflammatory intermediates. Celecoxib was selected as a reference molecule to perform ligand-based virtual screening, in the search for structures with similar shape and electrostatic potential. Objective: The aim of this study was to design new cyclooxygenase 2 inhibitors with potential antiinflammatory activity from celecoxib through a bioinformatics approach. Material and methods: Virtual screening strategies were performed based on the ligand celecoxib, by searching for structures by similarity in the form of the Rapid Overlay of Chemical Structures (ROCS) “Top2000/base” and electrostatic potential of the Electrostatic Similarity calculations (EON) “ Top500/base” in eight commercially available databases, as well as ChemBridge (DIVERSet TM_ EXP), DIVERSet CORE Library (DIVERSet™-CL), ZINC drug database, ZINC natural stock, Drug@FDA BindingDB, IBS Natural subdivision, IBS Synthetic subdivision and Princeton. Afterwards, the pharmacokinetic predictions were screened using the QikProp program and the toxicological predictions filtered through the Derek and ProTox software. There was molecular coupling and refined based on affinity value and binding energy as standard template ligand celecoxib and rofecoxib. Afterwards, predictions were made on the Molinspiration server and in silico analysis of endocrine disruption. Then, the selected molecules follow the metabolism predictions and molecular dynamics simulations. Results and discussions: The search for structures based on the stereo-electronic space resulted in 4000 molecules that followed the pharmacokinetic screening, where a total of 2,702 and toxicological 947 structures were obtained, so that, after molecular docking, it happened in 2 structures. Conclusions: In molecular docking, there was higher binding affinity compared to rofecoxib on the COX-2 target for theoretical data. In predicting bioactivity, ZINC408709 and ZINC2090319 were considered biologically active. In the endocrine disruption analysis, it was established that the molecule ZINC2090319 strongly binds to the target related to cardiovascular risk in a desirable manner as a non-steroidal antagonist and ZINC408709 is associated with the treatment of inflammatory diseases similar to celecoxib. The metabolite generated in this theoretical study is less likely to have adverse effects. Despite the differences, the ZINC408709 molecule showed better stability for COX-2 during molecular dynamics simulation.

Brazil is a country with great biodiversity, being considered one of the largest in the world. The objective of this work is to prepare a cream containing the essential oil of Ocimum basilicum, evaluating its accelerated stability and evaluation of the repellency test against the Aedes aegypti mosquito. Ovicide, larvicide, pupicidal and adulticide tests were performed. The main chemical constituents were Linalool (36.90%), Eucalyptol (9.95%), Estragole (7.57%), α-Bergamotene (6.67%) and τ-Cadinol (6.18%). The essential oil showed insecticidal action with LC50 73.5 μg.mL-1 for ovicidal activity, LC50 89.5 μg.mL-1 for larvicidal activity and LC50 816.5μg.mL-1 when evaluating the pupae. With regard to adulticidal activity, all concentrations tested showed activity. As for the residual evaluation, the oil showed that the concentrations of 100, 200 and 300 μg.mL-1 showed longer lasting responses than the other concentrations tested. The larvae, exposed to the oil of the species, showed changes in their morphology when compared to the control. Stability was evaluated in the following physicochemical parameters: temperature (environment, refrigerator and oven), centrifuge, pH and organoleptic characteristics. During the study, the organoleptic characteristics remained constant. The pH did not change. At room temperature and refrigerator there was no change. In the centrifuge and oven analysis, there was no phase separation and the organoleptic characteristics remained the same. The repellency test of the cream and essential oil showed a protection index of 97% and 95.67% in the 30 minutes after its application and in the time of 180 minutes it protected approximately 85% and 81%. The findings corroborate the potentiality of the species against the A. aegypti vector. In conclusion, O. basilicum cream can be considered a promising agent for the control of infectious disease vectors.

Portulaca pilosa L., belonging to the Portulacaceae family, is a herbaceous plant that is traditionally used as an aid in the treatment of burns, insect bites and wound healing. Objective: This study aimed to evaluate the anti-inflammatory, gastroprotective and healing activities of P. pilosa extract (EPP) in Wistar rats. Methods: surgical wounds were made in the dorsal region for the healing activity and treated topically for seven days. After treatment, a sample from the treated area was removed, and histopathological analysis was performed. For the anti-inflammatory activity, granuloma and paw oedema tests by carrageenan were used. The gastroprotective effect was evaluated in a stress-induced gastric injury model in Wistar rats. Results: The EPP significantly modulated the tissue inflammatory response, showing a low number of inflammatory cells in the histopathological study. Treatment with PPE significantly stimulated angiogenesis, and this response was superior to the fibrinase^® group. Treatment with EPP significantly stimulated fibroblast proliferation, indicating great healing potential. In the gastroprotection study, previous oral treatment with PPE (300 mg/kg) showed the presence of type 1 lesions and abundant presence of mucus adhered to the gastric wall significantly (p < 0.01) when compared with the negative control group, the results showed evidence of gastroprotection. Tests on inflammation models showed that treatment with PPE was able to reduce the inflammatory process significantly. In the phytochemical study of EPP using ¹H NMR and ¹³C-APT and LC-DAD-MS / MS, eight diterpene compounds were identified: Pilosanol C, Pilosanol B, Pilosanol A, Pilosanone B, Porwenin B, Pilosanone A, Pilosanol D and Porwenin C. Furthermore, the presence of phenolic compounds, mainly gallic acid, was confirmed. Such compounds have great pharmacological potential. Conclusion: According to the experimental conditions, it can be evidenced that the EPP presented anti-inflammatory, gastroprotective and healing activities against the models used, and these activities may be related to the diterpenic and phenolic compounds present in the P. pilosa species.

Introduction: Leukemia is a malignant disease of the white blood cells, usually of unknown origin. Leukemic cell infiltration occurs through the hematogenous route, and treatment is carried out through pharmacotherapy with drugs whose main objective is the destruction of cancer cells. Objective: The aim of this work is to identify new drug candidates through bioinformatics techniques, based on virtual screening based on ligand and structure. Methodology: Initially, seventeen (17) structures were selected (based on inhibitory activity values , IC50) and the structure with the lowest value was chosen as the pivot (IC50=0.6nm). Two optimizations were performed in the MM+ and Am1 method in order to compare the energies of optimizations, with each method a pharmacophoric model was obtained from the online PharmaGist server. The pharmacophoric characteristics of both optimizations were statistically evaluated using Pearson and Pearson correlations. chemometric analysis. The models were submitted to ZincPharmer and Pharmit servers. The compounds obtained were compared to pivot, being the most promising, evaluated the ADME /TOX properties and biological activities for the first optimization method (MM+); for the second optimization (AM1) similar approaches were performed and additionally molecular homology studies followed by molecular docking. Results: the results of the virtual screening were possible to select 08 (eight) structures, five from the first screening ZINC72088291, ZINC68842860, ZINC14365931, ZINC09588345 and ZINC91247798 and three from the second screening MolPort-000-670-224, MolPort-007-574- 861 MolPort-001-674-278. The compounds with promising activities showed satisfactory pharmacokinetic and toxicological profiles. Conclusions: The selected structures presented similar or superior properties to the pivot structure and were considered in this study as promising for the potential anti-cancer activity, however, future studies are still needed to confirm the potential antitumor activity of the molecules selected in this work with in vitro assays and in vivo.

Introduction: Cannabis sativa L. is a plant known by several popular names, such as: "Marijuana", "Maconha" and "Hemp". It belongs to the Cannabinaceae family. Cannabis sativa has been described in many studies as being one of the first plants to be cultivated by man, dated at least 12,000 years ago. Its medicinal properties have been studied for centuries, however, C. sativa is still a source of great wealth for pharmacological studies. Objective: Thus, this work aimed to carry out a vast bibliographic review, to develop nanoformulations with the fixed oil of C. sativa (OCS) and to carry out pharmacological studies in Wistar rats in order to demonstrate the anti-inflammatory, anti-diabetic and anti-hyperlipemic properties. Methodology: Initially, the development of the nanoemulsion of the C. sativa oil (NCS) was carried out, then the anti-inflammatory activity of the OCS and NCS was evaluated, against the inflammation models produced by the Bothrops moojeni venom. (VBm). Rat paw edema was induced by VBm (0.10 mg / kg), peritonitis and analysis of leukocyte infiltrate in the muscle and formation of granulomatous tissue. Then, the action on diabetes (DM) and dyslipidemia induced in Wistar rats with streptozotocin (STZ) and Triton (tyloxapol), respectively, was evaluated. Results and discussions: 18 nanoemulsions were produced, the characterization and stability revealed that the formulations showed stability with particle sizes ranging from 275.6 ± 5.57 to 129.3 ± 0.15 nm and polydispersity index between 0.25 ± 0.014 to 0.22 ± 0.019. In the toxicological evaluation, OCS and NCS showed low toxicity after acute oral administration, with an LD50 greater than 2000 mg/kg. The 500 mg/kg doses of OCS and NCS for 28 days of subacute treatment did not produce toxicity. The treatments with OCS (200 and 400 mg/kg) and NCS (100 mg/kg) were able to significantly inhibit (p < 0.001) the inflammatory process in all models employed. In the induction of DM by STZ, it was possible to reproduce the characteristic clinical signs and symptoms, such as polyuria, glycosuria, hyperglycemia and hyperlipidemia. Treatments with OCS and NCS produced a significant increase (p < 0.05) in insulin levels in animals with DM, and in dyslipidemia, it was observed that treatments with OCS and NCS significantly decreased triglyceride levels (p < 0.05), cholesterol (p < 0.001) and LDL (p < 0.01). Conclusions: The treatment with OCS and NCS in the conditions of this study, demonstrated anti-inflammatory, anti-diabetic and anti-hyperlipemic effects acting on the levels of triglycerides, cholesterol and LDL. In this regard, it contributes to the control of DM, acute and chronic inflammatory processes and as a preventive agent of cardiovascular diseases.

Introdução: O tratamento endodôntico visa combater uma inflamação e/ou infecção pulpar que pode resultar na colonização bacteriana de todo o sistema de canais radiculares incluindo os túbulos dentinários. O microrganismo Enterococcus faecalis tem sido a espécie mais prevalente em casos de falha e retratamento endodôntico, sendo resistente ao preparo químico-mecânico e a maioria dos medicamentos utilizados. O ácido anacárdico apresenta propriedades antibacterianas importantes. A sua nanoencapsulação poderia melhorar os seus aspectos biofarmacêuticos, aperfeiçoando o seu uso terapêutico. Objetivo: O presente trabalho teve como objetivo avaliar a efetividade de nanopartículas de ácido anacárdico na desinfecção dos canais radiculares ex-vivo sob a forma de curativo endodôntico intracanal e na redução da infiltração bacteriana pós-tratamento endodôntico. Metodologia: Foi utilizado um modelo ex-vivo utilizando espécimens radiculares obtidos de dentes humanos (n= 66) para verificar a redução na viabilidade microbiana do biofilme de Enterococcus faecalispré-formado no interior do canal radicular. Após a contaminação, os dentes foram submetidos a um dos 5 tratamentos pré-estabelecidos: 1. Nanopartículas de zeína contendo ácido anacárdico (9,375 µg/ml) (AAN), 2. Digluconato de clorexidina 2% (CHX), 3. Nanopartículas brancas de zeína (BN); 4. Soro fisiológico com bactéria (SSB); 5. Soro fisiológico estéril (SS). Em seguida, foram coletadas amostras do interior dos condutos para avaliar a viabilidade bacteriana em termos de unidades formadoras de colônia (CFU)/ml, após 7, 14, 21 e 30 dias

, sendo alguns espécimens de cada grupo seccionados e apreciados quanto a presença e característica do biofilme formado no seu interior. Para avaliar o efeito na infiltração bacteriana pós-obturação endodôntica, espécimens radiculares bovinos (n=60), inseridos em um dispositivo confeccionado para este estudo, foram submetidos a um dos 6 tratamentos, sendo em seguida obturados com... e por fim inserido o inóculo de E. faecalis. A infiltração bacteriana foi avaliada diariamente por meio da turvação do meio de cultura estéril contido na parte inferior do dispositivo por um período de 21 dias. Os dados obtidos foram tabulados e submetidos à análise estatística comparativa entre os grupos. Resultados e discussão: Na avaliação da desinfecção, observou-se que o grupo tratado com AAN apresentou redução aos 14 dias de estudo. No grupo tratado com CHXS, houve redução significativa no dia 14, no entanto, no dia 21 houve um grande aumento do número de UFC. O grupo das nanopartículas brancas, apesar de não apresentar efeito antimicrobiano, reduziu o número de UFC possivelmente por atuar como uma barreira física impedindo a profileração do biofilme bacteriano. Na avaliação da infiltração bacteriana pós-obturação, cerca de 82% dos espécimes apresentaram infiltração bacteriana antes dos 21 dias. Conclusões: Deste modo, foi comprovada a eficácia das formulações testadas a partir da nanoencapsulação do ácido anacárdico no combate a um dos microrganismos mais resistentes ao tratamento endodôntico. As nanopartículas utilizadas mostraram-se eficazes após 7 dias e alcaçaram um efeito semelhante a clorexidina após 14 e 21 dias, podendo ser utilizadas como alternativa aos curativos endodônticos, sempre e quando exista a necessidade de maior tempo interconsulta. Estas formulações, poderiam ainda ser testadas concomitantemente à este agente para reduzir a sua dose e também os seus efeitos adversos. Em relação a infiltração bacteriana, os achados sugerem que nenhuma dos  tratamentos utilizados foi capaz impedir a infiltração bacteriana após 21 dias.

Introduction - Cassia grandis L.f is a medicinal species used by several populations of Central America, the Caribbean, and South America, especially in Brazil. The fruits have shown utility to treat digestive diseases, anemia and as an antidiabetic. Although the plant has been used for centuries, no studies of its toxicity, its usefulness as a hypoglycemic agent, nor studies of pharmaceutical formulations developments using this plant or its extracts have been performed. Objectives In this study the physical, chemical, pharmacological and toxicological characterization of the Cassia grandis fruit extract (CgE) was performed. The formulation and characterization of a nanodispersion with hypoglycemic activity was also carried out. Materials and Methods- The preparation of CgE was done by maceration using 70% ethanol. The qualitative and quantitative chemical composition of CgE was evaluated. The evaluation of acute and subacute oral toxicity and the antioxidant and hypoglycemic activity of CgE were performed. The inhibitory effect of pancreatic lipase and alpha-glucosidase were evaluated as the possible mechanisms involved in the hypoglycemic effect of CgE. Subsequently, it was developed a Cassia grandis extract nanodispersão (CgND). The physicochemical characterization and the stability evaluation of CgEN it was performed. Finally, it was made the hypoglycemic activity evaluation of CgND. Results and discussion- CgE contain phenols, flavonoids, coumarins, saponins, and terpenoids. The extract presented a potent hypoglycemic effect in the pharmacological model employed, probably due to antioxidant mechanisms and inhibition of the enzyme alphaglucosidase (IC50=32,30 ± 1,30). CgE did not show acute oral toxicity (2000 mg / kg) or subacute (1000 mg / kg) for 28 days in Sprague Dawley rats. CgND presented particle size lowest of 110 nm, and an excellent physical and chemical stability during one year. The CgND presented a hypoglycemic and inhibitory effect of pancreatic lipase (IC50=0,58 ± 0,02).The antioxidant potential of CgND was higher than the CgE. From the results here obtained, we can suggest that the mechanisms involved in reducing the blood glucose levels of CgND occur via antioxidant, and via alpha-glucosidase inhibition, which is probably enhanced by the slower release of the active substance from the nanoparticles. Conclusions- From the results obtained, we suggest that the pharmaceutical formulation here obtained is stable, and has a potent hypoglycemic activity, arising as a promissory formulation to be employed as an adjuvant in the diabetes treatment.

Introduction: Acmella oleracea L., is a plant species widely used in the north of Brazil in the treatment of various diseases such as tuberculosis, influenza, cough, rheumatism and especially in popular medicine as a female aphrodisiac. The extract of flowers and aerial parts has been used in pharmacological studies which attribute their activities to spilanthol, mainly as a sexual stimulant. However, there was no record of studies demonstrating the action of this plant or spilanthol on reproductive performance in laboratory animals and zebrafish (Danio rerio), which has already been established as a model for several toxicological studies. Objective: To evaluate the acute and reproductive toxicity of the hydroethanolic extract of the flowers of Acmella oleracea (EHFAo) and spilanthol in vivo assays and to study the pharmacological and toxicological in silico mechanisms. Methodology: EHFAo and spilanthol were used in oral zebrafish (48 h) orally and immersion in the following doses and concentrations 44.457, 88.915, 199.53, 281.83, 448.81 mg/kg and 250, 300, 350, 400 e 450 μg/l, respectively. The behavioral, mortality and histopathological analyses were performed in the adult animal, and the acute toxicity test in the embryo (96 h), with evaluation of the lethal and teratogenic effect (0.1, 0.25, 0.5, 0.75, 1.0 and 1.5 μg/ml); and reproductive toxicity (21 days), with fertility evaluation, histopathology of the gonads and lethal and teratogenic effect in F1 generation. Results: The phytochemical analysis of EHFAo confirmed the presence of spilanthol as the major compound in EHFAo. EHFAo and spilanthol showed toxicity in the adult zebrafish and oral embryo and immersion, evidenced by significant behavioral changes, mortality and histopathological analysis, as well as changes in the development of embryos at higher doses. In the reproduction, the animals treated by immersion presented spawned spawn and high rates of malformations; in the orally treated animals, spawning was significantly inhibited, and malformations were more evident in embryos whose parenting was orally treated with EHFAo and the mortality in the embryos that parental generation was treated with spilanthol. Conclusion: The present study confirmed that EHFAo and spilanthol have a toxic action on the adult zebrafish and embryo and that when these animals were treated with the EHFAo by immersion, they produced an increase in spawning, while spawning was inhibited when treated orally with either the EHFAo and spilanthol. However, in the in silico study, it was shown that the metabolism of spilanthol does not cause changes in embryonic development. Therefore, this study collaborates with the toxicological validation of this plant species and its products.

Introduction: The pharmaceutical market offers resources and technologies to the aid and treatment of the healing processes, but many products have severe adverse effects, and are costly. In Brazil, the Curatella americana species is traditionally used for the treatment of wounds, ulcers, and inflammation. However, its traditional use in the treatment of wounds has not been validated by scientific studies. Objective: To evaluate the healing potential of the hydroethanolic extract of C. americana leaves (HECA) through in silico, in vitro and in vivo studies. Methodology: Major compounds identified in the species were evaluated via quantum chemical studies, molecular docking and in vitro for antioxidant potential. Liquid chromatography coupled to high resolution mass spectrometry was used to identify the compounds present in the HECA. The extract was evaluated for coagulant, antimicrobial and dermal toxicity activities. For the cicatrizing activity, Swiss mice were divided into the following groups: positive control (FIB - Fibrinase SA ®), negative control (CV - gel vehicle), solution containing lyophilized extract of C. americana 0.5% (CaE 0.5%); solution containing lyophilized extract of C. americana 1.0% (CaE 1.0%), C. americana gel 0.5% (CaG 0.5%), C. americana gel 1% (CaG 1%). After excision of the cutaneous wound, the animals were treated topically twice a day consecutively for 7 or 14 days. Results and discussions: The in síilico studies demonstrated the antioxidant potential of the species confirmed by DPPH. Elucidation by LC-MS revealed 13 phytopharmacos present in EHCa, among them, compounds identified for the first time in the species, such as apigenin-7-O-glycoside, Kaempferol, Kaempferol-3-O-glucopyranoside. Topical application of the extract aqueous solution and the Curatella american 1% gel accelerated the contraction of the excisional wounds in the 7 day period. On day 14, all animals treated with C. americana based formulations had advanced remodeling stage and denser collagen fibers. Conclusions: The present study points out perspectives for the use of EHCa in skin wounds, topically every 12 hours, in the concentration at 1% for 14 consecutive days

Euterpe oleracea Mart. is a plant that presents several composition and biological studies. This work aimed the technological development of formulations containing hydroethanolic dry extract of Euterpe oleracea Mart. (EEEO) and systematically report the use of pharmaceutical technology methodologies through the physical and chemical characterization of the EEEO, which was obtained after an experimental design aiming to obtain a higher content of anthocyanins. The quality control has been done since the collection to the development of the formulations. The selection of the best form of extraction was done through a factorial design. To characterize the EEEO, the specific parameters for plant extracts contained in the Brazilian and American Pharmacopoeias (USP) were used. In addition to the pharmacopoeial parameters, techniques such as thermal analysis, IFTR, atomic absorption spectroscopy, SEM, CCD, HPLC and UV spectrophotometry were used. The nanoparticulate polymer system (SPN) was obtained by the nanoprecipitation method. The characterization involved the determination of pH, particle size, zeta potential, encapsulation efficiency and total anthocyanins. All measured parameters were evaluated against short and long term stress conditions. The tablets were developed and characterized for flow properties, compaction, hardness, friability, desintegration and dissolution profile. Acute oral EEEO toxicity was evaluated. It was observed that the higher amount of acetic acid, the higher total anthocyanins content. The SPN containing EEEO showed good stability and proved to be adequate for prolonging the useful life of anthocyanins from açaí. It was also observed the release of total anthocyanins from the synthetic and biological membrane SPN in a permeation system. The tablet formulation chosen contained 0.11 g of magnesium stearate. The dissolution test showed a tablet with virtually immediate release. No acute EEEO toxicity was observed when administered orally in rats. The EEEO has radical sequestration capacity with IC₅₀ for DPPH of 31.5 ± 2.31 ppm.

Introduction: Dyslipidemia is due to disorders at any stage of lipid metabolism. It causes chronic elevations in serum lipid levels, especially LDL-cholesterol and triglycerides, predisposing the individual to complications such as metabolic syndrome, diabetes, atherogenic processes and cardiovascular diseases (CVDs). The fixed Euterpe oleracea Mart. oil of fruits (OFEO) has been described with a chemical composition rich in unsaturated fatty acids (AGIs), which characterizes it with potential for the treatment of alterations in lipid metabolism. Objective: to investigate the action of OFEO on dyslipidemia in Wistar rats. Method: Male Wistar rats were divided into experimental groups (n = 7/group) to compose three models of induction of dyslipidemia. Model I - Dyslipidemia induced by Cocos nucifera fat (2000 mg/kg, v.o), Model II, Triton-induced dyslipidemia (150 mg / kg, i.p). Model III, dyslipidemia in diabetic rats induced with aloxane (150 mg / kg i.p). In all assays the groups were divided into: treated with OFEO (1226 mg/kg, vo), control groups treated with distilled water (0.5 ml, v.o) and with standard drugs (Sinvastatin, 20 m /kg and Glibenclamide, 5 mg/kg, v.o). Results: The physico-chemical and chromatographic analyzes of OFEO presented a chemical constitution with predominance of UFAs (67.83%), with oleic acid (54.32%) and linoleic (5.90%) being the major compounds. In the models of dyslipidemia employed, there was a significant increase in serum lipid levels, mainly LDL-cholesterol and triglycerides. The groups treated with OFEO in the different experimental models significantly reduced (p < 0.001) plasma triglycerides, total cholesterol and LDL-cholesterol, and significantly increased HDL-cholesterol (p < 0.001). In model I, under the treatment conditions employed, OFEO showed antiatherogenic activity, inhibiting the formation of atheromas in the aorta artery of the animals used. In Model III, OFEO attenuated the biochemical parameters related to the metabolic syndrome, significantly reducing (p < 0.001) hyperglycemia, LDL-cholesterol and triglycerides. Therefore, it is concluded that the treatment with OFEO used in the conditions of this study, presents action on the lipid profile and Anti-atherogenic properties in animals with dyslipidemias, possibly due to the presence of UFAs, so it may contribute to the control and / or as a preventive agent of the CVDs.