Essential oils from Cymbopogon citratus and Lippia sidoides in the anesthetic induction and transport of ornamental fish Pterophyllum scalare.

This study verified the effects of essential oils from Lippia sidoides (EOLS) and Cymbopogon citratus (EOCC) on the anesthesia of freshwater angelfish (Pterophyllum scalare) of two different sizes (juveniles I (0.82 g) and II (2.40 g)) and the transport (8 h) of juveniles II. Fish were exposed to different concentrations of EOLS and EOCC: 0, 10, 25, 50, 75, 100, 150, 200, and 250 mg L-1. Ventilatory rate (VR) and transport for 8 h with 0, 10, and 15 mg L-1 of each essential oil were evaluated in juveniles II. The major components found in EOLS and EOCC were carvacrol (44.50%) and α-citral (73.56%), respectively. The best sedation and anesthesia times for both essential oils were obtained with 10 and 25 mg L-1 and 200 and 250 mg L-1 for juveniles I and II, respectively. Fish sedated with EOLS had lower VR values than the other treatments. Blood glucose levels were higher in ornamental fish transported with 10 and 15 mg EOLS L-1 and 15 mg EOCC L-1. Hepatic glycogen values were higher in the control group. In general, fish transported with 10 mg EOLS L-1 showed fewer gill histological alterations than other transported fish. When the type of lesion was evaluated, the highest gill alterations occurred in fish transported with EOCC. In conclusion, 10 mg EOLS L-1 could be used to transport of juveniles II because although this concentration increased blood glucose levels, it decreased the VR and muscle glycogen levels and caused only mild alterations to the gills.

Phytochemicals and biological properties of Annona coriacea Mart. (Annonaceae): A systematic review from 1971 to 2020.

Annona coriacea Mart., popularly known as "marolo", "araticum" and "araticum-liso" is a species distributed in Paraguay and Brazil, and easily found in Caatinga, Cerrado, and Pantanal biomes. The araticum has been used in folk medicine to treat stomatitis, neuralgia, rheumatism, headaches, furuncle, ulcers, and dermatitis. This systematic review aimed to provide a comprehensive overview of the ethnomedicinal use, phytochemistry, and pharmacological activity of A. coriacea. A search for scientific articles of electronic databases (Science Direct, PubMed, Lilacs, Scopus, Google Scholar, Scielo, and Web of Science) was performed identifying studies published until November 2020. All papers considering traditional medicinal uses, phytochemistry, and pharmacological properties were included. Forty-six articles (n = 212 subjects) met the inclusion criteria set for this review. Of the 46 articles reviewed, 34 were focused on biological activity investigations, while 12 were limited to phytochemical studies. These studies showed the presence of a diversity of secondary metabolites such as acetogenins, sesquiterpenes, alkaloids, flavonoids, and diterpenes. To date, pharmacological tests have demonstrated significant biological activities of this plant, being the most promising anticancer, anti-inflammatory, antiulcer, and insecticide activities. Additionally, the medicinal utilization of A. coriacea appears to be promising, supporting its possible uses for human health with antioxidant, anxiolytic, antiulcer, insecticide, and antiparasitic activities. Ultimately, comprehensive studies involving clinical trials are required to validate the existing traditional practices and their related health benefits scientifically.

Efficacy of essential oils in the management of soft rot caused by Pectobacterium aroidearum in lettuce

Lettuce is susceptible to several diseases, especially soft rot caused by bacteria of the genus Pectobacterium. Due to the adaptability of this pathogen and the lack of disease control registered for the crop, the objective of this work was to evaluate the effects of essential oils in the management of soft rot caused by P. aroidearum in lettuce. The study was developed at the Universidade do Estado da Bahia, Juazeiro, BA, Brazil, and the essential oils (EOs) of orange, bergamot, lemongrass, palmarosa, citronella, cloves, tea tree, rosemary, sage, and ginger were used in concentrations of 0.25; 0.5; 0.75 and 1.0% to assess the in vitro growth inhibition of the bacterium. Subsequently, the curative effects of the disease were evaluated by applying the EOs that obtained the best results in vitro in lettuce plants of the susceptible variety "Mônica". The treatments were applied, via spraying, 12 hours after inoculation using the bite method with bacterial suspension. The best in vivo treatment was selected to assess its preventive and curative activity, as well as to find the ideal concentration for reducing epidemiological variables and chromatographic characterization. The EOs of palmarosa, sage, citronella, lemongrass, and cloves (0.25%), and that of sage (0.75%), inhibited bacterial growth in vitro. The EO of salvia showed the best results in vivo, inhibiting the growth of the disease in concentrations of 0.50 and 0.75%, so it was selected for the preventive and curative control tests alone. The preventive treatment was not efficient for the management of soft rot in lettuce, however, from the regression analysis, a concentration of 0.64% of the salvia EO was found as a potential for curative control of this bacteriosis, as it reduces the incidence and severity of the disease. Linalyl acetate and linalool were found in higher concentrations in the chromatographic analysis. These components, probably, conferred the bactericidal capacity of the EO of sage, being potential for the use in the control of P. aroidearum in lettuce.

Annonaceae Family Alkaloids as Agents Against Leishmaniasis: A Review and Molecular Docking Evaluation.

Leishmaniasis is a neglected disease that affects 15 million people worldwide. Existing treatments are associated with limitations, including high costs and toxicity. Several classes of natural substances have been reported to display leishmanicidal activity in the literature. Isoquinoline alkaloids, which are commonly found in the Annonaceae family, represent an important skeleton for the development of anti-leishmaniasis products. This study presents an overview of the potential use of Annonaceae alkaloids to treat leishmaniasis and describes a molecular docking study examining 215 isoquinoline alkaloids. All selected compounds contain a bisbenzyltetrahydroisoquinoline, suggesting the affinity of this skeleton for the target.

Predictive Computational Tools for Assessment of Ecotoxicological Activity of Organic Micropollutants in Various Water Sources in Brazil.

The increase of chemical pollutants detected in different aquatic environments over the past few years has been in the focus of several studies related to their occurrence, transport, fate, and hazards, or risks to human and environmental health. In Brazil, recent studies have been conducted on the occurrence of a series of organic micropollutants (OMPs) in aquatic environments. Nevertheless, the toxicological information and environmental behavior for most of these pollutants are still difficult to evaluate. We obtained consensus models using a combination of VolSurf and Dragon descriptors and Random Forest approach to predict the toxicity against Daphnia magna and Pimephales promelas for compounds identified in different sources of water in Brazil. The models showed satisfactory performance when compared with other approaches, such as Toxicity Estimation Software Tool (T.E.S.T.), etc. Both models can be used as complementary tools to aid in the prediction of organic compounds against both organisms.

Neuropharmacological effects of essential oil from the leaves of Croton conduplicatus Kunth and possible mechanisms of action involved.

ETHNOPHARMACOLOGICAL RELEVANCE: Croton conduplicatus Kunth (Euphorbiaceae) is a Brazilian aromatic medicinal plant, widely known as "quebra-faca". In folk medicine, its leaves and stem-barks are used as a natural analgesic for the treatment of headaches. AIM OF THE STUDY: In this study, we describe for the first time the neuropharmacological potential of the essential oil obtained from the leaves of Croton conduplicatus (EO) in experimental models of pain, anxiety and insomnia. The mechanisms of action involved in these activities were also investigated. MATERIAL AND METHODS: Different experimental models were used to evaluate the antinociceptive (acetic acid, formalin-induced nociception and hot plate tests), anxiolytic (elevated plus maze and hole board tests) and sedative (thiopental-induced sleeping time) effects of EO in mice. EO was evaluated in three different doses (25, 50 and 100 mg/kg, i.p.) and compared with positive and negative controls in all experimental protocols. When appropriate, animals were pretreated with pharmacological antagonists (naloxone, atropine and flumazenil) in order to evaluate the mechanisms of action involved. A docking study also was performed to identify possible targets involved. RESULTS: EO (25, 50 and 100 mg/kg, i.p.) demonstrated a significant antinociceptive activity in all experimental models. Pretreatment with naloxone or atropine reversed the antinociceptive response (p < 0.05), suggesting the involvement of opioid and muscarinic receptors, respectively. A docking study was performed with the major components identified in EO (1,8 cineole - 21.42%, spathulenol - 15.47%, p-cymene - 12.41% and caryophyllene oxide - 12.15%), demonstrating favorable interaction profile with different subtypes of muscarinic (M2, M3 and M4) and opioids (delta and mu) receptors. EO also showed anxiolytic (mainly at doses of 25 and 50 mg/kg, i.p.) and sedative (only at the dose of 100 mg/kg, i.p.) effects in mice. These pharmacological responses were reversed by flumazenil (p < 0.05), indicating possible involvement of GABAA receptors. CONCLUSION: Our findings support the traditional use of this plant as a natural analgesic and suggest that EO is a multi-target natural product, presenting not only antinociceptive effect but also anxiolytic and sedative activities depending on the dose used.

Computational Chemistry Study of Natural Alkaloids and Homemade Databank to Predict Inhibitory Potential Against Key Enzymes in Neurodegenerative Diseases.

Cissampelos sympodialis Eichl is used in folk medicine for the treatment of various inflammatory diseases; several alkaloids have been isolated from this species and some of them have anti-allergic, immunomodulatory and spasmolytic activities. Treatment of rats with the total tertiary alkaloid fraction showed an antidepressant effect. One of the depression causes can be the deficiency of monoamines, which is a factor displayed in patients with Alzheimer's disease. Theoretical studies using in silico methods have aided in the process of drug discovery. From this perspective, we applied ligand-based-virtual associated with structure-based-virtual screening of alkaloids from C. sympodialis Eichl and 101 derivatives proposed by us are promising leads against some important targets (BACE, GSK-3ß and MAO-A). From the ChEMBL database, we selected a diverse set of 724, 1898 and 1934 structures, which had been tested against BACE, GSK-3ß and MAO-A, to create Random Forest (RF) models with good overall prediction rate, over 78%, for cross-validation and test set. Compounds 24 and 47 presented activity against GSK-3ß and MAO-A simultaneously. The natural alkaloids roraimine and simpodialine-ß-N-oxide presented activity against BACE and liriodenine against MAO-A. The top 20 compounds with best docking performance per enzyme were selected and validated through the RF model. All 9 compounds classified as active in RF model for BACE are bisbenzylisoquinoline alkaloids and were present in the top docking scoring, demonstrating a consensus on results. Affinities of bisbenzylisoquinoline alkaloids, including two secondary metabolites (roraimine and simpodialine-ß-N-oxide), with BACE suggest that this skeleton can be used as a model to design new antagonists of this enzyme.

Antinociceptive Effect of the Essential Oil from Croton conduplicatus Kunth (Euphorbiaceae).

Medicinal plants have been widely used in the treatment of chronic pain. In this study, we describe the antinociceptive effect of the essential oil from Croton conduplicatus (the EO 25, 50, and 100 mg/kg, i.p.), a medicinal plant native to Brazil. Antinociceptive activity was investigated by measuring the nociception induced by acetic acid, formalin, hot plate and carrageenan. A docking study was performed with the major constituents of the EO (E-caryophyllene, caryophyllene oxide, and camphor). The EO reduced nociceptive behavior at all doses tested in the acetic acid-induced nociception test (p < 0.05). The same was observed in both phases (neurogenic and inflammatory) of the formalin test. When the hot-plate test was conducted, the EO (50 mg/kg) extended the latency time after 60 min of treatment. The EO also reduced leukocyte migration at all doses, suggesting that its antinociceptive effect involves both central and peripheral mechanisms. Pretreatment with glibenclamide and atropine reversed the antinociceptive effect of the EO on the formalin test, suggesting the involvement of KATP channels and muscarinic receptors. The docking study revealed a satisfactory interaction profile between the major components of the EO and the different muscarinic receptor subtypes (M2, M3, and M4). These results corroborate the medicinal use of C. conduplicatus in folk medicine.

Structure- and Ligand-Based Approaches to Evaluate Aporphynic Alkaloids from Annonaceae as Multi-Target Agent Against Leishmania donovani.

BACKGROUND: Leishmaniasis is a neglected disease that affects 15 million people around the world. Many limitations are associated to the treatment as high cost and toxicity. Several classes of natural substances with proven leishmanicidal activity were reported in the literature. Phytochemsitry study of Anaxagorea dolichocarpa (Annonacea) reported the isolation of aporphine alkaloids. METHODS: In this study, we evaluate the potential activity of the azaphenanthrene alkaloids eupolaramine, imbiline 1, imbiline 4, sampangine, 3-metoxisampangine and 4- metoxisampangine, isolated from A. dolichocarpa, together with a homemade databank of 142 aporphynic alkaloids isolated from Annonaceae, through ligand-based and structurebased virtual screening (VS) against Leishmania donovani. A diverse set selected from CHEMBL databank of 1397 structures, with tested antileishmanial activity against promastigote L. donovani, were classified according pIC50 values in order to generate and validate Random Forest model that show higher statistical indices values. The structure of six different L. donovani enzymes were downloaded from PDB databank and alkaloids structures were submitted to molecular docking. RESULTS: From the six azaphenanthrene alkaloids, sampangine, 3-methoxy, and 4-methoxy were indicated as potential actives by the RF model. Docking results gave similar values for all six azaphenanthrene alkaloids. So, we performed in vitro tests with sampangine, imbiline 1, imbiline 4, and eupolaramine, which are available in our laboratory, and that show significant values of pIC50 (> 5.26). CONCLUSION: Combined approach of VS allowed us to select that aporphynic alkaloid xyloguyelline as potential multitarget compound for leishmanial treatment, presenting activity against five strategic enzymes to treatment with probability of activity over 60% by RF model.

Combined structure- and ligand-based virtual screening to evaluate caulerpin analogs with potential inhibitory activity against monoamine oxidase B

Abstract Natural marine products can help increase the quality of life in patients with neurological diseases. A large number of marine products act against Alzheimer's disease through varying pathways. According to structure- and ligand-based analyses, caulerpin, an alkaloid primarily isolated from the genus Caulerpa, possesses activity against monoamine oxidase B. To predict the activity of caulerpin, we employed Volsurf descriptors and the machine learning Random Forest algorithm in parallel with a structure-based methodology that included molecular docking. Using caulerpin as a lead compound, a database containing 108 analogs was evaluated, and nine were selected as active. The structures selected as active exhibited polar and non-polar substitutions on the caulerpin skeleton, which were relevant for their activity. Dragon consensus drug-like scoring was applied to identify the active analogs that might serve as good drug candidates, and the entire group presented satisfactory performance. These results indicate the possibility of using these analogs as potential leads against Alzheimer's disease.

The antinociceptive and anti-inflammatory activities of caulerpin, a bisindole alkaloid isolated from seaweeds of the genus Caulerpa.

The antinociceptive and anti-inflammatory activity of caulerpin was investigated. This bisindole alkaloid was isolated from the lipoid extract of Caulerpa racemosa and its structure was identified by spectroscopic methods, including IR and NMR techniques. The pharmacological assays used were the writhing and the hot plate tests, the formalin-induced pain, the capsaicin-induced ear edema and the carrageenan-induced peritonitis. Caulerpin was given orally at a concentration of 100 micromol/kg. In the abdominal constriction test caulerpin showed reduction in the acetic acid-induced nociception at 0.0945 micromol (0.0103-1.0984) and for dypirone it was 0.0426 micromol (0.0092-0.1972). In the hot plate test in vivo the inhibition of nociception by caulerpin (100 micromol/kg, p.o.) was also favorable. This result suggests that this compound exhibits a central activity, without changing the motor activity (seen in the rotarod test). Caulerpin (100 micromol/kg, p.o.) reduced the formalin effects in both phases by 35.4% and 45.6%, respectively. The possible anti-inflammatory activity observed in the second phase in the formalin test of caulerpin (100 micromol/kg, p.o.) was confirmed on the capsaicin-induced ear edema model, where an inhibition of 55.8% was presented. Indeed, it was also observed in the carrageenan-induced peritonitis that caulerpin (100 micromol/kg, p.o.) exhibited anti-inflammatory activity, reducing significantly the number of recruit cells by 48.3%. Pharmacological studies are continuing in order to characterize the mechanism(s) responsible for the antinociceptive and anti-inflammatory actions and also to identify other active principles present in Caulerpa racemosa.