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Skin lesions are considered a public health problem, compromising patients' quality of life. This work aimed to evaluate the effects of fraxetin and monnieriside A on Cultured L929 Fibroblasts through the scratch assay. Supernatants and cells from the fibroblast culture treated with the compounds were used to evaluate essential markers of the tissue repair process (IGF-1, VEGF, IL-8, IL-10, FGF-2, COL1A2, COL4A, PDGF) using ELISA and qRT-PCR. The results showed that fraxetin and MOA were non-cytotoxic and could stimulate cellular migration. Fraxetin induced IGF-1, VEGF, IL-8, and IL-10 expression, while MOA induced FGF2, COL1A2, and IL-10 expression. Altogether, these results set provides evidence that fraxetin and MOA have healing potential for tissue repair, paving the way for in vivo studies and clinical trials to validate the in vitro results.
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BACKGROUND: (-)-Fenchone is a naturally occurring monoterpene found in the essential oils of Foeniculum vulgare Mill., Thuja occidentalis L., and Peumus boldus Molina. Pharmacological studies have reported its antinociceptive, antimicrobial, anti-inflammatory, antidiarrheal, and antioxidant activities. METHODS: The preventive antiulcer effects of (-)-Fenchone were assessed through oral pretreatment in cysteamine-induced duodenal lesion models. Gastric healing, the underlying mechanisms, and toxicity after repeated doses were evaluated using the acetic acid-induced gastric ulcer rat model with oral treatment administered for 14 days. RESULTS: In the cysteamine-induced duodenal ulcer model, fenchone (37.5-300 mg/kg) significantly decreased the ulcer area and prevented lesion formation. In the acetic acid-induced ulcer model, fenchone (150 mg/kg) reduced (p < 0.001) ulcerative injury. These effects were associated with increased levels of reduced glutathione (GSH), superoxide dismutase (SOD), interleukin (IL)-10, and transforming growth factor-beta (TGF-ß). Furthermore, treatment with (-)-Fenchone (150 mg/kg) significantly reduced (p < 0.001) malondialdehyde (MDA), myeloperoxidase (MPO), interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and nuclear transcription factor kappa B (NF-κB). A 14-day oral toxicity investigation revealed no alterations in heart, liver, spleen, or kidney weight, nor in the biochemical and hematological parameters assessed. (-)-Fenchone protected animals from body weight loss while maintaining feed and water intake. CONCLUSION: (-)-Fenchone exhibits low toxicity, prevents duodenal ulcers, and enhances gastric healing activities. Antioxidant and immunomodulatory properties appear to be involved in its therapeutic effects.
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Mosquitoes of the Aedes genus are responsible for transmitting many vector-borne viral diseases worldwide. Hundreds of thousands of people die annually from vector-borne diseases, including West Nile fever, dengue, tick-borne diseases, yellow fever, chikungunya, Rift Valley fever, and Zika. Billions of people are at the risk of infection on all continents, which is a cause of international concern. Therefore, new vector-control methods are essential for mitigating these illnesses. The bioactive hydrocarbons isolated from Xylopia langsdorfiana St. Hilaire & Tulasne are trachylobanes, a rare class of diterpenes found in the n-hexane fraction of the stem and leaf ethanolic extracts. These were tested against Ae. aegypti fourth-instar larvae over 48 h of exposure, with LC50 values ranging from 19.84 to 72.9 µg/mL, comparable to that of the positive control. The findings highlight the potential of Xylopia langsdorfiana St. Hilaire & Tulasne metabolites for controlling the main vectors of arthropod-borne viruses.
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ETHNOPHARMACOLOGICAL RELEVANCE: Ayahuasca (AYA) is a psychedelic brew used in religious ceremonies. It is broadly used as a sacred medicine for treating several ailments, including pain of various origins. AIM OF THE STUDY: To investigate the antinociceptive effects of AYA and its mechanisms in preclinical models of acute and chronic pain in mice, in particular during experimental neuropathy. MATERIALS AND METHODS: The antinociceptive effects of AYA administered orally were assessed in the following models of pain: formalin test, Complete Freund's Adjuvant (CFA)-induced inflammation, tail flick test, and partial sciatic nerve ligation model of neuropathic pain. Antagonism assays and Fos immunohistochemistry in the brain were performed. AYA-induced toxicity was investigated. AYA was chemically characterized. The antinociceptive effect of harmine, the major component present in AYA, was investigated. RESULTS: AYA (24-3000 µL/kg) dose-dependently reduced formalin-induced pain-like behaviors and CFA-induced mechanical allodynia but did not affect CFA-induced paw edema or tail flick latency. During experimental neuropathy, single treatments with AYA (24-3000 µL/kg) reduced mechanical allodynia; daily treatments once or twice a day for 14 days promoted consistent and sustained antinociception. The antinociceptive effect of AYA (600 µL/kg) was reverted by bicuculline (1 mg/kg) and methysergide (5 mg/kg), but not by naloxone (5 mg/kg), phaclofen (2 mg/kg), and rimonabant (10 mg/kg), suggesting the roles of GABAA and serotonergic receptors. AYA increased Fos expression in the ventrolateral periaqueductal gray and nucleus raphe magnus after 1 h, but not after 6 h or 14 days of daily treatments. AYA (600 µL/kg) twice a day for 14 days did not alter mice's motor function, spontaneous locomotion, body weight, food and water intake, hematological, biochemical, and histopathological parameters. Harmine (3.5 mg/kg) promoted consistent antinociception during experimental neuropathy. CONCLUSIONS: AYA promotes consistent antinociceptive effects in different mouse models of pain without inducing detectable toxic effects. Harmine is at least partially accountable for the antinociceptive properties of AYA.
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Banisteriopsis , Dolor Crónico , Neuralgia , Ratones , Animales , Dolor Crónico/tratamiento farmacológico , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/inducido químicamente , Harmina/efectos adversos , Analgésicos/efectos adversos , Neuralgia/tratamiento farmacológico , Modelos Animales de EnfermedadRESUMEN
The dual inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) is considered as an important strategy for the treatment of Alzheimer's disease. In this study, we applied the bioguided fractionations of Ocotea daphinifolia ethyl acetate active extract to furnish a fraction with high inhibitory activity for AChE and BuChE (82% and 92%, respectively). High-performance liquid chromatography semipreparative purification of this fraction provided two new natural products: 1-ß-D-galactopyranosyl-glycerol-2,3-heptanedionate, (1) whose complete chemical structural elucidation was made with spectrometric analysis (MS, 1D, and 2D NMR) and its minor derivative 1-ß-D-gulopyranosyl-glycerol-2,3-heptanedionate; (2) which could be characterized by 2D 1 H-13 C heteronuclear single-quantum correlation spectra analysis. Investigation of the intermolecular interactions with cholinesterases was carried out by molecular docking studies, and results suggested that both compounds are capable to interact with the catalytic site of both enzymes. Compounds 1 and 2 interact with residues of catalytic domains and the peripheral anionic binding site of AChE and BuChE. The results are comparable to those achieved with rivastigmine and galantamine. Thus, this study provides evidence for consideration of the glycosylglycerol from O. daphnifolia as new valuable dual cholinesterases inhibitor.
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Enfermedad de Alzheimer , Ocotea , Inhibidores de la Colinesterasa/química , Butirilcolinesterasa/química , Simulación del Acoplamiento Molecular , Acetilcolinesterasa/metabolismo , Ocotea/metabolismo , Glicerol , Espectroscopía de Resonancia MagnéticaRESUMEN
Plants of Hyptidinae subtribe (Lamiaceae - family), as Mesosphaerum sidifolium, are a source of bioactive molecules. In the search for new drug candidates, we perform chemical characterization of diterpenes isolated from the aerial parts of M. sidifolium was carried out with uni- and bidimensional NMR spectral data, and evaluate in silico through the construction of a predictive model followed by in vitro testing Mycobacterium tuberculosis and Mycobacterium smegmatis. Resulted in the isolation of four components: Pomiferin D (1), Salviol (2), Pomiferin E (3) and 2α-hydroxysugiol (4), as well as two phenolic compounds, rosmarinic and caffeic acids. In silico model identified 48 diterpenes likely to have biological activity against M. tuberculosis. The diterpenes isolated were tested in vitro against M. tuberculosis demonstrating MIC = 125 µM for 4 and 1, while 2 and 3 -MIC = 250 µM. These compounds did not show biological activity at these concentrations for M. smegmatis.
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Diterpenos , Lamiaceae , Mycobacterium tuberculosis , Tuberculosis , Pruebas de Sensibilidad Microbiana , Diterpenos/química , Lamiaceae/química , Antituberculosos/químicaRESUMEN
A new nor-ent-kaurene diterpene and ten other compounds were isolated from Annona vepretorum stems, including four kaurene diterpenes, three alkamides, one sesquiterpene and two steroids. Their chemical structures were elucidated using spectroscopic methods, including 1D-, 2D-NMR, and HRESIMS. The absolute configuration of compounds 1, 5, 8, 9 and 10 was confirmed by CD experiments. Compounds 1-5 and 8-10 were evaluated for cytotoxic activity using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT method, against three human carcinoma cell lines: human colon (HCT-116), glioblastoma (SF295) and prostate (PC3). However, all isolated compounds exhibited low cytotoxic activity.
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Annona , Annonaceae , Diterpenos de Tipo Kaurano , Diterpenos , Masculino , Humanos , Annona/química , Diterpenos de Tipo Kaurano/química , Diterpenos/química , Extractos Vegetales/químicaRESUMEN
This review of the current literature aims to study correlations between the chemical structure and gastric anti-ulcer activity of tannins. Tannins are used in medicine primarily because of their astringent properties. These properties are due to the fact that tannins react with the tissue proteins with which they come into contact. In gastric ulcers, this tannin-protein complex layer protects the stomach by promoting greater resistance to chemical and mechanical injury or irritation. Moreover, in several experimental models of gastric ulcer, tannins have been shown to present antioxidant activity, promote tissue repair, exhibit anti Helicobacter pylori effects, and they are involved in gastrointestinal tract anti-inflammatory processes. The presence of tannins explains the anti-ulcer effects of many natural products.
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Antiulcerosos/farmacología , Úlcera Péptica/prevención & control , Taninos/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Antiulcerosos/química , Infecciones por Helicobacter/etiología , Infecciones por Helicobacter/fisiopatología , Infecciones por Helicobacter/prevención & control , Helicobacter pylori/efectos de los fármacos , Humanos , Úlcera Péptica/etiología , Úlcera Péptica/fisiopatología , Fitoquímicos/química , Fitoquímicos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Relación Estructura-Actividad , Taninos/químicaRESUMEN
Aplysina is the best representative genus of the family Aplysinidae. Halogenated substances are its main class of metabolites. These substances contribute greatly to the chemotaxonomy and characterization of the sponges belonging to this genus. Due to their pharmacological activities, these alkaloids are of special interest. The chemistry of halogenated substances and of the alkaloids has long been extensively studied in terrestrial organisms, while the number of marine organisms studied has just started to increase in the last decades. This review describes 101 halogenated substances from 14 species of Aplysina from different parts of the world. These substances can be divided into the following classes: bromotyramines (A), cavernicolins (B), hydroverongiaquinols (C), bromotyrosineketals (D), bromotyrosine lactone derivatives (E), oxazolidones (F), spiroisoxazolines (G), verongiabenzenoids (H), verongiaquinols (I), and dibromocyclohexadienes (J). A compilation of their (13)C NMR data is also part of the review. For this purpose 138 references were consulted.
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Compuestos de Bromina/química , Espectroscopía de Resonancia Magnética , Poríferos/química , Alcaloides/química , Alcaloides/aislamiento & purificación , Animales , Compuestos de Bromina/aislamiento & purificación , Isótopos de Carbono , HalogenaciónRESUMEN
Tissue damage due to oxidative stress is directly linked to development of many, if not all, human morbidity factors and chronic diseases. In this context, the search for dietary natural occurring molecules with antioxidant activity, such as flavonoids, has become essential. In this study, we investigated a set of 41 flavonoids (23 flavones and 18 flavonols) analyzing their structures and biological antioxidant activity. The experimental data were submitted to a QSAR (quantitative structure-activity relationships) study. NMR 13C data were used to perform a Kohonen self-organizing map study, analyzing the weight that each carbon has in the activity. Additionally, we performed MLR (multilinear regression) using GA (genetic algorithms) and molecular descriptors to analyze the role that specific carbons and substitutions play in the activity.
Danos aos tecidos devido ao estresse oxidativo estão diretamente ligados ao desenvolvimento de muitos, senão todos, os fatores de sedentarismo e de doenças crônicas. Neste contexto, a busca de moléculas naturais, que participam da nossa dieta e que possuam atividade antioxidante, flavonóides, torna-se de grande interesse. Neste estudo, nós investigamos um conjunto de 41 flavonóides (23 flavonas e 18 flavonóis), relacionando suas estruturas e atividade antioxidante. Os dados experimentais foram submetidos à análise de QSAR (relações quantitativas estrutura-atividade). Dados de RMN 13C foram utilizados para realizar um estudo do mapa auto-organizável de Kohonen, analisando o peso que cada carbono tem na atividade. Além disso, realizamos uma MLR (regressão múltipla) usando GA (algoritmos genéticos) e descritores moleculares para avaliar a influência de carbonos e substituições na atividade.
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Antioxidantes/química , Espectroscopía de Resonancia Magnética/métodos , Flavonoides/análisis , Flavonoides/química , Relación Estructura-Actividad , Flavonas/análisis , Flavonas/química , Flavonoles/análisis , Flavonoles/química , Estructura MolecularRESUMEN
Aldose Reductase (AR) is the polyol pathway key enzyme which converts glucose to sorbitol. High glucose availability in insulin resistant tissues in diabetes leads into an accumulation of sorbitol, which has been associated with typical chronic complications of this disease, such as neuropathy, nephropathy and retinopathy. In this study, 71 flavonoids AR inhibitors were subjected to two methods of SAR to verify crucial substituents. The first method used the PCA (Principal Component Analysis) to elucidate physical and chemical characteristics in the molecules that would be essential for the activity, employing VolSurf descriptors. The rate obtained explained 53 percent of the system total variance and revealed that a hydrophobic-hydrophilic balance in the molecules is required, since very polar or nonpolar substituents decrease the activity. Artificial Neural Networks (ANNs) was also employed to determine key substituents by evaluating substitution patterns, using NMR data. This study had a high success rate (85 percent accuracy in the training set and 88 percent accuracy in the test set) and showed polihydroxilations are essential for high activity and methoxylations and glicosilations primarily at positions C7, C3' and C4' decrease the activity.
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Natural products have widespread biological activities, including inhibition of mitochondrial enzyme systems. Some of these activities, for example cytotoxicity, may be the result of alteration of cellular bioenergetics. Based on previous computer-aided drug design (CADD) studies and considering reported data on structure-activity relationships (SAR), an assumption regarding the mechanism of action of natural products against parasitic infections involves the NADH-oxidase inhibition. In this study, chemometric tools, such as: Principal Component Analysis (PCA), Consensus PCA (CPCA), and partial least squares regression (PLS), were applied to a set of forty natural compounds, acting as NADH-oxidase inhibitors. The calculations were performed using the VolSurf+ program. The formalisms employed generated good exploratory and predictive results. The independent variables or descriptors having a hydrophobic profile were strongly correlated to the biological data.
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Complejos Multienzimáticos/antagonistas & inhibidores , NADH NADPH Oxidorreductasas/antagonistas & inhibidores , Proteínas Protozoarias/antagonistas & inhibidores , Trypanosoma cruzi/enzimología , Animales , Productos Biológicos/química , Productos Biológicos/uso terapéutico , Enfermedad de Chagas/tratamiento farmacológico , Flavonoides/química , Flavonoides/uso terapéutico , Humanos , Modelos Moleculares , Estructura Molecular , Relación Estructura-Actividad CuantitativaRESUMEN
Maytenus obtusifolia é utilizada na medicina popular para o tratamento de úlceras graves, inflamações gerais e câncer. Apesar da importância etnofarmacológica desta espécie, nenhum estudo foi realizado para avaliar a sua toxicidade e atividade antiulcerogênica. Neste estudo, nós avaliamos a toxicidade e propriedade antiulcera do extrato etanólico das folhas de Maytenus obtusifolia (MO-EtOH). O MO-EtOH (10-1000 µg/mL) mostrou baixa toxicidade para as larvas de A. salina com CL50 maior que 1000 µg/mL. O MO-EtOH (2000 mg/kg, p.o.) nγo alterou o peso corporal e peso dos órgãos dos camundongos, mas foi observado um aumento no consumo de água dos machos e uma diminuição do consumo alimentar das fêmeas. Durante o estudo não foram observadas mortes e nem alterações macroscópicas nos órgãos dos camundongos. MO-EtOH (62,5, 125, 250 e 500 mg/kg) e lansoprazol (30 mg/kg) reduziram significativamente o índice ulcerativo para 65,58 ± 8,74, 43,00 ± 9,53, 15,50 ± 7,56, 54,75 ± 8,88 e 36,13 ± 9,55, respectivamente, em comparação com salina 82,13 ± 12,48. Em conclusão, o MO-EtOH apresentou baixa toxicidade e atividade antiulcerogênica, o que confirma o uso popular de M. obtusifolia.
Maytenus obtusifolia is used in folk medicine for the treatment of serious ulcers, general inflammations and cancer. Despite of the ethnopharmacological importance of this species, no study was conducted to evaluate its toxicity and antiulcerogenic activity. In this study, we evaluated the toxicity and antiulcerogenic property of the ethanol extract of the leaves of Maytenus obtusifolia (MO-EtOH). The MO-EtOH (10-1000 µg/mL) showed low toxicity for larvae of A. salina with LC50 higher than 1000 µg/mL. The MO-EtOH (2000 mg/kg, p.o.) did not change the body and organs weight of the mice, but it was observed an increase in the water consumption of males and a decrease in the food consumption of females. During the study no deaths and no macroscopic changes in the organs were observed in the mice. MO-EtOH (62.5, 125, 250 and 500 mg/kg) and lansoprazole (30 mg/kg) significantly reduced the ulcerative index for 65.58 ± 8.74, 43.00 ± 9.53, 15.50 ± 7.56, 54.75 ± 8.88 and 36.13 ± 9.55, respectively, in comparison with saline 82.13 ± 12.48. In conclusion, the MO-EtOH showed low toxicity and antiulcerogenic activity, confirming the popular use of M. obtusifolia.
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O óleo essencial das folhasde Rollinia leptopetala foi obtido por hidrodestilação em aparelho de Clevenger e a sua composição química foi analisada através de CG-EM. Com essa técnica, foi possível identificar 22 constituintes em uma mistura complexa demonoterpenos (54,5 por cento) e sesquiterpenos (45,5 por cento). O principal componente encontradonas folhas foi o biciclogermacreno (22,47 por cento). O óleo essencial foi avaliado numa linhagem de Staphylococcus aureus portadora de bomba de efluxo responsável pela resistência norfloxacino. Embora o óleo essencial não tenha apresentado atividade antibacteriana relevante in vitro, ele apresentou atividade moduladora da resistência, ou seja, em combinação com o norfloxacino observou-se uma redução de 4x na concentração inibitória mínima do antibiótico, indicando inibição de bomba de efluxo.
The essential oil from the leaves of Rollinia leptopetala was obtained by hydrodistillation in Clevenger's apparatus and its chemical composition was analyzed by GC-MS. With this technique could be identified 22 constituents in a complex mixture of monoterpenes (54.5 percent) and sesquiterpenes (45.5 percent). The main component found in the leaves was the bicyclogermacrene (22.47 percent). The essential oil was assayed against a strain of Staphylococcus aureus possessing efflux mechanism of resistance to norfloxacin. Although the essential oil did not display relevant antibacterial activity in vitro, it modulated the activity of the norfloxacin, i.e. in combination with the antibiotic it was observed a fourfold reduction in the minimum inhibitory concentration for norfloxacin, indicating inhibition of efflux pump.
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A família Aristolochiaceae apresenta entre seus constituintes terpenóides, alcalóides e lignóides. Papo-de-peru, jarrinha, mil-homens e capivara são nomes populares da espécie Aristolochia birostris, a qual é utilizada na medicina popular como antiofídica, sudorífica, anticatarral e abortiva. Um estudo fitoquímico anterior com as partes aéreas desta espécie reportou o isolamento de quatro terpenóides, um lignóide e uma antraquinona. Dando continuidade a esse estudo, este trabalho relata a identificação de 4 lignóides, sendo dois do tipo ariloxiarilpropânico (4-metilenodioxi-5,3',5' -trimetoxi-1'-alil-8.O.4'-neolignana e 3,4,5,3',5'-pentametoxi-1'-alil-8.O.4'-neolignana), um do tipo tetraidrofurano (grandisina) e uma lignana dibenzilbutirolactônica [(-)-hinoquinina], além de vanilina. As estruturas foram estabelecidas através de métodos espectroscópicos de infravermelho e ressonância magnética nuclear uni e bidimensionais. Os lignóides foram avaliados quanto a atividade antimicrobiana frente a algumas cepas de bactérias, fungos e leveduras, entretanto foram inativos.
The family Aristolochiaceae presents among its chemical constituents terpenoids, alkaloids and lignoids. Aristolochia birostris is a species of this family popularly known as "papo-de-peru", "jarrinha", "mil-homens" and "capivara", and it is used in the folk medicine to treat snake bites, as a sudorific, expectorant and abortive. A previous phytochemical study of the aerial parts of this plant reported the isolation of four terpenoids, lignoids and antraquinone. Continuing this study it is now reported the isolation of four lignoids, two of the type aryloxyarylpropane (4-methylenedioxy-5,3',5'-trimethoxy-1'-alyl-8.O.4' -neolignan and 3,4,5,3',5'-pentamethoxy-1'-alyl-8.O.4'-neolignan), one tetrahydrofuran (grandisin) and a dibenzylbutyrolactone lignans [(-)-hinokinin], and also vanillin. The chemical structures of the isolated compounds were established based on spectral data, mainly IR and NMR including 1D and 2D experiments. The lignoids were evaluated for their activity against some bacteria (Staphylococcus epidermidis, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus faecalis and Escherichia coli), fungi (Aspergilus flavus and Microsporum canis) and yeast (Candida albicans, Candida tropicalis and Criptococcus neoformans), but they were inactive.
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Arrabidaea harleyi A.H. Gentry (Bignoniaceae) is an ornamental plant found in some regions of the Atlanticforest in Brazil. From its bark a mixture of verbascoside and isoverbascoside was isolated. This mixture was shown to be active against Staphylococcus aureus, Micrococcus luteus, Bacillus subtilis, Bacillus mycoides, Enterecoccus faecalis, Escherichia coli, Serratia marcensis and Candida albicans. The minimal inhibitory concentration (MIC) was established by diffusion method
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Farmacognosia , Plantas Medicinales , Extractos Vegetales , Tallos de la PlantaRESUMEN
Phytochemical investigation of the aerial parts of S. paludosum afforded 3,4,7,8-tetramethyl gossypetinr, 3,7- dimethyl kaempferol, 3-methyl kaempferol, 3-methyl apigenin, and 3-methyl quercetin ethers, besides N-p-transcoumaroyltiramine, and protocatecuid acid. The structures were established from spectral data of the natural substances and the permethyl and acetyl derivatives of tetramethyl gossypetin.
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Neste trabalho foi verificado o teor de Óleos, sólidos e bixina em sementes de quatro variedades de Bixa orellana L. cultivadas na Paraíba: "Casca verde", "Casca vermelha", Bico de calango" e "Grão preto". Os melhores resultados foram obtidos com os tipos "Casca verde" e "Casca vermelha" que apresentaram um rendimento em bixina pura, cristalina, de 1,3 e 1,1 por cento, respectivamente.
In this work it was verified the content of oils, solids and bixin in seeds of four varieties of Bixa orellana L. cultivated in Paraíba: "Casca verde", "Casca vermelha", Bico de calango" and "Grão preto". The best results were obtained with the types "Casca verde" and "Casca vermelha" that presented an yield in pure, crystalline bixina, of 1,3 and 1,1 percent, respectively.